The Experts below are selected from a list of 93 Experts worldwide ranked by ideXlab platform
Yogeshvar N. Kalia - One of the best experts on this subject based on the ideXlab platform.
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Transdermal Iontophoretic Delivery of Vapreotide Acetate AcrossPorcine Skin in Vitro
Pharmaceutical Research, 2005Co-Authors: Yannic B. Schuetz, Aarti Naik, Evelyne Vuaridel, Yogeshvar N. KaliaAbstract:Purpose The purpose of this study was to evaluate the feasibility of delivering Vapreotide, a somatostatin analogue, by transdermal iontophoresis. Methods In vitro experiments were conducted using dermatomed porcine ear skin and heat-separated epidermis. In addition to quantifying Vapreotide transport into and across the skin, the effect of peptide delivery on skin permselectivity was also measured. The influence of (1) current density, (2) pre- and post-treatment of the skin, (3) competitive ions, and (4) inclusion of albumin in the receptor on Vapreotide delivery were investigated. Results Epidermis proved to be a better model than dermatomed skin for Vapreotide transport studies. Despite the susceptibility of Vapreotide to enzymatic degradation, a flux of 1.7 μg/cm^2 per hour was achieved after 7 h of constant current iontophoresis (0.15 mA/cm^2). Post-iontophoretic extraction revealed that, depending on the experimental conditions, 80–300 μg of peptide were bound to the skin. Vapreotide was found to interact with the skin and displayed a current-dependent inhibition of electroosmosis. However, neither the pre-treatment strategies to saturate the putative binding sites nor the post-treatment protocols to displace the bound peptide were effective. Conclusion Based on the observed transport rate of Vapreotide across porcine epidermis and its clinical pharmacokinetics, therapeutic concentrations should be achievable using a 15-cm^2 patch.
Bruno Gander - One of the best experts on this subject based on the ideXlab platform.
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importance of single or blended polymer types for controlled in vitro release and plasma levels of a somatostatin analogue entrapped in pla plga microspheres
Journal of Controlled Release, 2004Co-Authors: Maria J Blancoprieto, M A Campanero, Kamel Besseghir, F Heimgatner, Bruno GanderAbstract:The aim of the work was to develop biodegradable microspheres for controlled delivery of the somatostatin analogue Vapreotide and maintenance of sustained plasma levels over 2-4 weeks after a single injection in rats. Vapreotide was microencapsulated into end-group capped and uncapped low molecular weight poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) by spray-drying and coacervation. Microspheres were prepared from single and blended (1:1) polymer types. The microparticles were characterized for peptide loading, in vitro release and pharmocokinetics in rats. Spray-drying and coacervation produced microspheres in the size range of 1-15 and 10-70 microm, respectively, and with encapsulation efficiencies varying between 46% and 87%. In vitro release of Vapreotide followed a regular pattern and lasted more than 4 weeks, time at which 40-80% of the total dose were released. Microspheres made of 14-kDa end-group uncapped PLGA50:50 or 1:1 blends of this polymer with 35 kDa end-group uncapped PLGA50:50 gave the best release profiles and yielded the most sustained plasma levels above a pre-defined 1 ng/ml over approximately 14 days. In vitro/in vivo correlation analyses showed for several microsphere formulations a linear correlation between the mean residence time in vivo and the mean dissolution time (r=0.958) and also between the amount released between 6 h and 14 days and the AUC(6h-14d) (r=0.932). For several other parameters or time periods, no in vitro/in vivo correlation was found. This study demonstrates that controlled release of the Vapreotide is possible in vivo for a duration of a least 2 weeks when administered i.m. to rats. These results constitute a step forward towards a twice-a-month or once-a-month microsphere-formulation for the treatment of acromegaly and neuroendocrine tumors.
