Chitosan coated vancomycin hydrochloride liposomes: Characterizations and evaluation.
The present work evaluated the feasibility of chitosan coated liposomes (c-Lips) for the intravenous delivery of vancomycin hydrochloride (VANH), a water-soluble antibiotic for the treatment of gram-positive bacterial infections like osteomyelitis, arthritis, endocarditis, pneumonia, etc. The objective of this research was to develop a suitable drug delivery system in vivo which could improve therapeutic efficacy and decrease side effects especially nephrotoxicity. Firstly, the vancomycin hydrochloride liposomes (VANH-Lips) were prepared by modified reverse phase evaporation method, then the chitosan wrapped vancomycin hydrochloride liposomes (c-VANH-Lips) nanosuspension was formulated by the method of electrostatic deposition. Based on the optimized results of single-factor screening experiment, the c-VANH-Lips were found to be relatively uniform in size (220.40 ± 3.56 nm) with a narrow polydispersity index (PI) (0.21 ± 0.03) and a positive zeta potential (25.7 ± 1.12 mV). The average drug entrapment efficiency (EE) and drug loading (DL) were 32.65 ± 0.59% and 2.18 ± 0.04%, respectively. The in vitro release profile of c-VANH-Lips possessed a sustained release Characterization and the release behavior was in accordance with the Weibull equation. Hemolysis experiments showed that its intravenous injection had preliminary safety. In vivo, after intravenous injection to mice, c-VANH-Lips showed a longer retention time and higher AUC values compared with the VANH injection (VANH-Inj) and VANH-Lips. In addition, biodistribution results clearly demonstrated that c-VANH-Lips preferentially decreased the drug distribution in kidney of mice after intravenous injection. These results revealed that injectable c-VANH-Lips may serve as a promising carrier for VANH to increase therapeutic efficacy on gram-positive bacterial infections and reduce nephrotoxicity, which provides significantly clinical value for long-term use of VANH.
School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Jinan 250012, China.
Zhenlei
Z
Yang
School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Jinan 250012, China.
Junli
J
Liu
School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Jinan 250012, China.
Jinhua
J
Gao
School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Jinan 250012, China.
Shilei
S
Chen
School of Pharmaceutical Sciences, Shandong University, 44 Wenhua Xi Road, Jinan 250012, China. Electronic address: hgh2003@gmail.com.
Guihua
G
Huang
D061605:Administration, Intravenous; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005612:Freeze Drying; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D010316:Particle Size; D012995:Solubility; D013499:Surface Properties; D014018:Tissue Distribution; D014640:Vancomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics
D004337:Drug Carriers; D008081:Liposomes; D014640:Vancomycin; D048271:Chitosan
Chitosan (PubChem CID: 21896651); Chitosan wrapped liposomes; Cholesterol (PubChem CID: 5997); Gram-positive bacterial infections; In vitro release; Pharmacokinetic; Phosphatidylcholine (PubChem CID: 52922418); Tissue distribution; Vancomycin hydrochloride; Vancomycin hydrochloride (PubChem CID: 6420023)