Ocular drug delivery

tSolid lipid nanoparticles (SLN) composed of long-chain fatty acids (palmitic acid, stearic acid or arachidicacid), Epikuron 200 (purified phosphatidylcholine), and bile salts (cholate, taurocholate or taurodeoxy-cholate) have been prepared by dilution of a microemulsion. A total of five different systems wereprepared, and characterized by photon correlation spectroscopy, transmission electron microscopy,differential scanning calorimetry, and infrared spectroscopy. The SLN formulation showing optimal prop-erties (lowest size and polydispersity index and highest zeta potential) was obtained with stearic acidand taurodeoxycholate as cosurfactant. This formulation was loaded with Calendula officinalis extract, anatural compound used on ophthalmic formulations given its anti-inflammatory, emollient, and woundrepairing activity. Calendula-loaded SLN preparations were characterized in order to determine loadingcapacity and entrapment efficiency. In vitro cytotoxicity and wound healing efficacy of Calendula-loadedSLN compared to that of a free plant extract were evaluated on a conjunctival epithelium cell line WKD.Our results suggest that this SLN formulation is a safe and solvent-free Calendula extract delivery sys-tem which could provide a controlled therapeutic alternative for reducing disease-related symptoms andimproving epithelium repair in ocular surface.

This article is a discussion to the question, "what are the different methods of preparing conventional ocular drug delivery system, its major setbacks and steps to overcome those setbacks?"The answer to this kind of question takes the route of lengthy research processes and gives the outcomes in the form of advancement of techniques in ophthalmic drug delivery system. In -situ-gel, Ocusert, Osmotic minipumps, Implants, Ocufit, NODS (new ophthalmic delivery system) and gene delivery are some of the examples of recent advancements in the field of ocular drug delivery system. Now a days above mentioned formulations are playing a significant role in the treatment of anterior and posterior segment of eye diseases .This review also helps to select the 'drugs and polymer combinations' while formulating inserts.

Ocular drug delivery system for the treatment of eye diseases has become popular and feasible in the past few years. Improving ocular contact time, enhancing corneal permeability and site specificity are the key points for the optimization of ocular drug delivery. Use of polymers such as ethylene vinyl acetate copolymer can increase the solution viscosity and decrease the drainage of solution, thereby increasing the contact time and its bioavailabilty. There are various types of ocular drug release system such as ocusert, contact lenses, diffusional inserts which falls under the category of non-erodible ocular controlled release system, lacrisert, soluble ocular delivery implant(SODI), minidisc which falls under the category of erodible ocular controlled release system; nanoparticles; liposomes.
Episcleral, intrascleral and suprachoroidal routes have the advantage of bypassing the main barriers to topical drug penetration. This type of delivery system provides a controlled release of drug for a long period of time. This type of delivery system has good patient compliance. Acuvue, lacrisert; biomedics are the most common marketed products of ocular drug delivery system.
This manuscript will review the recent research advances on ocular drug delivery system and their types.
Keywords: ocular drug delivery system, bioavailability, ethylene vinyl acetate copolymer; episcleral, intrascleral and suprachoroidal routes of drug delivery; erodible and non erodible ocular controlled release system.

The main objective of this study was to assess awareness of danger
signs of pregnancy and its associated factors in Mekelle public
hospitals, 2014.
Institutional based cross sectional study was conducted among 422
pregnant mothers. Data was collected using interviewer administered
questionnaire; it was entered and analyzed using SPSS version 16.
The data were presented using texts, graphs and tables.
Out of the total participants of this study 79.6% mothers had
information about danger signs of pregnancy from which 61.9%
mothers had information about vaginal bleeding followed by sudden
gush of fluid before labor which was mentioned by 41.9% of
respondents. Severe unusual abdominal pain was the least known
danger signs as mentioned by 19 % of mothers. The main source of
information for the danger signs was health personnel and
Negligence was the main reason for not having good awareness about
danger signs of pregnancy.
Therefore, health extension workers should strengthen their
awareness creation activities; community mobilization and health
education should be considered with policy makers and other
interested organizations.