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importance of the test medium for the release kinetics of a somatostatin analogue from poly d l lactide co glycolide microspheres
International Journal of Pharmaceutics, 1999Co-Authors: Maria J Blancoprieto, Kamel Besseghir, Piero Orsolini, Frederic Heimgartner, Christine Deuschel, Hans P Merkle, Ho Namtrân, Bruno GanderAbstract:The determination of in vitro release kinetics of peptides from poly(d,l-lactide-co-glycolide) (PLGA) microspheres generally requires optimization of the test conditions for a given formulation. This is particularly important when in vitro/in vivo correlation should be determined. Here, the somatostatin analogue Vapreotide pamoate, an octapeptide, was microencapsulated into PLGA 50:50 by spray-drying. The solubility of this peptide and its in vitro release kinetics from the microspheres were studied in various test media. The solubility of Vapreotide pamoate was approximately 20-40 microg/ml in 67 mM phosphate buffer saline (PBS) at pH 7.4, but increased to approximately 500-1000 microg/ml at a pH of 3.5. At low pH, the solubility increased with the buffer concentration (1-66 mM). Very importantly, proteins (aqueous bovine serum albumin (BSA) solution or human serum) appeared to solubilize the peptide pamoate, resulting in solubilities ranging from 900 to 6100 microg/ml. The release rate was also greatly affected by the medium composition. Typically, in PBS of pH 7.4, only 33+/-1% of the peptide were released within 4 days, whereas 53+/-2 and 61+/-0.9% were released in 1% BSA solution and serum, respectively. The type of medium was found critical for the estimation of the in vivo release. The in vivo release kinetics of Vapreotide pamoate from PLGA microspheres following administration to rats were qualitatively in good agreement with those obtained in vitro using serum as release medium. Finally, sterilization by gamma-irradiation had only a minor effect on the in vivo pharmacokinetics.
Kamel Besseghir - One of the best experts on this subject based on the ideXlab platform.
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importance of single or blended polymer types for controlled in vitro release and plasma levels of a somatostatin analogue entrapped in pla plga microspheres
Journal of Controlled Release, 2004Co-Authors: Maria J Blancoprieto, M A Campanero, Kamel Besseghir, F Heimgatner, Bruno GanderAbstract:The aim of the work was to develop biodegradable microspheres for controlled delivery of the somatostatin analogue Vapreotide and maintenance of sustained plasma levels over 2-4 weeks after a single injection in rats. Vapreotide was microencapsulated into end-group capped and uncapped low molecular weight poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) by spray-drying and coacervation. Microspheres were prepared from single and blended (1:1) polymer types. The microparticles were characterized for peptide loading, in vitro release and pharmocokinetics in rats. Spray-drying and coacervation produced microspheres in the size range of 1-15 and 10-70 microm, respectively, and with encapsulation efficiencies varying between 46% and 87%. In vitro release of Vapreotide followed a regular pattern and lasted more than 4 weeks, time at which 40-80% of the total dose were released. Microspheres made of 14-kDa end-group uncapped PLGA50:50 or 1:1 blends of this polymer with 35 kDa end-group uncapped PLGA50:50 gave the best release profiles and yielded the most sustained plasma levels above a pre-defined 1 ng/ml over approximately 14 days. In vitro/in vivo correlation analyses showed for several microsphere formulations a linear correlation between the mean residence time in vivo and the mean dissolution time (r=0.958) and also between the amount released between 6 h and 14 days and the AUC(6h-14d) (r=0.932). For several other parameters or time periods, no in vitro/in vivo correlation was found. This study demonstrates that controlled release of the Vapreotide is possible in vivo for a duration of a least 2 weeks when administered i.m. to rats. These results constitute a step forward towards a twice-a-month or once-a-month microsphere-formulation for the treatment of acromegaly and neuroendocrine tumors.
