Leucinostatin A (Leu-A) is a nonapeptide exerting a remarkable activity especially against Candid... more Leucinostatin A (Leu-A) is a nonapeptide exerting a remarkable activity especially against Candida albicans and Cryptococcus neoformans; nevertheless, its employment is limited due its toxicity. Therefore, we recently developed liposomal formulations, as suitable delivery systems, in order to increase its therapeutic index. However, liposomes present disadvantages related to their long-term instability. For this reason poly(lactic-co-glycolic) nanospheres (NS) were chosen as alternative colloidal carriers for Leu-A delivery. NS were formulated by spontaneous emulsification solvent diffusion method. This study investigates the effects of different parameters on drug encapsulation efficiency and particle size as well. The best preparation obtained was also characterized for its in vitro release, in vivo acute toxicity (LD 50), and effectiveness against C. albicans in mice. In vitro release was performed over 100 h and resulted sufficiently sustained with more than 93% of the peptide released. Acute toxicity showed that the LD 50 was increased more than 18-fold and the study on systemic candidiasis models revealed high effectiveness of the NS in reducing either the growth of fungal colonies in infected mice liver or in the mortality index. In conclusion, we can propose that Leu-A loaded NS could represent a new promising therapeutic system against Candida infection.
International journal of pharmaceutics, Jan 15, 2013
The aim of the work was to assess the long-term stability and the safety of lipid nanoparticles i... more The aim of the work was to assess the long-term stability and the safety of lipid nanoparticles intended for brain drug delivery. Lipid nanoparticles, prepared by high pressure homogenization, were stored at room temperature and 4°C and monitored for their mean hydrodynamic diameter and Gaussian distribution width over time. Cetylpalmitate and polysorbate(®) 80 chemical integrity were investigated by nuclear magnetic resonance on diagnostic signals. Nanoparticle toxicity was assessed in chicken embryos by chorioallantoic membrane assay and in rodents by brain histological evaluation. Data showed nanoparticle stability at 4°C over a period of time of 4 years with only a limited particle size increase while at room temperature destabilization was observed after 9 months. Nuclear magnetic resonance investigation confirmed the absence (<5%) of chemical degradation of the lipid matrix and the surfactant after 4 years of storage at 4°C. Chorioallantoic membrane assay and rat brain hist...
International journal of pharmaceutics, Jan 20, 2013
The purpose of this study was to produce low-releasing spray-dried polymeric microparticles (MP) ... more The purpose of this study was to produce low-releasing spray-dried polymeric microparticles (MP) useful to target alveolar macrophages in tuberculosis (TB) inhalation therapy. Ofloxacin (Ofx) was encapsulated as ofloxacin-palladium (Ofx-Pd) complex into poly DL-lactide (PLA) MP by spray-drying. Ofx-Pd was prepared according to a method previously reported. A D-optimal design was employed to optimize drug content (DC), aerodynamic diameter (d(ae)) and span. d(ae) was calculated coupling tap-density to particle size analysis. The MP were characterized by SEM, UV spectrophotometry, and DSC. In vitro drug release was performed in comparison to Ofx loaded PLA MP. The Ofx-Pd complex formed spontaneously with a 1:1 stoichiometry. Inlet temperature, drug loading and polymer concentration resulted the most influential. Optimal MP had span of 0.9, a round shape, d(ae) of 2.5 μm, and DC of 30% (w/w). DSC and SEM analyses correlated with particle size. The optimized MP formulation showed a very...
A new formulation for topical administration of drugs in the oral cavity has been developed using... more A new formulation for topical administration of drugs in the oral cavity has been developed using several film-forming and mucoadhesive polymers. The films have been evaluated in terms of swelling, mucoadhesion and organoleptic characteristics. The best film, containing polyvinylpyrrolidone (PVP) as film-forming polymer and carboxymethylcellulose sodium salt (NaCMC) as mucoadhesive polymer, was loaded with ibuprofen as a model compound and in vitro and in vivo release studies were performed. Statistical investigation of in vitro release revealed that the diffusion process was the main drug release mechanism and the Higuchi's model provided the best fit. In vivo studies showed the presence of ibuprofen in saliva (range 70 -210 Ag/ml) for 5 h and no irritation was observed. These mucoadhesive formulations offer many advantages in comparison to traditional treatments and can be proposed as a new therapeutic tool against dental and buccal diseases and disturbs. D
Cell encapsulation technology raises hopes in medicine and biotechnology. Encapsulated pancreatic... more Cell encapsulation technology raises hopes in medicine and biotechnology. Encapsulated pancreatic islets is a promising approach for the final solution of Type 1 diabetes. Unfortunately, evidence of long-term encapsulated islet graft survival and functional competence lies behind expectancy. Failure was often ascribed to the lack of biocompatibility generating inflammatory response, or limited immunobarrier competence or hypoxia or finally, low h-cell replication. In order to prevent severe inflammation at early stages after implantation, composite microcapsules were designed. Biodegradable microspheres containing ketoprofen were enveloped into the well established alginate/poly-l-ornithine/alginate capsules. Polyester microspheres were prepared, by solvent evaporation, and characterized for encapsulation efficiency, particle size and in vitro release. Biocompatibility and efficacy to prevent the inflammatory response were studied in vivo. Good encapsulation efficiency and the desired particle size were achieved. In vitro release studies evidenced a high burst effect probably due to a plasticizing effect of both water and ketoprofen. The composite systems showed good biocompatibility and capacity to completely avoid the inflammatory response and the pericapsular cell overgrowth. In conclusion, the inflammatory response in the immediate posttransplant period can be circumvented using multicompartment microcapsules releasing non-steroidal anti inflammatory drugs. D 2005 Published by Elsevier B.V.
