Formulation of controlled-release delivery systems for the alpha-melanocyte stimulating hormone analog, Melanotan-I

Persistent Link:
http://hdl.handle.net/10150/282435
Title:
Formulation of controlled-release delivery systems for the alpha-melanocyte stimulating hormone analog, Melanotan-I
Author:
Bhardwaj, Renu, 1968-
Issue Date:
1997
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
The overall objective of this research was to develop controlled-release formulations of Melanotan-I (MT-I). Two polymers were used, Poloxamer 407 (P407) and Poly(D,L lactide-co-glycolide) (PLGA). First, various aqueous formulations of P407 were evaluated containing MT-I and 25% w/v P407 alone, or with one of the following additives present, i.e., polyvinylpyrrolidone, methylcellulose or hydroxypropyl methylcellulose. The in-vitro release profiles of MT-I from the P407 formulations and the dissolution of the gel were obtained simultaneously using a membraneless in vitro model and a zero-order profile was observed for both. The in-vivo release kinetics of selected formulations were analyzed in guinea pigs following intraperitoneal administration. The plasma concentration-time profiles showed an extended release of the peptide formulated with gel compared to the interperitoneal administration of MT-I in solution and exhibited potential for prolonged release up to 24 hrs only. Biodegradable implants of PLGA copolymer were prepared by a melt-extrusion method. The in vitro release of MT-I from the implants exhibited a triphasic profile with an initial rapid release followed by a secondary phase of slow release, then a tertiary phase of rapid release due to erosion of the polymer. Based on release kinetics of MT-I from different viscosity PLGA implants, the polymer having a viscosity of 0.6 dL/gm was selected for preparing an implant system with a one-month duration of release. Molecular weight reduction, mass loss and lactic acid release from PLGA implants were characterized in order to correlate the in vitro release profile of MT-I with hydrolytic degradation of the polymer. The in vivo release profile of the MT-I depot implanted subcutaneously exhibited a one-month release of the peptide and the reflectance reading obtained from a reflectometer showed a prolonged skin darkening for 3 months. A 2.5 fold increase in the melanin pigment (eumelanin) was observed in guinea pig skin biopsy samples. The results indicate that the PLGA implants are a promising delivery device for controlled-release of MT-I over a one-month period.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Health Sciences, Pharmacy.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Pharmacy Practice and Science
Degree Grantor:
University of Arizona
Advisor:
Blanchard, James

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleFormulation of controlled-release delivery systems for the alpha-melanocyte stimulating hormone analog, Melanotan-Ien_US
dc.creatorBhardwaj, Renu, 1968-en_US
dc.contributor.authorBhardwaj, Renu, 1968-en_US
dc.date.issued1997en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractThe overall objective of this research was to develop controlled-release formulations of Melanotan-I (MT-I). Two polymers were used, Poloxamer 407 (P407) and Poly(D,L lactide-co-glycolide) (PLGA). First, various aqueous formulations of P407 were evaluated containing MT-I and 25% w/v P407 alone, or with one of the following additives present, i.e., polyvinylpyrrolidone, methylcellulose or hydroxypropyl methylcellulose. The in-vitro release profiles of MT-I from the P407 formulations and the dissolution of the gel were obtained simultaneously using a membraneless in vitro model and a zero-order profile was observed for both. The in-vivo release kinetics of selected formulations were analyzed in guinea pigs following intraperitoneal administration. The plasma concentration-time profiles showed an extended release of the peptide formulated with gel compared to the interperitoneal administration of MT-I in solution and exhibited potential for prolonged release up to 24 hrs only. Biodegradable implants of PLGA copolymer were prepared by a melt-extrusion method. The in vitro release of MT-I from the implants exhibited a triphasic profile with an initial rapid release followed by a secondary phase of slow release, then a tertiary phase of rapid release due to erosion of the polymer. Based on release kinetics of MT-I from different viscosity PLGA implants, the polymer having a viscosity of 0.6 dL/gm was selected for preparing an implant system with a one-month duration of release. Molecular weight reduction, mass loss and lactic acid release from PLGA implants were characterized in order to correlate the in vitro release profile of MT-I with hydrolytic degradation of the polymer. The in vivo release profile of the MT-I depot implanted subcutaneously exhibited a one-month release of the peptide and the reflectance reading obtained from a reflectometer showed a prolonged skin darkening for 3 months. A 2.5 fold increase in the melanin pigment (eumelanin) was observed in guinea pig skin biopsy samples. The results indicate that the PLGA implants are a promising delivery device for controlled-release of MT-I over a one-month period.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectHealth Sciences, Pharmacy.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePharmacy Practice and Scienceen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorBlanchard, Jamesen_US
dc.identifier.proquest9806824en_US
dc.identifier.bibrecord.b37555789en_US
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