The current study sought to formulate, optimize, and evaluate curcumin-loaded Nanostructured Lipid Carriers (NLCs) for their in vitro and ex vivo characteristics. NLCs, prepared using hot-melt emulsification and ultrasonication techniques, were optimized using a Central Composite Design (CCD) and evaluated for their in vitro physicochemical characteristics. Their stability over a 3 month period and transcorneal permeation across excised rabbit corneas (ex vivo) were assessed for the optimized NLCs. The optimized NLC, with a particle size of 66.8 ± 2 nm, polydispersity index of 0.17 ± 0.05, entrapment efficiency of 96 ± 1.6%, and drug loading of 3.1 ± 0.05% w/w, was chosen using CCD. The optimized NLCs showed optimum ex vivo stability at 4 °C for the study period and demonstrated a significant increase in curcumin permeation (∼2.5-fold) across the rabbit cornea in comparison to the control. Overall, these studies indicated the successful development of NLCs using the design of experiment approach; the formulation enhanced curcumin permeation across excised corneas and did not show any harmful side effects.

oligonucleotides have predominant role in its delivery for various
diseases. Objective: Antisense compounds are biological
molecules consisting of small ribonucleic acid (RNA) or
deoxyribonucleic acid (DNA) segments (Oligonucleotide) which
have enormous potential for the treatment of number of diseases.
Methods: All the methods analyzed were obtained through high
impact articles. Results: Several impediments were made to
Oligonucleotide for its widespread usage as them as drugs to
overcome their lack of stability in physiological fluids and their
poor penetration into cells. Experiments like, association with or
encapsulation within nano-and micro sized drug delivery systems,
lipids and polymers could help to increase the efficiency of
oligonucleotide delivery. This review discusses the use of cationic
lipids, Cell penetrating peptides, nanoparticles, microparticles and
several novel methods that have recently been explored as delivery
vehicles. Conclusion: The use of naked Oligonucleotide given a
clear cut way to new targets for potential therapeutic compounds.
Apart this, antisense therapy represents a promising and evolving
approach to the management of numerous diseases in which a
specific abnormality has been identified as a primary or major
contributing etiologic factor. In near future, authors strongly
believe that antisense therapy will give a positive way for number
of In vitro experiments and break through for many life
threatening diseases.

Currently, natamycin ophthalmic suspension (Natacyn ®) is the only commercially available antifungal agent that has been approved in the treatment of superficial fungal infections of the eye such as fungal keratitis, blepharitis, and conjunctivitis. Despite natamycin requiring frequent application due to low retention at the ocular surface, it has shown efficacy in treating superficial ophthalmic fungal infections. This is attributed to its broad antifungal spectrum against filamentous fungi, safety profile, and its trans-corneal penetration capability. The ability of natamycin to traverse across the intact cornea and reach adjacent stromal layers has been credited to be one of the major factors favoring its continued use in superficial fungal infections over other antifungal agents such amphotericin B and azole class of anti-fungals, which can only penetrate the debrided cornea, but not intact cornea, to elicit their activity. This has led to natamycin being one of the front-line agents in the therapy of superficial ocular fungal infections. This review discusses various aspects of natamycin such as its chemistry and pharmacology, antifungal spectrum and potential for development of resistance, ocular clinical evaluations, and specifics on the marketed natamycin formulation (Natacyn ®) to obtain a perspective of natamycin use in ophthalmic fungal infections.

The present work was aimed to design & characterize an oral dosage form to release Terbutaline sulphate following a programmed time period (pulsed release system). Pulsatile release tablet comprises a drug containing core and pH sensitive polymeric coating capable of delaying drug release and providing gastric resistance .The core tablets of terbutaline sulphate were prepared for the treatment of nocturnal asthma .The core tablets were prepared by direct compression method using different disintegrating agents. The cores were coated with pH sensitive polymers (Eudragit S-100, Eudragit L-100) at different coating levels to develop a suitable dosage form which should show minimum drug release in upper regions of gastrointestinal tract (GIT). Prepared tablets were characterized for various physical parameters such as hardness, thickness, weight variation disintegration test drug content and in-vitro drug release characteristics. All the parameters were found to be in the standard range. The dissolution of best formulation F 4 S 3 , F 7 S 3 and F 11 S 3 have shown the lag phase of 5 hrs at 10% coating level and almost complete drug release was achieved after 11 hrs . The kinetic study data for best formulation followed zero order kinetics. Stability study of the best formulation indicates no significant difference in release profile after a period of 3 months.

The objective of the research was firstly to investigate the behavior of Surelease (release retardant binder) alone and in combination with other hydrophilic polymers on the release of zidovudine from sustained release matrix tablet. Secondly, to compare between the release pattern of polyethylene oxide and Methocel K100M alone and in combination. A randomized surface methodology (RSM) was applied to study the effect of polymers on drug release. The independent variables of the formulation were: the type of polymers (X1), concentration of polymers (X2) in the tablet and dependent variables are the percentage drug release at 2 hours (Y1) and the percentage drug release at 12 hours (Y 2 ). Release kinetics were analyzed using zero-order, first order, higuchi's square root and korsmeyer-peppas empirical equations in terms of r 2 . Results of invitro drug release kinetics study suggests that, all formulations follows zero order kinetics with r 2 value in range of 0.99 and fitting the release data to korsmeyers equation release exponent n ranged from 0.83 to 1.22 and followed non-Fickian diffusion mechanism (anomalous transport) and super case II transport for Surelease formulations. Among all the formulations, F14 matrix tablet containing combination of Surelease and polyoxWSR301 shows 102.37% of drug release at the end of 12 hours.