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importance of the test medium for the release kinetics of a somatostatin analogue from poly d l lactide co glycolide microspheres
International Journal of Pharmaceutics, 1999Co-Authors: Maria J Blancoprieto, Kamel Besseghir, Piero Orsolini, Frederic Heimgartner, Christine Deuschel, Hans P Merkle, Ho Namtrân, Bruno GanderAbstract:The determination of in vitro release kinetics of peptides from poly(d,l-lactide-co-glycolide) (PLGA) microspheres generally requires optimization of the test conditions for a given formulation. This is particularly important when in vitro/in vivo correlation should be determined. Here, the somatostatin analogue Vapreotide pamoate, an octapeptide, was microencapsulated into PLGA 50:50 by spray-drying. The solubility of this peptide and its in vitro release kinetics from the microspheres were studied in various test media. The solubility of Vapreotide pamoate was approximately 20-40 microg/ml in 67 mM phosphate buffer saline (PBS) at pH 7.4, but increased to approximately 500-1000 microg/ml at a pH of 3.5. At low pH, the solubility increased with the buffer concentration (1-66 mM). Very importantly, proteins (aqueous bovine serum albumin (BSA) solution or human serum) appeared to solubilize the peptide pamoate, resulting in solubilities ranging from 900 to 6100 microg/ml. The release rate was also greatly affected by the medium composition. Typically, in PBS of pH 7.4, only 33+/-1% of the peptide were released within 4 days, whereas 53+/-2 and 61+/-0.9% were released in 1% BSA solution and serum, respectively. The type of medium was found critical for the estimation of the in vivo release. The in vivo release kinetics of Vapreotide pamoate from PLGA microspheres following administration to rats were qualitatively in good agreement with those obtained in vitro using serum as release medium. Finally, sterilization by gamma-irradiation had only a minor effect on the in vivo pharmacokinetics.
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analysis of the influence of polymer characteristics and core loading on the in vivo release of a somatostatin analogue
European Journal of Pharmaceutical Sciences, 1997Co-Authors: Alexandra Rothenweinhold, Kamel Besseghir, Robert GurnyAbstract:Abstract Peptides and proteins have received much attention in recent years as candidate drugs. Vapreotide (RC-160) is a somatostatin analogue used for the therapy of hormone-dependent tumors and endocrine disorders. Like other peptides, it cannot be administered by the oral route and its plasma half-life is relatively short after parenteral administration. For these reasons, its use would be greatly enhanced by a sustained delivery system capable of maintaining controlled plasma levels of the peptide over an extended period of time. Poly( d,l -lactide-co-glyco (PLGA) are biocompatible biodegradable materials useful for a variety of applications, including the design of controlled-release systems for pharmaceutical agents. RC-160 pamoate loaded implants are proposed in this work as a means for controlling the drug release. Various PLGA were studied as biodegradable drug carriers and their in vivo release profiles were examined. Poly( d,l -lactide-co-glycolide) implants containing RC-160 were prepared by an extrusion method and the drug release was evaluated in vivo in rats using a radioimmunoassay method. The effects on the release profile, obtained by varying molecular weight, lactide/glycolide ratio and core loading were studied. The effects of polymer end groups were also investigated. Gel permeation chromatography was employed to characterize the loss in molecular weight of the different polymers after extrusion and γ-sterilization. It was found that drug loading, polymer molecular weight, copolymer composition and end group modifications were critical factors affecting the in vivo release properties. However, even though complex problems still exist, controlled release of peptides from biodegradable PLGA matrices can be achieved.
Yannic B. Schuetz - One of the best experts on this subject based on the ideXlab platform.
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Transdermal Iontophoretic Delivery of Vapreotide Acetate AcrossPorcine Skin in Vitro
Pharmaceutical Research, 2005Co-Authors: Yannic B. Schuetz, Aarti Naik, Evelyne Vuaridel, Yogeshvar N. KaliaAbstract:Purpose The purpose of this study was to evaluate the feasibility of delivering Vapreotide, a somatostatin analogue, by transdermal iontophoresis. Methods In vitro experiments were conducted using dermatomed porcine ear skin and heat-separated epidermis. In addition to quantifying Vapreotide transport into and across the skin, the effect of peptide delivery on skin permselectivity was also measured. The influence of (1) current density, (2) pre- and post-treatment of the skin, (3) competitive ions, and (4) inclusion of albumin in the receptor on Vapreotide delivery were investigated. Results Epidermis proved to be a better model than dermatomed skin for Vapreotide transport studies. Despite the susceptibility of Vapreotide to enzymatic degradation, a flux of 1.7 μg/cm^2 per hour was achieved after 7 h of constant current iontophoresis (0.15 mA/cm^2). Post-iontophoretic extraction revealed that, depending on the experimental conditions, 80–300 μg of peptide were bound to the skin. Vapreotide was found to interact with the skin and displayed a current-dependent inhibition of electroosmosis. However, neither the pre-treatment strategies to saturate the putative binding sites nor the post-treatment protocols to displace the bound peptide were effective. Conclusion Based on the observed transport rate of Vapreotide across porcine epidermis and its clinical pharmacokinetics, therapeutic concentrations should be achievable using a 15-cm^2 patch.
