Synthesis and Biopharmaceutical Characterisation of a New Poly hydroxyethyl
X-H Qi, W. Lin, Q. He, X-H Guan
Nanjing Medical University, CN
Keywords: poly aspartic acid, copolymer, polymeric nano-carrier drug, drug release
Abstract:A promising approach to improve drug delivery is to modify a polymeric backbone structure by means of copolymerization. Such obtained macromolecular prodrugs (polymer–drug conjugates) may offer many advantages compared to other drug delivery systems: increased drug solubility, prolonged drug release, more convenient drug regiment, increased stability and targetability. The aim of this research was the preparation of new drug carriers possessing the advantageous properties of the starting polymer and peculiar performances in mucosal drug delivery, which enlarges our previous studies[1,2]. In this paper the poly aspartic acid-co-glutamic acid (PAG) was prepared by acid catalysed polycondensation the mixture of aspartic acid and glutamic acid in mixture solvents of trimethylbenzene and sulfolane. The metronidazole(MTZ) was attached to PAG via an ester bond by using dicyclohexylcarbodiimide(DCC) and N,N-dimethylaminopyridine(DMAP) to form copolymeric nano-carrier drug(PAG-MTZ). The obtained PAG-MTZ have been characterized by infrared spectrum(IR), hydrogen nuclear magnetic resonance(1H-NMR), gel permeation chromatography(GPC), ultraviolet spectrum (UV), transmission electron microscope(TEM), and particle size distribution analysis. The results showed the spherical shaps of PAG-MTZ was random copolymers, average molecular weight was 14281g•mol-1, the diameter of the particle was 198.9nm with a narrow size distribution, the drug loadings were about 12%, and the stability of the drug in laboratory was higher, water absorption rate was exceeded 20%. In vitro drug release properties of the MTZ loading in the PAG-MTZ copolymeric nano-carrier drug in simulated vaginal fluids were showed to be sustained obviously. The accumulation percentage of metronidazole was 12.19% at 1 hour after released, and 47.51% at 24 hour while the MTZ releasing about 100%. In vivo PAG-MTZ were determined with high performance liquid chromatography(HPLC), the resules showed 2.18 times t1/2(half time) and 3.87 times MRT(mean residence time) longer than MTZ active compound in cervix and vagina. It is concluded that PAG, as a delivery system, could increased solubility and prolonged drug release, and be potentially useful for treatment of Trichomonas vaginitis, one of the most prevalent nonviral sexually transmitted disease.