Febuxostat is a urate lowering drug, an inhibitor of xanthine
oxidase used in the treatment of hyperuricemia and chronic gout. The
drug shows dissolution-rate limited absorption, there by poor and
variable bioavailability. It needs enhancement in bioavailability to
derive maximum therapeutic efficacy. The main objective of the
present research work is to enhance the solubility and dissolution rate
of Febuxostat by preparing the Spherical agglomerates. Spherical
agglomerates were prepared by the quasi emulsion solvent diffusion
method. N, N-dimethyl form amide, chloroform and water were
selected as good solvent, bridging liquid and poor solvents
respectively. Polyethylene glycol, Poloxomer- F68 and Polyvinyl
alcohol were used as a carrier. Among all the formulations prepared,
spherical agglomerates prepared with Febuxostat and Poloxomer-
F68 in 1:1 ratio showed highest drug release in 60 minutes. Spherical
agglomerates prepared with Febuxostat and Poloxomer- F68 in 1:1
ratio was used in the preparation of orodispersible tablets. To study
the influence of superdisintegrants on performance of Febuxostat
Orodispersible Tablets, a set of three formulations (K1, K2, K3) were
prepared using three superdisintegrants sodium starch glycolate,
Croscarmalose sodium and Crospovidone . The orodispersible tablets
of Febuxostat prepared with Crospovidone showed rapid drug release
when compared to pure drug and other tablet formulations.

The present study was aimed to formulate and evaluate fast
dissolving oral films of Zolmitriptan using sodium alginate, xanthan
gum and sodium starch glycolate, guar gum. The suitable plasticizer
and its concentration were selected on the basis of flexibility, tensile
strength and stickiness of the film. The films are prepared by solvent
casting method and characterized by UV, FTIR studies. The films
were evaluated for disintegration time, Folding endurance, Tensile
Strength, Mouth dissolving time, Thickness, content uniformity and
In-vitro dissolution studies. The F5 formulation has given 98.5% drug
release within 6 minutes and has a tensile strength of 1.80 MPa.

The current study was aimed to develop the meclizine hydrochloride
sublimated fast dissolving tablets using different sublimated agents to
enhance the dissolution rate. The prepared fast dissolving tablets
were subjected to pre-compression properties and characterized for
hardness, weight variation, friability, wetting time, water absorption
ratio, and disintegration time. From In vitro dissolution studies, the
formulation F3 containing camphor (10%w/w) as the sublimating
agent showed rapid dissolution of about 98.61% in 30 min, and
disintegration time 43 sec when compared with other sublimating
agents. The percent drug release in 30 min (Q30) and initial
dissolution rate for formulation F3 was 98.61±0.25%, 3.29%/min.
These were very much higher compared to marketed tablets
(65.43±0.57%, 2.18%/min). The dissolution efficiency was found to
be 63.37 and it is increased by 1.4 fold with F3 FDT tablets
compared to marketed tablets. Differential scanning calorimetry and
Fourier transform infrared spectroscopy studies revealed that there
was no possibility of interactions. In conclusion, development of
meclizine hydrochloride fast dissolving tablets by sublimation
method is an appropriate method to enhance the dissolution rate.

Background: A Dyop (or dynamic optotype) is a spinning visual target which uses the strobic detection of the spinning gaps/segments of the ring to measure visual acuity. Methods: Forty subjects with visual acuity better than 6/12 (20/40) and ages between 20 and 28 years (24.48 ± 2.01 years) were recruited at the University of Benin Optometry Clinic. Snellen and Dyop acuity charts were displayed on a monitor at a distance of 6 meters. The assessment sequence between the two acuity chart formats was alternated for every other patient to reduce potential refractionist bias. Subjective refraction was measured in both eyes, and the duration of testing for each patient and each method was recorded. Results: There was no significant mean Thibos notations difference, M (p = 0.77), J0 (p = 0.27), and J45 (p = 0.57) using the Bland-Altman plot and 95% limits of agreement between the two charts, and there were no differences as to age or gender. There was, however, a disparity in the mean acuity of about 0.25 diopters with the mean Snellen acuity of 1.60 ± 0.21 decimal units and the mean Dyop acuity of 1.17 ± 0.14 decimal units with a linear relationship: y = 0.3121x + 0.6709 (p = 0.00). The refraction with a Dyop acuity chart also typically took half as long (339 ± 122 seconds) as the refraction with a Snellen acuity chart (680 ± 281 seconds), p = 0.00.

