ABSTRACT
BACKGROUND/AIM: Polymeric micelles are promising vehicles for paclitaxel delivery. Further improvement in the stability of the micelle formulation is desirable. MATERIALS AND METHODS: Monomethoxy poly(ethylene glycol)-block-poly(D,L-lactide)-9-fluorenylmethoxycarbonyl-L-phenylalanine (mPEG-PDLLA-Phe(Fmoc)) was synthesized through a classical esterification reaction. Paclitaxel-loaded mPEG-PDLLA-Phe(Fmoc) micelles (PTX-PheMs) were prepared by the self-assembly method. Composition, structure and physicochemical properties were characterized. Pharmacokinetics were evaluated in rats. Therapeutic effect was evaluated in tumor-bearing mice. Safety profile was assessed by a hemolysis assay and an acute-toxicity study. RESULTS: The average size of PTX-PheMs was about 45 nm. The hemolysis and acute-toxicity tests confirmed its biocompatibility and safety. The pharmacokinetics and therapeutic effect experiments demonstrated its long circulation property and superior antitumor effect. CONCLUSION: mPEG-PDLLA-Phe(Fmoc) micelle is a biocompatible and effective drug delivery system for hydrophobic drugs such as PTX.
Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Drug Delivery Systems , Micelles , Paclitaxel/administration & dosage , Polymers/administration & dosage , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacokinetics , Antineoplastic Agents, Phytogenic/therapeutic use , Cell Line, Tumor , Hemolysis/drug effects , Humans , Male , Mice, Nude , Neoplasms/drug therapy , Neoplasms/pathology , Paclitaxel/chemistry , Paclitaxel/pharmacokinetics , Paclitaxel/therapeutic use , Particle Size , Polymers/chemistry , Polymers/pharmacokinetics , Polymers/therapeutic use , Rats, Sprague-Dawley , Tumor Burden/drug effectsABSTRACT
BACKGROUND: Due to use of Tween-80 as an enhancer of solubility, the current clinical formulation of cabazitaxel (CBT) (Jevtana®) causes hypersensitivity, neurotoxicity and other severe side-effects. To reduce these vehicle-related effects, a suitable nanocarrier is needed. MATERIALS AND METHODS: Human serum albumin (HSA) was used to encapsulate CBT by a simple self-assembly method. Physicochemical properties of HSA-CBT nanoparticles were characterized. In vitro release property and cytotoxicity were also determined. In vivo imaging system was used to study nanocarrier distribution in vivo. The safety profile was assessed by hemolysis and acute-toxicity study. Finally, the antitumor efficacy in vivo was investigated in tumor-bearing mice. RESULTS: The average size of HSA-CBT nanoparticles was about 240 nm and the encapsulation efficiency reached 97%. The hemolysis and acute-toxicity experiments confirmed biocompatibility of HSA-CBT nanoparticles. CONCLUSION: HSA nanoparticles are a safe and effective drug delivery system for hydrophobic anticancer drugs such as CBT.
