Design of physostigmine-loaded polymeric microparticles for pretreatment against exposure to organophosphate agents.
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.
Chaw
Cheng Shu
CS
Institute of Materials Research and Engineering, National University of Singapore, No. 3 Research Link, 117602, Singapore, Singapore.
Tan
Cherng Wen
CW
Yang
Yi Yan
YY
Wang
Ling
L
Moochhala
Shabbir
S
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
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