Poor ocular bioavailability of drugs (b1%) from conventional eye drops (ie, solution, suspension, and ointments) is mainly due to the physiologic barriers of the eye. In general, ocular efficacy is closely related to ocular drug bioavailability, which may be enhanced by increasing corneal drug penetration and prolonging precorneal drug residence time. In our current work, we develop and evaluate a new colloidal system, that is, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles for sparfloxacin ophthalmic delivery, to improve precorneal residence time and ocular penetration. Nanoparticles were prepared by nanoprecipitation technique and characterized for various properties such as particle size, zeta potential, in vitro drug release, statistical model fitting, stability, and so forth. Microbiological assay was carried out against Pseudomonas aeruginosa using the cup-plate method. Precorneal residence time was studied in albino rabbits by gamma scintigraphy after radiolabeling of sparfloxacin by Tc-99m. Ocular tolerance of the developed nanosuspension was also studied by the Hen Egg Test-Chorioallantoic Membrane (HET-CAM) method. The developed nanosuspension showed a mean particle size in the range of 180 to 190 nm, suitable for ophthalmic application with zeta potential of -22 mV. In vitro release from the developed nanosuspension showed an extended release profile of sparfloxacin according to the Peppas model. Acquired gamma camera images showed good retention over the entire precorneal area for the developed nanosuspension compared with that of a marketed formulation. The marketed drug formulation cleared very rapidly from the corneal region and reached the systemic circulation through the nasolacrimal drainage system, as significant radioactivity was recorded in kidney and bladder after 6 hours of ocular administration, whereas the developed nanosuspension cleared at a very slow rate (P b .05) and remained at the corneal surface for longer duration, as no radioactivity was observed in the systemic circulation. HET-CAM assay with 0 score in 8 hours indicates the nonirritant property of the developed nanosuspension. The developed lyophilized nanosuspension was found to be stable for a longer duration of time than the conventional marketed formulation with a good shelf life.

This article aims to provide an interpretation and perspective on current concepts and recent literature regarding the evidence for individualizing intravitreal therapy (IVT), particularly considering iatrogenic and patient factors in the management of neovascular age-related macular degeneration (AMD). As ocular parameters that govern IVT pharmacokinetics do vary between individuals with AMD, developing a personalized strategy could improve safety and efcacy. This has to be derived from clinical measurements and data from laboratory animals; however, it is recognized that the animal models used in the development of intraocular formulations differ in their vitreous geometry from humans. These factors may be of relevance to the design of ophthalmic formulations and optimizing treatment outcomes in AMD. Further studies are needed to drive improvements in clinical practice which are aimed at maximizing the efcacy prole in IVT for AMD by a more rigorous evaluation of patient and surgeon-related variables.

Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review ar...

Ciprofloxacin (CIP) is an antibacterial agent prescribed for the treatment of ocular infections. The objective of the present project is to investigate the effect of surface PEG functionalization of the Nano structured lipid carriers (NLCs) on formulation stability, ocular penetration and distribution. CIP NLCs were tested with different molecular weight (poly ethylene glycol) PEGs ranging from (2 K to 20 K) grafted onto the phospho-lipid and with different chain lengths (14–18 carbons) of phospholipids derivatized with PEG–2K. Drug load in the formulations was maintained at 0.3%w/v. Formulations prepared were evaluated with respect to in vitro release, transcorneal permeation, autoclavability, morphological characteristics and in vivo ocular tissue distribution. Scanning Transmission electron microscopy (STEM) studies revealed that the PEG-CIP-NLCs were spherical in shape. Transcorneal penetration of CIP was optimum with PEG molecular weight in between 2 K–10 K. Carbon chain length of the phospholipid, however, did not affect transcorneal penetration of CIP. In vivo ocular tissue CIP concentrations attained from the various formulations was consistent with the in vitro data obtained. The results suggest that surface functionalization of PEGs, within a specified range of molecular weight and surface packing density, significantly enhance trans-ocular penetration and impart sterilization stabilization characteristics into the formulations.

Dorzolamide ophthalmic drop is one of the most common glaucoma medications but it has a short residence time in the eye. The aim of this study is to develop ocular dorzolamide HCl nanoliposomes (DRZ – nanoliposomes) and to evaluate their potential use for the treatment of ocular hypertension. Nanoliposomes were prepared using Reverse-phase evaporation vesicle (REV) and thin layer hydration (TLH) method with 7:3 and 7:4 molar ratios of phosphatidy lcholine:cholesterol. The physicochemical properties of the formulations were investigated. Formulations with 7:4 lipid ratios were evaluated in terms of drug release, physical stability and ex-vivo permeation through the excised albino rabbit cornea. The rabbits in groups of 6 were treated with selected DRZ – nanoliposomes or dorzolamide solution or marketed dorzolamid preparation (Biosopt®) and intraocular pressure (IOP) was monitored. Formulations with 7:4 molar ratio entrapped greater amount of drug compared to those with 7:3 lipid components ratio. DRZ – nanoliposomes with 7:4 lipid ratio showed more transcorneal permeation than Dorzolamide solution (p<0.05); and the formulation prepared by TLH method exhibited higher permeability than that prepared by REV method (p<0.05). The selected DRZ – nanoliposomes showed greater IOP lowering activity and a more prolonged effect compared to dorzolamide solution and Biosopt®. DRZ – nanoliposomes prepared by TLH method with 7:4 ratios showed promising results as a candidate for the treatment of ocular hypertension.