Leucinostatin A (Leu-A) is a nonapeptide exerting a remarkable activity especially against Candid... more Leucinostatin A (Leu-A) is a nonapeptide exerting a remarkable activity especially against Candida albicans and Cryptococcus neoformans; nevertheless, its employment is limited due its toxicity. Therefore, we recently developed liposomal formulations, as suitable delivery systems, in order to increase its therapeutic index. However, liposomes present disadvantages related to their long-term instability. For this reason poly(lactic-co-glycolic) nanospheres (NS) were chosen as alternative colloidal carriers for Leu-A delivery. NS were formulated by spontaneous emulsification solvent diffusion method. This study investigates the effects of different parameters on drug encapsulation efficiency and particle size as well. The best preparation obtained was also characterized for its in vitro release, in vivo acute toxicity (LD 50), and effectiveness against C. albicans in mice. In vitro release was performed over 100 h and resulted sufficiently sustained with more than 93% of the peptide released. Acute toxicity showed that the LD 50 was increased more than 18-fold and the study on systemic candidiasis models revealed high effectiveness of the NS in reducing either the growth of fungal colonies in infected mice liver or in the mortality index. In conclusion, we can propose that Leu-A loaded NS could represent a new promising therapeutic system against Candida infection.
International journal of pharmaceutics, Jan 15, 2013
The aim of the work was to assess the long-term stability and the safety of lipid nanoparticles i... more The aim of the work was to assess the long-term stability and the safety of lipid nanoparticles intended for brain drug delivery. Lipid nanoparticles, prepared by high pressure homogenization, were stored at room temperature and 4°C and monitored for their mean hydrodynamic diameter and Gaussian distribution width over time. Cetylpalmitate and polysorbate(®) 80 chemical integrity were investigated by nuclear magnetic resonance on diagnostic signals. Nanoparticle toxicity was assessed in chicken embryos by chorioallantoic membrane assay and in rodents by brain histological evaluation. Data showed nanoparticle stability at 4°C over a period of time of 4 years with only a limited particle size increase while at room temperature destabilization was observed after 9 months. Nuclear magnetic resonance investigation confirmed the absence (<5%) of chemical degradation of the lipid matrix and the surfactant after 4 years of storage at 4°C. Chorioallantoic membrane assay and rat brain hist...
International journal of pharmaceutics, Jan 20, 2013
The purpose of this study was to produce low-releasing spray-dried polymeric microparticles (MP) ... more The purpose of this study was to produce low-releasing spray-dried polymeric microparticles (MP) useful to target alveolar macrophages in tuberculosis (TB) inhalation therapy. Ofloxacin (Ofx) was encapsulated as ofloxacin-palladium (Ofx-Pd) complex into poly DL-lactide (PLA) MP by spray-drying. Ofx-Pd was prepared according to a method previously reported. A D-optimal design was employed to optimize drug content (DC), aerodynamic diameter (d(ae)) and span. d(ae) was calculated coupling tap-density to particle size analysis. The MP were characterized by SEM, UV spectrophotometry, and DSC. In vitro drug release was performed in comparison to Ofx loaded PLA MP. The Ofx-Pd complex formed spontaneously with a 1:1 stoichiometry. Inlet temperature, drug loading and polymer concentration resulted the most influential. Optimal MP had span of 0.9, a round shape, d(ae) of 2.5 μm, and DC of 30% (w/w). DSC and SEM analyses correlated with particle size. The optimized MP formulation showed a very...
A new formulation for topical administration of drugs in the oral cavity has been developed using... more A new formulation for topical administration of drugs in the oral cavity has been developed using several film-forming and mucoadhesive polymers. The films have been evaluated in terms of swelling, mucoadhesion and organoleptic characteristics. The best film, containing polyvinylpyrrolidone (PVP) as film-forming polymer and carboxymethylcellulose sodium salt (NaCMC) as mucoadhesive polymer, was loaded with ibuprofen as a model compound and in vitro and in vivo release studies were performed. Statistical investigation of in vitro release revealed that the diffusion process was the main drug release mechanism and the Higuchi's model provided the best fit. In vivo studies showed the presence of ibuprofen in saliva (range 70 -210 Ag/ml) for 5 h and no irritation was observed. These mucoadhesive formulations offer many advantages in comparison to traditional treatments and can be proposed as a new therapeutic tool against dental and buccal diseases and disturbs. D
Cell encapsulation technology raises hopes in medicine and biotechnology. Encapsulated pancreatic... more Cell encapsulation technology raises hopes in medicine and biotechnology. Encapsulated pancreatic islets is a promising approach for the final solution of Type 1 diabetes. Unfortunately, evidence of long-term encapsulated islet graft survival and functional competence lies behind expectancy. Failure was often ascribed to the lack of biocompatibility generating inflammatory response, or limited immunobarrier competence or hypoxia or finally, low h-cell replication. In order to prevent severe inflammation at early stages after implantation, composite microcapsules were designed. Biodegradable microspheres containing ketoprofen were enveloped into the well established alginate/poly-l-ornithine/alginate capsules. Polyester microspheres were prepared, by solvent evaporation, and characterized for encapsulation efficiency, particle size and in vitro release. Biocompatibility and efficacy to prevent the inflammatory response were studied in vivo. Good encapsulation efficiency and the desired particle size were achieved. In vitro release studies evidenced a high burst effect probably due to a plasticizing effect of both water and ketoprofen. The composite systems showed good biocompatibility and capacity to completely avoid the inflammatory response and the pericapsular cell overgrowth. In conclusion, the inflammatory response in the immediate posttransplant period can be circumvented using multicompartment microcapsules releasing non-steroidal anti inflammatory drugs. D 2005 Published by Elsevier B.V.
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Papers by Maurizio Ricci