Solid Lipid Nanoparticles

The objective of this research is to formulate and evaluate Solid Lipid Nanoparticles containing Acyclovir by various phospholipids and surfactants using hot homogenization technique. Totally nine batches of SLN was formulated by hot homogenization technique and evaluates for PS,ZP,PI,Drug content, Entrapment efficiency, Invitro drug release studies and Invitro release kinetics studies. From the data's, it was concluded that hot homogenization technique method followed by ultrasonication was an optimized technique for the preparation of SLN nanoparticles containing Acyclovir, which lead to better results like high entrapment efficiency, high drug content and SLS was a better choice of surfactant to reduce the particle size and leads to uniform distribution of SLN in its phase. So, SLN will be an alternative drug delivery system for acyclovir to enhance the bioavailability and therapeutic response of drug.

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.

Background: Topical drug administration offers an attractive route with minimal invasiveness. It also avoids limitations of intravenous administration such as the first pass metabolism and presystemic elimination within the gastrointestinal tract. Furthermore, topical drug administration is safe, have few side effects, is easy to apply, and offers a fast onset of action. However, the development of effective topical formulations still represents a challenge for the desired effect to be reached, locally or systemically. Solid lipid nanoparticles and nanos-tructured lipid carriers are particular candidates to overcome the problem of topical drug administration. The nanometric particle size of lipid nanoparticles favors the physical adhesion to the skin or mucosal, what can also be attained with the formation of hybrid (nanoparticles/polymer) systems. Methods: In this review, we discuss the major challenges for lipid nanoparticles formulations for topical application to oral mucosa, skin, and eye, highlighting the strategies to improve the performance of lipid nanoparticles for topical applications. Next, we critically analyzed the in vitro and in vivo approaches used to evaluate lipid nanoparticles performance and toxicity. Conclusion: We addressed some major drawbacks related to lipid nanoparticle topical formulations and concluded the key points that have to be overcome to help them to reach the market in topical formulations to oral mucosa, skin, and eye.

Lipid nanoparticles based on solid matrix have emerged as potential drug carriers to improve gastrointestinal (GI) absorption and oral bioavailability of several drugs, especially lipophilic compounds. These formulations may also be used for sustained drug release. Solid lipid nanoparticle (SLN) and the newer generation lipid nanoparticle, nanostructured lipid carrier (NLC), have been studied for their capability as oral drug carriers. Biodegradable, biocompatible, and physiological lipids are generally used to prepare these nanoparticles. Hence, toxicity problems related with the polymeric nanoparticles can be minimized. Furthermore, stability of the formulations might increase than other liquid nano-carriers due to the solid matrix of these lipid nanoparticles. These nanoparticles can be produced by different formulation techniques. Scaling up of the production process from lab scale to industrial scale can be easily achieved. Reasonably high drug encapsulation efficiency of the n...

The main aim of pharmaceutical technology research is the design of successful formulations for effective therapy, taking into account several issues including therapeutic requirements and patient compliance. In this regard, several achievements have been reported with colloidal carriers, in particular with lipid nanoparticles, due to their unique physicochemical properties. For several years these carriers have been showing potential success for several administration routes, namely oral, dermal, parenteral, and, more recently, for pulmonary and brain targeting. The present chapter provides a review of the use of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) to modify the release profile and the pharmacokinetic parameters of active pharmaceutical ingredients (APIs) incorporated in these lipid matrices, aiming to modify the API bioavailability, either upwards or downwards depending on the therapeutic requirement. Definitions of the morphological characteristics, surface properties, and polymorphic structures will also be given, emphasizing their influence on the incorporation parameters of the API, such as yield of production, loading capacity, and encapsulation efficiency.