Our aim was to entrap Amphotericin-B, within the nanoparticles so that it could penetrate the cornea effectively. Solvent displacement method was used to prepare the nanoparticles. Confocal laser scanning microscopy was used to check the corneal penetration of the nanoparticle into isolated goat eyes after contact time of 1 hr and 24 hrs with the formulations. Prepared nanoparticles had particle size range from 112 to 350 nm with a zeta potential of 19 to 34 mV. This positive zeta helps the nanoparticle to adhere with corneal mucosa and release the drug. Almost 60-70% of the drug was released from every formulation in 6 to 7 hrs. The nanoparticles were able to entrap upto 75% of the drug successfully. Ex-vivo study reveals that 50% of the topically applied drug penetrated the cornea within 24 hrs whereas the plain drug solution had negligible penetration capacity.

In situ gel-forming systems have drawn much attention of current researchers to overcome the poor bioavailability from the conventional eye drops. The present work described formulation and pharmacoscintigraphic evaluation of timolol-maleate-loaded chitosan/hydroxy propyl methyl cellulose (HPMC)-based polymer matrix for enhanced ocular retention. Chitosan and HPMC ratio was optimized and formulation was characterized for various in vitro parameters. The ocular retention was studied on New Zealand rabbits by gamma scintigraphy, which is a very simple and noninvasive technique. For scintigraphy study, the drug timolol maleate was radiolabeled 99m Tc by direct labeling method using SnCl 2 ·2H 2 O as reducing agent. The labeling procedure was optimized to get maximum labeling efficiency (>98%). In vitro stability of the radiolabeled drug ( 99m Tc-timolol maleate complex) was checked and it was found to be stable for up to 24 h. Plain drug eliminates rapidly as significant activity was recorded in kidney and bladder after 2 h of ocular administration. It was evident from the scintigraphic images and the time-activity curve plotted from the data that the plain drug solution cleared very rapidly from the corneal region and reached into systemic circulation via nasolachrymal drainage system, as significant activity was recorded in kidney and bladder after 2 h of ocular administration. Developed formulation cleared at a slow rate and remained at corneal surface for longer time duration. No radioactivity was observed in systemic circulation after 2 h. Ocular irritation of the developed formulation was also checked by hen's egg chorioallantoic membrane test and formulation was found to be practically nonirritant. The study signified the potential of gamma scintigraphy in evaluation of novel drug delivery systems in a noninvasive manner.

The aim of the present study was to investigate the antioxidant activity of methanolic extract of Michelia champaca flowers. Antioxidant activity was evaluated by using in-vitro assay models like Total antioxidant capacity, Nitric oxide radical scavenging assay, Reducing Power Assay and Hydrogen Peroxide Scavenging Activity. All the antioxidant activities were compared with standard antioxidant such as ascorbic acid. Methanolic extract of the plant showed effective free radical scavenging activity at 300µg concentration. The IC50 values of the ethanolic extract of Michelia champaca flowers were found to be 260 µg in total antioxidant activity, 150 µg in nitric oxide radical assay, 240 µg in reducing power assay and 280 µg in hydrogen peroxide assay. The results obtained in this study showed that the flowers of Michelia champaca have antioxidant properties which provide a basis for the traditional use of the plant.

The processing of an image, which begins in the retina and continues on the cortex, is provided by two distinct, parallel cellular pathways: the parvocellular (P-) or sustained system, and the magnocellular (M-) or transient system. The P-system is made of small ganglion cells and arranged in receptive fields of small size. In turn, the M-system, is made of larger ganglion cells making up wider receptive fields. Like their anatomical features, also the information carried by the M-and P-cells is different and basically complementary, at least at the subcortical level. A common opinion in the last decades supports the idea that a model based on this parallel M/P complementary processing of the image may account for the various aspects of visual perception. Yet, tracing separately M-and P-information beyond the striate cortex turns difficult due to the diffuse anatomical crossroads, functional intermixing, and to the overlapping of the psychophysical response. The present paper aims at making the point on this issue, pinpointing the already reported caveat for an attractive, albeit probably too simplified (and therefore potentially misleading) schematization.