Maria J Blancoprieto - One of the best experts on this subject based on the ideXlab platform.
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importance of single or blended polymer types for controlled in vitro release and plasma levels of a somatostatin analogue entrapped in pla plga microspheres
Journal of Controlled Release, 2004Co-Authors: Maria J Blancoprieto, M A Campanero, Kamel Besseghir, F Heimgatner, Bruno GanderAbstract:The aim of the work was to develop biodegradable microspheres for controlled delivery of the somatostatin analogue Vapreotide and maintenance of sustained plasma levels over 2-4 weeks after a single injection in rats. Vapreotide was microencapsulated into end-group capped and uncapped low molecular weight poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) by spray-drying and coacervation. Microspheres were prepared from single and blended (1:1) polymer types. The microparticles were characterized for peptide loading, in vitro release and pharmocokinetics in rats. Spray-drying and coacervation produced microspheres in the size range of 1-15 and 10-70 microm, respectively, and with encapsulation efficiencies varying between 46% and 87%. In vitro release of Vapreotide followed a regular pattern and lasted more than 4 weeks, time at which 40-80% of the total dose were released. Microspheres made of 14-kDa end-group uncapped PLGA50:50 or 1:1 blends of this polymer with 35 kDa end-group uncapped PLGA50:50 gave the best release profiles and yielded the most sustained plasma levels above a pre-defined 1 ng/ml over approximately 14 days. In vitro/in vivo correlation analyses showed for several microsphere formulations a linear correlation between the mean residence time in vivo and the mean dissolution time (r=0.958) and also between the amount released between 6 h and 14 days and the AUC(6h-14d) (r=0.932). For several other parameters or time periods, no in vitro/in vivo correlation was found. This study demonstrates that controlled release of the Vapreotide is possible in vivo for a duration of a least 2 weeks when administered i.m. to rats. These results constitute a step forward towards a twice-a-month or once-a-month microsphere-formulation for the treatment of acromegaly and neuroendocrine tumors.
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importance of the test medium for the release kinetics of a somatostatin analogue from poly d l lactide co glycolide microspheres
International Journal of Pharmaceutics, 1999Co-Authors: Maria J Blancoprieto, Kamel Besseghir, Piero Orsolini, Frederic Heimgartner, Christine Deuschel, Hans P Merkle, Ho Namtrân, Bruno GanderAbstract:The determination of in vitro release kinetics of peptides from poly(d,l-lactide-co-glycolide) (PLGA) microspheres generally requires optimization of the test conditions for a given formulation. This is particularly important when in vitro/in vivo correlation should be determined. Here, the somatostatin analogue Vapreotide pamoate, an octapeptide, was microencapsulated into PLGA 50:50 by spray-drying. The solubility of this peptide and its in vitro release kinetics from the microspheres were studied in various test media. The solubility of Vapreotide pamoate was approximately 20-40 microg/ml in 67 mM phosphate buffer saline (PBS) at pH 7.4, but increased to approximately 500-1000 microg/ml at a pH of 3.5. At low pH, the solubility increased with the buffer concentration (1-66 mM). Very importantly, proteins (aqueous bovine serum albumin (BSA) solution or human serum) appeared to solubilize the peptide pamoate, resulting in solubilities ranging from 900 to 6100 microg/ml. The release rate was also greatly affected by the medium composition. Typically, in PBS of pH 7.4, only 33+/-1% of the peptide were released within 4 days, whereas 53+/-2 and 61+/-0.9% were released in 1% BSA solution and serum, respectively. The type of medium was found critical for the estimation of the in vivo release. The in vivo release kinetics of Vapreotide pamoate from PLGA microspheres following administration to rats were qualitatively in good agreement with those obtained in vitro using serum as release medium. Finally, sterilization by gamma-irradiation had only a minor effect on the in vivo pharmacokinetics.