Several scientific hurdles still have to be overcome before gene therapy becomes a reality. One of them is the development of safe and efficient gene delivery system. Here, we have employed factorial design to optimize the production of solid lipid nanoparticles (SLN) for gene delivery. A 2×3 full-factorial experimental design was used for the optimization of SLNs formulations. The variables were defined by the components of the formulation: concentration of stearic acid, DOTAP, and Pluronic F68 at two levels (−1, 1) and 3 central points (0). Different SNL formulations were prepared by varying the amount of components and several properties were tested, including their capacity to accommodate DNA and protection against DNase degradation, colloidal stability, in vitro cytotoxicity, and transfection efficiency in prostate cancer cells. Finally, response Surface Methodology was used to select the most effective formulation for gene delivery to prostate cancer cells in vitro. In conclusion, this study revealed that stearic acid and Pluronic F68 were determinant to SLN size and stability, respectively, while small amounts of DOTAP are essential for a successful transfection.

Solid lipid nanoparticles (SLNs) have attracted increasing attention during recent years. Due to their unique size dependent properties, lipid nanoparticles offer possibilities to develop new therapeutics. The ability to incorporate drugs into nanoparticles offers a new prototype in drug delivery thus realizing the dual goal of both controlled release and site-specific drug delivery. Drug delivery to the skin is widely used for local and systemic delivery and has potential to be improved by application of nanoparticulate formulations. If investigated appropriately, solid lipid nanoparticles may open new opportunities in therapy of complex diseases which is difficult to treat.

Solid lipid nanoparticles (SLNs) have been proposed in the 1990s as appropriate drug delivery systems, and ever since they have been applied in a wide variety of cosmetic and pharmaceutical applications. In addition, SLNs are considered suitable alternatives as carriers in gene delivery. Although important advances have been made in this particular field, fundamental knowledge of the underlying mechanisms of SLN-mediated gene delivery is conspicuously lacking, an imperative requirement in efforts aimed at further improving their efficiency. Here, we address recent advances in the use of SLNs as platform for delivery of nucleic acids as therapeutic agents. In addition, we will discuss available technology for conveniently producing SLNs. In particular, we will focus on underlying molecular mechanisms by which SLNs and nucleic acids assemble into complexes and how the nucleic acid cargo may be released intracellularly. In discussing underlying mechanisms, we will, when appropriate, refer to analogous studies carried out with systems based on cationic lipids and polymers, that have proven useful in the assessment of structure–function relationships. Finally, we will give suggestions for improving SLN-based gene delivery systems, by pointing to alternative methods for SLNplex assembly, focusing on the realization of a sustained nucleic acid release.

Nanotechnology is rapidly expanding research area, encompassing
the development of man-made materials in nanometer size range.
Nanoscale drug delivery system using various nanomaterials is
emerging technology for the rational delivery of many
chemotherapeutic agents. Nanoparticles attracted the scientists
across many disciplines to engineer many desired properties that
might otherwise be incompatible on a single device. Formulation
scientists are facing the challenges such as poor solubility and
bioavailability of the newly invented drugs. One of the approaches
to face the above challenge is to develop the particulate carrier
system. Solid lipid nanoparticle or liposphere or nanosphere
system is the most feasible particulate carrier system which is an
alternative to nanoemulsions, liposomes and polymeric
nanoparticles. This system offers added advantages in comparison
to other related particulate drug delivery systems. The present
review emphasizes on various basic and applied aspects of solid
lipid nanoparticles in novel drug delivery system especially
techniques involved in their production, characterization and
various applications. It also focuses on the drug loading capacity,
drug incorporation and factors affecting drug release from this
colloidal system

