caa a22 4500 445312378 CHVBK 20180317142634.0 cr unu---uuuuu 170323e20110701xx s 000 0 eng 10.1007/s11095-011-0409-6 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0409-6 PLGA Microparticles Encapsulating Prostaglandin E1-Hydroxypropyl-β-cyclodextrin (PGE1-HPβCD) Complex for the Treatment of Pulmonary Arterial Hypertension (PAH) [Elektronische Daten] [Vivek Gupta, Marauo Davis, Louisa Hope-Weeks, Fakhrul Ahsan] ABSTRACT: Purpose: To test the efficacy and viability of poly (lactic-co-glycolic acid) (PLGA) microspheres encapsulating an inclusion complex of prostaglandin E1 (PGE1) and 2-hydroxypropyl-β-cyclodextrin (HPβCD) for pulmonary delivery of PGE1 for treatment of pulmonary arterial hypertension (PAH), a disease of pulmonary circulation. Methods: PLGA-based microparticulate formulations of PGE1-HPβCD inclusion complex or plain PGE1 were prepared by a double-emulsion solvent evaporation method. HPβCD was used as a complexing agent to increase the aqueous solubility of PGE1, act as a porosigen to produce large porous particles, and promote absorption of PGE1. 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 5μm. 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 PGE1 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 PGE1-HPβCD complex encapsulated in PLGA microparticles as a potential delivery system for controlled release of inhaled PGE1. Springer Science+Business Media, LLC, 2011 microparticles nationallicence poly (lactic- co -glycolic acid) nationallicence prostaglandin E1 nationallicence pulmonary arterial hypertension nationallicence pulmonary delivery nationallicence 2-hydroxypropyl-β-cyclodextrin nationallicence Gupta Vivek Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter Drive, 79106, Amarillo, Texas, USA aut Davis Marauo Department of Chemistry and Biochemistry, Texas Tech University, Memorial Circle and Boston, 79409, Lubbock, Texas, USA aut Hope-Weeks Louisa Department of Chemistry and Biochemistry, Texas Tech University, Memorial Circle and Boston, 79409, Lubbock, Texas, USA aut Ahsan Fakhrul Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter Drive, 79106, Amarillo, Texas, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/7(2011-07-01), 1733-1749 0724-8741 28:7<1733 2011 28 11095 https://doi.org/10.1007/s11095-011-0409-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0409-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gupta Vivek Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter Drive, 79106, Amarillo, Texas, USA aut NATIONALLICENCE 700 1- Davis Marauo Department of Chemistry and Biochemistry, Texas Tech University, Memorial Circle and Boston, 79409, Lubbock, Texas, USA aut NATIONALLICENCE 700 1- Hope-Weeks Louisa Department of Chemistry and Biochemistry, Texas Tech University, Memorial Circle and Boston, 79409, Lubbock, Texas, USA aut NATIONALLICENCE 700 1- Ahsan Fakhrul Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter Drive, 79106, Amarillo, Texas, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/7(2011-07-01), 1733-1749 0724-8741 28:7<1733 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer