TY - JOUR
T1 - PLGA microparticles encapsulating prostaglandin E 1- hydroxypropyl-β-cyclodextrin (PGE 1-HPβCD) complex for the treatment of Pulmonary Arterial Hypertension (PAH)
AU - Gupta, Vivek
AU - Davis, Marauo
AU - Hope-Weeks, Louisa J.
AU - Ahsan, Fakhrul
N1 - Funding Information:
The authors sincerely thank Mr. Charles Linch at the Department of Medical Photography and Electron Microscopy Texas Tech University Health Sciences Center, Lubbock, TX, for his help with the scanning electron microscopy experiments. This work was supported by an American Recovery and Reinvestment Act Fund, NIH 1R15HL103431 (FA).
PY - 2011/7
Y1 - 2011/7
N2 - 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.
AB - 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.
KW - 2-hydroxypropyl-β- cyclodextrin
KW - microparticles.
KW - poly (lactic-co-glycolic acid)
KW - prostaglandin E
KW - pulmonary arterial hypertension
KW - pulmonary delivery
UR - http://www.scopus.com/inward/record.url?scp=79959871129&partnerID=8YFLogxK
U2 - 10.1007/s11095-011-0409-6
DO - 10.1007/s11095-011-0409-6
M3 - Article
C2 - 21626061
AN - SCOPUS:79959871129
SN - 0724-8741
VL - 28
SP - 1733
EP - 1749
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 7
ER -