The aim of this study was to formulate a new delivery system for ecological pesticides by the incorporation of Artemisia arborescens L essential oil into solid lipid nanoparticles (SLN). Two different SLN formulations were prepared following the high-pressure homogenization technique using Compritol 888 ATO as lipid and Poloxamer 188 or Miranol Ultra C32 as surfactants. The SLN formulation particle size was determined using Photon correlation spectroscopy (PCS) and laser diffraction analysis (LD). The change of particle charge was studied by zeta potential (ZP) measurements, while the melting and recrystallization behavior was studied using differential scanning calorimetry (DSC). In vitro release studies of the essential oil were performed at 35°C. Data showed a high physical stability for both formulations at various storage temperatures during 2 months of investigation. In particular, average diameter of Artemisia arborescens L essential oil-loaded SLN did not vary during storage and increased slightly after spraying the SLN dispersions. In vitro release experiments showed that SLN were able to reduce the rapid evaporation of essential oil if compared with the reference emulsions. Therefore, obtained results showed that the studied SLN formulations are suitable carriers in agriculture.

Amphotericin B (BCS-Class IV) is the major treatment available against the fatal infection of Visceral
leishmaniasis. Conventional chemotherapy of AMB is challenging because of its severe and potentially
lethal side-effects i.e., nephrotoxicity and hepatotoxicity. Therefore, there is an urgent need
of designing novel, leishmanicidal drug carriers for safe and effective management of VL. Colloidal
carriers like liposomes, niosomes and emulsomes offer better therapeutic efficacy over the conventional
treatment with reduced side effects and toxicity but suffer with the stability problem. Lipid
nanoparticles are stable, biodegradable, biocompatible carrier offering excellent therapeutic efficacy.
Here, an effort has been made to prepare novel nanostructured lipid carriers of AMB to increase
therapeutic efficacy and reduced toxicity with the use of microfluidizer. Different formulations were
prepared and optimized by varying pressure and number of cycles. Formulations were selected
for further studies on the basis of particle size and particle size distribution. The drug entrapment
efficiency was achieved up to 90.1% with particle size 148±2
7 nm of the formulation and zeta
potential of −30±1
8 mv. The optimized formulation was found stable for more than 6 months in
terms of particle size and size distribution. The characterization of the formulation was done using
Scanning Electron Microscopy and Transmission Electron Microscopy. The in vitro release profile
of the AMB loaded NLCs showed 65% drug release within 24 hours. The optimized formulations
were found within the permissible range of haemolysis and cytotoxicity. The findings suggested that
it would be preferable to deliver AMB through nanostructured lipid carriers.
Keywords: Visceral Leishmaniasis, Amphotericin B, Microfluidizer, Lipid Nanoparticles

A B S T R A C T Myricetin-a natural flavonoid-has attracted a great interest due to its antioxidant and free-radical scavenging potential. However, its physicochemical instability critically impairs its dosage form design, evaluation and administration. In an attempt to protect from degradation, MYR was encapsulated into Gelucire-based solid lipid nanoparticles (SLNs). The impact of medium pH, processing temperature and different additives on the drug degradation either in free or nanoencapsulated form was assessed. MYR stability was further monitored in essential biorelevant fluids. Investigations have led to the recommendation that the presence of fat-soluble antioxidant is necessary during SLN preparation to protect the drug at high temperature. Meanwhile, physiological buffers as well as simulated fluids should be supplemented with stabilizers as tween 80 and Poloxamer 407, in addition to water-soluble antioxidant such as sodium sulfite. Interestingly, mucin-containing fluids are suggested to provide better protection to MYR, in contrast, cell culture media do not guarantee MYR stability. The degradation kinetics changed from 1st to 2nd order mechanism after MYR nanoencapsulation. In presence of the aforementioned additives, MYR-SLNs significantly reduced the drug degradation rate constant up to 300-folds and prolonged the half-life time up to 4500-folds compared to free MYR in physiological buffers (One-way ANOVA, p < 0.05). As a proof of concept, in vitro release experiment in presence of phosphate buffer (pH 7.4) supplemented with these additives ensured sustained release of MYR over > 8 h with no signs of degradation. The study emphasizes virtuous guidance regarding appropriate nanoencapsulation conditions and evaluation attributes ensuing MYR physicochemical stability.

