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PLGA Microparticles Encapsulating Prostaglandin E(1)-Hydroxypropyl-β-cyclodextrin (PGE (1)-HPβCD) Complex for the Treatment of Pulmonary Arterial Hypertension (PAH).
MedLine Citation:
PMID:  21626061     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE: To test the efficacy and viability of poly (lactic-co-glycolic acid) (PLGA) microspheres encapsulating an inclusion complex of prostaglandin E(1) (PGE(1)) and 2-hydroxypropyl-β-cyclodextrin (HPβCD) for pulmonary delivery of PGE(1) for treatment of pulmonary arterial hypertension (PAH), a disease of pulmonary circulation. METHODS: PLGA-based microparticulate formulations of PGE(1)-HPβCD inclusion complex or plain PGE(1) were prepared by a double-emulsion solvent evaporation method. HPβCD was used as a complexing agent to increase the aqueous solubility of PGE(1), act as a porosigen to produce large porous particles, and promote absorption of PGE(1). Particles were characterized for micromeritic properties, in vivo absorption, metabolic degradation, and acute safety. RESULTS: Incorporation of HPβCD in the microparticles resulted in development of large particles with internal pores, which, despite large mean diameters, had aerodynamic diameters in the inhalable range of 1 to 5 μm. HPβCD incorporation also resulted in a significant increase in the amount of drug released in vitro in simulated interstitial lung fluid, showing a desirable burst release profile required for immediate hemodynamic effects. Compared to plain PLGA microparticles, entrapment efficiency was decreased upon complexation with HPβCD. In vivo absorption profile indicated prolonged availability of PGE(1) in circulation following pulmonary administration of the optimized microparticulate formulations, with an extended half-life of almost 4 hours. Metabolic degradation and acute toxicity studies suggested that microparticulate formulations were stable under physiological conditions and safe for the lungs and respiratory epithelium. CONCLUSIONS: This study demonstrates the feasibility of PGE(1)-HPβCD complex encapsulated in PLGA microparticles as a potential delivery system for controlled release of inhaled PGE(1).
Authors:
Vivek Gupta; Marauo Davis; Louisa J Hope-Weeks; Fakhrul Ahsan
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-6
Journal Detail:
Title:  Pharmaceutical research     Volume:  -     ISSN:  1573-904X     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-5-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter Drive, Amarillo, Texas, 79106, USA.
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