This work evaluated under accelerated conditions the stability of the
biodegradable gentamicin-glyceryl monooleate water based-gel used
in the treatment of chronic osteomyelitis. Three batches of 600.0 g of
gentamicin -glyceryl monooleate -water based-gel (5/80/15% w/w)
were manufactured. The samples were stored in a climatic test
chamber for stability evaluation according to the standards published
by the International Conference on Harmonisation and the World
Health Oganization (25 ± 2°C / 60 ± 5%RH) for 6 months. Samples
were evaluated at pre-determinate times 0, 3 and 6 months with
regard to their physicochemical properties and In Vitro drug release
characteristics. Gentamicin sulfate present in the freshly prepared
gels was the same after three and six months of storage at 25°C / 60%
RH. However the relative amount of gentamicin sulfate in the freshly
prepared gel that was about 110% decreased by about 11% after six
months of storage. The release profiles of the gels remained similar
despite a partial hydrolysis of glyceryl monooleate and an increase in
the residual amount of water and in the viscosity.

Poor ocular bioavailability of drugs (b1%) from conventional eye drops (ie, solution, suspension, and ointments) is mainly due to the physiologic barriers of the eye. In general, ocular efficacy is closely related to ocular drug bioavailability, which may be enhanced by increasing corneal drug penetration and prolonging precorneal drug residence time. In our current work, we develop and evaluate a new colloidal system, that is, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles for sparfloxacin ophthalmic delivery, to improve precorneal residence time and ocular penetration. Nanoparticles were prepared by nanoprecipitation technique and characterized for various properties such as particle size, zeta potential, in vitro drug release, statistical model fitting, stability, and so forth. Microbiological assay was carried out against Pseudomonas aeruginosa using the cup-plate method. Precorneal residence time was studied in albino rabbits by gamma scintigraphy after radiolabeling of sparfloxacin by Tc-99m. Ocular tolerance of the developed nanosuspension was also studied by the Hen Egg Test-Chorioallantoic Membrane (HET-CAM) method. The developed nanosuspension showed a mean particle size in the range of 180 to 190 nm, suitable for ophthalmic application with zeta potential of -22 mV. In vitro release from the developed nanosuspension showed an extended release profile of sparfloxacin according to the Peppas model. Acquired gamma camera images showed good retention over the entire precorneal area for the developed nanosuspension compared with that of a marketed formulation. The marketed drug formulation cleared very rapidly from the corneal region and reached the systemic circulation through the nasolacrimal drainage system, as significant radioactivity was recorded in kidney and bladder after 6 hours of ocular administration, whereas the developed nanosuspension cleared at a very slow rate (P b .05) and remained at the corneal surface for longer duration, as no radioactivity was observed in the systemic circulation. HET-CAM assay with 0 score in 8 hours indicates the nonirritant property of the developed nanosuspension. The developed lyophilized nanosuspension was found to be stable for a longer duration of time than the conventional marketed formulation with a good shelf life.

Proper availability of drug on to corneal surface is a challenging task. However, due to ocular physiological barriers, conventional eye drops display poor ocular bioavailability of drugs ( 1%). To improve precorneal residence time and ocular penetration, earlier our group developed and evaluated in situ gel and nanoparticles for ocular delivery. In interest to evaluate the combined effect of in situ gel and nanoparticles on ocular retention, we combined them. We are the first to term this combination as "nanoparticle laden in situ gel", that is, poly lactic co glycolic acid nanoparticle incorporated in chitosan in situ gel for sparfloxacin ophthalmic delivery. The formulation was tested for various physicochemical properties. It showed gelation pH near pH 7.2. The observation of acquired gamma camera images showed good retention over the entire precorneal area for sparfloxacin nanoparticle laden in situ gel (SNG) as compared to marketed formulation. SNG formulation cleared at a very slow rate and remained at corneal surface for longer duration as no radioactivity was observed in systemic circulation. The developed formulation was found to be better in combination and can go up to the clinical evaluation and application.

The human eye is a specialized organ with a complex anatomy and physiology, because it is characterized by different cell types with specific physiological functions. Given the complexity of the eye, ocular tissues are finely organized and orchestrated. In the last few years, many in vitro models have been developed in order to meet the 3Rs principle (Replacement, Reduction and Refinement) for eye toxicity testing. This procedure is highly necessary to ensure that the risks associated with ophthalmic products meet appropriate safety criteria. In vitro preclinical testing is now a well-established practice of significant importance for evaluating the efficacy and safety of cosmetic, pharmaceutical, and nutraceutical products. Along with in vitro testing, also computational procedures, herein described, for evaluating the pharmacological profile of potential ocular drug candidates including their toxicity, are in rapid expansion. In this review, the ocular cell types and functionality are described, providing an overview about the scientific challenge for the development of three-dimensional (3D) in vitro models.