Delivering chemotherapeutics by nanoparticles into tumor is impeded majorly by two factors: nonspecific targeting and inefficient penetration. Targeted delivery of anti-cancer agents solely to tumor cells introduces a smart strategy because it enhances the therapeutic index compared with untargeted drugs. The present study was performed to investigate the efficiency of adenosine (ADN) to target solid lipid nanoparticles (SLN) to over expressing adenosine receptor cell lines such as human breast cancer and prostate cancer (MCF-7 and DU-145 cells), respectively. SLN were prepared by emulsification and solvent evaporation process using docetaxel (DTX) as drug and were characterized by various techniques like dynamic light scattering, differential scanning calorimeter and transmission electron microscopy. DTX loaded SLNs were surface modified with ADN, an adenosine receptors ligand using carbodiimide coupling. Conjugation was confirmed using infrared spectroscopy and quantified using phenol–sulfuric acid method. Conjugated SLN were shown to have sustained drug release as compared to unconjugated nanoparticles and drug suspension. Compared with free DTX and unconjugated SLN, ADN conjugated SLN showed significantly higher cytotoxicity of loaded DTX, as evidenced by in vitro cell experiments. The IC50 was 0.41mg/ml for native DTX, 0.30mg/ml for unconjugated SLN formulation, and 0.09mg/ml for ADN conjugated SLN formulation in MCF-7 cell lines. Whereas, in DU-145, there was 2 fold change in IC50 of ADN–SLN as compared to DTX. IC50 was found to be 0.44mg/ml for free DTX, 0.39mg/ml for unconjugated SLN and 0.22mg/ml for ADN–SLN. Annexin assay and cell cycle analysis assay further substantiated the cell cytotoxicity. Fluorescent cell uptake and competitive ligand-receptor binding assay corroborated the receptor mediated endocytosis pathway indicated role of adenosine receptors in internalization of conjugated particles. Pharmacokinetic studies of lipidic formulations depicted significant improvement in pharmacokinetic parameters than marketed formulation. ADN conjugated SLN proved to be an efficient drug delivery vehicle. Hence, ADN can be used as a potential ligand to target breast and prostate cancer.Delivering chemotherapeutics by nanoparticles into tumor is impeded majorly by two factors: nonspecific targeting and inefficient penetration. Targeted delivery of anti-cancer agents solely to tumor cells introduces a smart strategy because it enhances the therapeutic index compared with untargeted drugs. The present study was performed to investigate the efficiency of adenosine (ADN) to target solid lipid nanoparticles (SLN) to over expressing adenosine receptor cell lines such as human breast cancer and prostate cancer (MCF-7 and DU-145 cells), respectively. SLN were prepared by emulsification and solvent evaporation process using docetaxel (DTX) as drug and were characterized by various techniques like dynamic light scattering, differential scanning calorimeter and transmission electron microscopy. DTX loaded SLNs were surface modified with ADN, an adenosine receptors ligand using carbodiimide coupling. Conjugation was confirmed using infrared spectroscopy and quantified using phenol–sulfuric acid method. Conjugated SLN were shown to have sustained drug release as compared to unconjugated nanoparticles and drug suspension. Compared with free DTX and unconjugated SLN, ADN conjugated SLN showed significantly higher cytotoxicity of loaded DTX, as evidenced by in vitro cell experiments. The IC50 was 0.41mg/ml for native DTX, 0.30mg/ml for unconjugated SLN formulation, and 0.09mg/ml for ADN conjugated SLN formulation in MCF-7 cell lines. Whereas, in DU-145, there was 2 fold change in IC50 of ADN–SLN as compared to DTX. IC50 was found to be 0.44mg/ml for free DTX, 0.39mg/ml for unconjugated SLN and 0.22mg/ml for ADN–SLN. Annexin assay and cell cycle analysis assay further substantiated the cell cytotoxicity. Fluorescent cell uptake and competitive ligand-receptor binding assay corroborated the receptor mediated endocytosis pathway indicated role of adenosine receptors in internalization of conjugated particles. Pharmacokinetic studies of lipidic formulations depicted significant improvement in pharmacokinetic parameters than marketed formulation. ADN conjugated SLN proved to be an efficient drug delivery vehicle. Hence, ADN can be used as a potential ligand to target breast and prostate cancer.

