title: Synthesis, characterization, drug-loading capacity and safety of novel pH-independent amphiphilic amino acid copolymer micelles.
abstract: A novel block copolymer containing two polymeric components, poly(L-aspartic acid)-b-poly (L-phenylalanine) (PAA-PPA), was synthesized and its potential for the preparation of copolymer micelles with a poorly water-soluble drug was investigated in this study. The chemical structure and physical properties of PAA-PPA were characterized by FTIR, 1H NMR and TG. The degree of polymerization of PAA-PPA was calculated by analyzing the relative area of N-CH signal and C-CH3 of 1H NMR spectra. The critical micelle concentration (CMC) of the PAA-PPA achieved a minimum of 11.1 mg/L. Studies on the drug-free PAA-PPA solutions showed PAA-PPA aggregation into micellar type in the sub-150 nm size range. Furthermore, the size of the PAA-PPA micelles was found to be pH-independent between the pH range of 4.0 and 8.0, which could be favorable to avoid the limitation of the size change at the specified pH value seeking drug stability. 4-amino-2-trifluoromethyl-phenyl retinate (ATPR) was studied as a poorly water-soluble model drug. The drug-loading and entrapment efficiency of the ATPR-loaded PAA-PPA micelles were 30.9 wt% and 87.9 %, respectively. The high drug-loading and entrapment efficiency were due to the synergistic effect of the micellar encapsulation and the binding interaction between drug and PAA-PPA. The ATPR-loaded PAA-PPA micelles showed a narrow size distribution, low zeta potential, high drug-loading capacity and good stable. The PAA-PPA was safer than Tween-80 and Cremophor EL (CrmEL) as an injectable pharmaceutical adjuvant for ATPR as indicated by the hemolysis and cytotoxicity studies. The novel amphiphilic amino acid copolymer can be considered as a prospective injectable delivery system for ATPR in terms of the pH-independent, greater drug-loading capacity and safety.
authors.affiliation: Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China.
authors.forename: Jihui
authors.initials: J
authors.lastname: Tang
authors.forename: Jing
authors.initials: J
authors.lastname: Yao
authors.forename: Jingbo
authors.initials: J
authors.lastname: Shi
authors.forename: Qingpin
authors.initials: Q
authors.lastname: Xiao
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhou
authors.forename: Feihu
authors.initials: F
authors.lastname: Chen
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D004355:Drug Stability; D004563:Electrochemistry; D006461:Hemolysis / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008823:Micelles; D008970:Molecular Weight; D010316:Particle Size; D010455:Peptides / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011817:Rabbits; D012995:Solubility
chemical_list: D000596:Amino Acids; D004337:Drug Carriers; D007202:Indicators and Reagents; D008823:Micelles; D010455:Peptides; D011108:Polymers; C017645:polyaspartate; C012001:polyphenylalanine