Poly(L-glutamic acid) Microsphere: Preparation and Application in Oral Drug Controlled Release

Abstract

Poly(L-glutamic acid) (PLG) and its derivatives, which are biodegradable and biocompatible, are one kind of the most widely investigated synthetic polypeptides as biomedical materials benefited from their pH-responsive property (pKa~ 4.1) and modifiable side carboxyl group. In this work, PLG was synthesized via a two-step procedure. Poly(γ-benzyl-L-glutamate) (PBLG) was first synthesized by the ring-opening polymerization of γ-benzyl-L-glutamate-N-carboxyanhydride (BLG-NCA) using n-hexylamine as initiator, and then PLG was prepared by the deprotection of benzyl groups in PBLG. PLG microsphere was prepared by the oil-in-oil (O/O) anhydrous emulsion method utilizing N,N-dimetylformamide as an inner oil phase and corn oil as an outer oil phase. Rifampicin, a model drug, was load- ed into the PLG microsphere, and the drug loading capacity and entrapment efficiency were revealed. The scanning electron microscopy micrograph indicated that the drug-loaded microsphere exhibited spherical morphology with narrow size distri- bution and average diameter at about 9.0 μm. To investigate the application of PLG microsphere in oral drug delivery (espe- cially for enteric-coated drugs), the in vitro rifampicin release experiments in simulated gastric or intestinal fluid were per- formed. In vitro release results revealed that the release of rifampicin from microsphere was highly dependent on pH. In de- tail, less amount of rifampicin was released in simulated gastric fluid, while the quicker release of rifampicin occurred in simulated intestinal fluid. It was because that the deprotonation of carboxyl groups in PLG caused the loose, expansion, and even disintegration of PLG microsphere in simulated intestinal fluid. Moreover, the morphology of microsphere in simulated gastric fluid was different from that in simulated intestinal fluid, which further confirmed the pH-sensitive property of mi- crosphere. Additionally, in vitro methyl thiazolyl tetrazolium assays demonstrated that the PLG microsphere was biocompat- ible. Therefore, the biocompatible PLG microsphere with the intelligent pH-triggered drug release should be promising for application in oral drug delivery. Keywords enteric carrier; poly(L-glutamic acid); oral administration; microsphere; drug delivery