The present study has been focused on determination and evaluation of three different preparation techniques, i.e., solvent-diffusion, hot homogenization-ultrasonification and microemulsification, applied in fabrication of biocompatible phosphatidylcholine solid lipid nanoparticles ((PC)-SLNs), containing Polawax National Formulary (NF) in the internal lipid phase. The fabricated lipid nanoparticles were loaded with the newly synthesized flavonoid cocrystals, i.e., baicalein–nicotinamide (1:1) (BaiNam), myricetin–piracetam (1:1) (MyrPac) and myricetin–caffeine (1:1) (MyrCaf) cocrystals in relation to the starting flavonoids, differing in solubility and physical state. The assessment of all studied drugs entrapment and availability in aqueous SLN dispersions has been carried out; the size along with size distribution of lipid nanoparticles loaded with the studied flavonoids cocrystals and flavonoids was determined by the DLS technique, while the structural changes—by FT-IR spectroscopy and X-ray powder diffraction (XRPD) of the lipid nanomatrices. XRPD and FT-IR analyses confirmed that parent flavonoids as well as their cocrystals are present in the nanoparticles fabricated with solvent-diffusion method as physical mixtures with the lipid and their crystalline structures at least partially conserved. Summarizing, we designed and fabricated the biocompatible SLN-type nanocarriers of enhanced physical stability and availability for the flavonoids delivery—a vast group of naturally occurring polyphenolic compounds, considered as active pharmaceutical ingredients.

The present investigation was enthused by the possibility to develop solid lipid nanoparticles (SLNs) of hydrophilic drug acyclovir (ACV) and evaluate their potential as the carrier for dermal delivery. ACV-loaded SLNs (ACV-SLNs) were prepared by the optimized double emulsion process using Compritol 888 ATO as solid lipid. The prepared SLNs were smooth and spherical in shape with average diameter, polydispersity index, and entrapment efficiency of 262 ± 13 nm, 0.280 ± 0.01, and 40.08 ± 4.39% at 10% (w/w) theoretical drug loading with respect to Compritol 888 ATO content. Differential scanning calorimetry and powder X-ray diffraction pattern revealed that ACV was present in the amorphous state inside the SLNs. In vitro skin permeation studies on human cadaver and Sprague–Dawley rat skin revealed 17.65 and 15.17 times higher accumulation of ACV-SLNs in the dermal tissues in comparison to commercially available ACV cream after 24 h. Mechanism of topical permeation and dermal distribution was studied qualitatively using confocal laser scanning microscopy. While free dye (calcein) failed to penetrate skin barrier, the same encapsulated in SLNs penetrated deeply into the dermal tissue suggesting that pilosebaceous route was followed by SLNs for skin penetration. Histological examination and transdermal epidermal water loss measurement suggested that no major morphological changes occurred on rat skin surface due to the application of SLNs. Overall, it was concluded that ACV-loaded SLNs might be beneficial in improving dermal delivery of antiviral agent(s) for the treatment of topical herpes simplex infection.

Bioactive products from snail slime of " Helix " specie have potential applications in preventing and/or treating several human diseases and in cancer diagnosis. However, the poor pharmacokinetics characteristics of these natural compounds limit their use. Nanotechnology offers promising solutions for the enhanced formulation of these molecules through the synthesis of nanosized drug delivery systems. These vectors are characterized by facilitated transport across the biological barriers, enhanced bioavailability, targeted delivery and the capacity to protect sensitive compounds from biological and environmental degradation. Overall, this review focus on the description of bioactive natural substances derived from snails belonging to the genus helix and their successfully combinations with nanosized vectors.