Background: A Dyop (or dynamic optotype) is a spinning visual target which uses the strobic detection of the spinning gaps/segments of the ring to measure visual acuity. Methods: Forty subjects with visual acuity better than 6/12 (20/40) and ages between 20 and 28 years (24.48 ± 2.01 years) were recruited at the University of Benin Optometry Clinic. Snellen and Dyop acuity charts were displayed on a monitor at a distance of 6 meters. The assessment sequence between the two acuity chart formats was alternated for every other patient to reduce potential refractionist bias. Subjective refraction was measured in both eyes, and the duration of testing for each patient and each method was recorded. Results: There was no significant mean Thibos notations difference, M (p = 0.77), J0 (p = 0.27), and J45 (p = 0.57) using the Bland-Altman plot and 95% limits of agreement between the two charts, and there were no differences as to age or gender. There was, however, a disparity in the mean acuity of about 0.25 diopters with the mean Snellen acuity of 1.60 ± 0.21 decimal units and the mean Dyop acuity of 1.17 ± 0.14 decimal units with a linear relationship: y = 0.3121x + 0.6709 (p = 0.00). The refraction with a Dyop acuity chart also typically took half as long (339 ± 122 seconds) as the refraction with a Snellen acuity chart (680 ± 281 seconds), p = 0.00.

The eye is one of the most specialized organs in the body; one of its flawless functions is vigorously controlling the foreign materials' entrance to the eye. On the other hand, this feature made it challenging to deliver drug molecules to the eye chamber for therapeutic purposes. Other obstacles related to pharmaceuticals' low efficacy are short resistance time on the eye surfaces because of tear and nasolacrimal drainage. The advent of novel drug delivery systems (DDSs), like nanoparticles, was a milestone to overcome these problems, provided they were adeptly designed. In other words, all parameters influencing DDSs must be considered to attain the desired efficacy. This review discusses liposomes' essential characteristics as one of the most favored carriers that can affect the ocular drug bioavailability and efficacy. Here, we discussed the physiology of the eye, the mechanics of medicine distribution, and other factors affecting drug delivery. Then, all of the liposome's features, including composition, physicochemical properties, and drug targeting capability, which may alter the local distribution of the medication to the eye, were reviewed. In this review paper, prior investigations' outcomes are discussed to create appropriate liposomal vesicles for efficient ocular drug delivery.

Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review ar...

Conventional ophthalmic dosage forms, although being simple to apply and presenting great patients' compliance, display poorer drug bioavailability and retention time on the eye surface. To cope with these problems, one must formulate novel drug delivery systems, such as nanosystems, for ocular drug delivery. Different formulation methods of nanoparticles have been developed, but some of them, such as the supercritical fluid method, have not reached their full potential in ocular drug delivery. This article aims to present the possibilities of the supercritical fluid method when preparing nanosystems for ocular drug delivery. This method could be used more frequently and efficiently because it is environmentally friendly and produces nanoparticles of the desired physicochemical properties, which is especially important in ocular drug delivery considering its peculiarities. Modifications of the supercritical fluid method can be used when a drug has some specific properties, which is an additional benefit in ocular drug delivery.

Purpose: To evaluate the outcome of immediate management in acute ocular chemical burns. Methods: 29 eyes of 19 patients with acute chemical burns were studied. All patients received immediate first aid. Limbal and conjunctival involvement were graded as per Dua's classification. 86.8% patients with grade 1, 2 and 3 were managed conservatively while amniotic membrane transplantation was performed in 13.7% of patients who had grade 4 or grade 5 involvement. All patients were followed up for a period of 6 months.

Poor ocular bioavailability of drugs (b1%) from conventional eye drops (ie, solution, suspension, and ointments) is mainly due to the physiologic barriers of the eye. In general, ocular efficacy is closely related to ocular drug bioavailability, which may be enhanced by increasing corneal drug penetration and prolonging precorneal drug residence time. In our current work, we develop and evaluate a new colloidal system, that is, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles for sparfloxacin ophthalmic delivery, to improve precorneal residence time and ocular penetration. Nanoparticles were prepared by nanoprecipitation technique and characterized for various properties such as particle size, zeta potential, in vitro drug release, statistical model fitting, stability, and so forth. Microbiological assay was carried out against Pseudomonas aeruginosa using the cup-plate method. Precorneal residence time was studied in albino rabbits by gamma scintigraphy after radiolabeling of sparfloxacin by Tc-99m. Ocular tolerance of the developed nanosuspension was also studied by the Hen Egg Test-Chorioallantoic Membrane (HET-CAM) method. The developed nanosuspension showed a mean particle size in the range of 180 to 190 nm, suitable for ophthalmic application with zeta potential of -22 mV. In vitro release from the developed nanosuspension showed an extended release profile of sparfloxacin according to the Peppas model. Acquired gamma camera images showed good retention over the entire precorneal area for the developed nanosuspension compared with that of a marketed formulation. The marketed drug formulation cleared very rapidly from the corneal region and reached the systemic circulation through the nasolacrimal drainage system, as significant radioactivity was recorded in kidney and bladder after 6 hours of ocular administration, whereas the developed nanosuspension cleared at a very slow rate (P b .05) and remained at the corneal surface for longer duration, as no radioactivity was observed in the systemic circulation. HET-CAM assay with 0 score in 8 hours indicates the nonirritant property of the developed nanosuspension. The developed lyophilized nanosuspension was found to be stable for a longer duration of time than the conventional marketed formulation with a good shelf life.

Dorzolamide ophthalmic drop is one of the most common glaucoma medications but it has a short residence time in the eye. The aim of this study is to develop ocular dorzolamide HCl nanoliposomes (DRZ - nanoliposomes) and to evaluate their potential use for the treatment of ocular hypertension. Nanoliposomes were prepared using Reverse-phase evaporation vesicle (REV) and thin layer hydration (TLH) method with 7:3 and 7:4 molar ratios of phosphatidylcholine:cholesterol. The physicochemical properties of the formulations were investigated. Formulations with 7:4 lipid ratios were evaluated in terms of drug release, physical stability and ex-vivo permeation through the excised albino rabbit cornea. The rabbits in groups of 6 were treated with selected DRZ - nanoliposomes or dorzolamide solution or marketed dorzolamid preparation (Biosopt®) and intraocular pressure (IOP) was monitored. Formulations with 7:4 molar ratio entrapped greater amount of drug compared to those with 7:3 lipid compo...

Purpose: To evaluate the outcome of immediate management in acute ocular chemical burns. Methods: 29 eyes of 19 patients with acute chemical burns were studied. All patients received immediate first aid. Limbal and conjunctival involvement were graded as per Dua's classification. 86.8% patients with grade 1, 2 and 3 were managed conservatively while amniotic membrane transplantation was performed in 13.7% of patients who had grade 4 or grade 5 involvement. All patients were followed up for a period of 6 months. Results: 73.6% patients presented with alkali burns while 26.3% patients presented with acid burns. 3.4% eyes had grade I involvement, 55.1% eyes had grade II, 27.5% eyes had grade III, 3.4% eyes had grade IV and 3.4% had grade V involvement. Of 29 eyes, 86% showed epithelialization by 8 weeks, and rest 13.7% showed complete epithelialization by 4 months. On long term follow-up, complications were seen in 13.6% eyes. Symblepharon occurred in 6.8% eyes and rest 6.8% eyes developed corneal vascularization due to secondary limbal stem cell deficiency. None of the eyes showed worsening signs of corneal thinning and perforation. Conclusions: Immediate intervention in acute ocular burns, in the form of medical or surgical, prevents further ocular surface damage, promotes wound healing, and hinders visually debilitating cicatricial sequelae. In our experience, surgical intervention in patients with Grade 4 involvement and above leads to early rehabilitation and gain of visual function.

In situ gel-forming systems have drawn much attention of current researchers to overcome the poor bioavailability from the conventional eye drops. The present work described formulation and pharmacoscintigraphic evaluation of timolol-maleate-loaded chitosan/hydroxy propyl methyl cellulose (HPMC)-based polymer matrix for enhanced ocular retention. Chitosan and HPMC ratio was optimized and formulation was characterized for various in vitro parameters. The ocular retention was studied on New Zealand rabbits by gamma scintigraphy, which is a very simple and noninvasive technique. For scintigraphy study, the drug timolol maleate was radiolabeled 99mTc by direct labeling method using SnCl2·2H2O as reducing agent. The labeling procedure was optimized to get maximum labeling efficiency (>98%). In vitro stability of the radiolabeled drug (99mTc-timolol maleate complex) was checked and it was found to be stable for up to 24 h. Plain drug eliminates rapidly as significant activity was recorded in kidney and bladder after 2 h of ocular administration. It was evident from the scintigraphic images and the time–activity curve plotted from the data that the plain drug solution cleared very rapidly from the corneal region and reached into systemic circulation via nasolachrymal drainage system, as significant activity was recorded in kidney and bladder after 2 h of ocular administration. Developed formulation cleared at a slow rate and remained at corneal surface for longer time duration. No radioactivity was observed in systemic circulation after 2 h. Ocular irritation of the developed formulation was also checked by hen’s egg chorioallantoic membrane test and formulation was found to be practically nonirritant. The study signified the potential of gamma scintigraphy in evaluation of novel drug delivery systems in a noninvasive manner.