title: Design of physostigmine-loaded polymeric microparticles for pretreatment against exposure to organophosphate agents.
abstract: Physostigmine is an anti-cholinesterase used for the pretreatment of a poisoning caused by highly toxic organophosphorus neurotoxins. The aim of this study is to design a polymeric microparticle system for sustained release of physostigmine. In this paper, we have attempted to encapsulate physostigmine in microparticles made from poly(D,L-lactide-co-glycolide) (PLGA) with various contents of glycolide and poly(D,L-lactide) (PLA) using spray-drying and single emulsion techniques. It was found that during the single emulsion process, most of the physostigmine molecules were lost in the external aqueous phase. However, more than 90% encapsulation efficiency of physostigmine was obtained using the spray-drying technique. SEM micrographs revealed that spherical microparticles containing physostigmine with a smooth surface were yielded with PLA, PLGA 50:50, RG 502 (PLGA 50:50 with a lower molecular weight) and PLGA 65:35 but PLGA 85:15, PLGA 75:25 and PLGA 50:50 with a high concentration produced microparticles with irregular shapes. An increased inlet temperature yielded a higher physostigmine release rate from the PLA microparticles. Physostigmine release from the microparticles showed a biphasic pattern, characterized by an initial burst release followed by a sustained release for PLGA 65:35, PLGA 50:50 and RG 502 or a non-detectable release for PLGA 85:15, PLGA 75:25 and PLA. A sustained-release of physostigmine with a low initial burst over 1 week was achieved from RG 502 microparticles, which would be used as an injectable dosage form in our further animal studies.
authors.affiliation: Institute of Materials Research and Engineering, National University of Singapore, No. 3 Research Link, 117602, Singapore, Singapore.
authors.forename: Cheng Shu
authors.initials: CS
authors.lastname: Chaw
authors.forename: Cherng Wen
authors.initials: CW
authors.lastname: Tan
authors.forename: Yi Yan
authors.initials: YY
authors.lastname: Yang
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.forename: Shabbir
authors.initials: S
authors.lastname: Moochhala
mesh_terms: D001704:Biopolymers / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage*; D007306:Insecticides / Q000037:antagonists & inhibitors / Q000633:toxicity; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D009943:Organophosphorus Compounds; D010316:Particle Size; D010830:Physostigmine / Q000008:administration & dosage*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D012995:Solubility
chemical_list: D001704:Biopolymers; D002800:Cholinesterase Inhibitors; D007306:Insecticides; D009943:Organophosphorus Compounds; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D010830:Physostigmine