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Inducing Controlled Release and Increased Tumor-Targeted Delivery of Chlorambucil via Albumin/Liposome Hybrid Nanoparticles.
- Source :
-
AAPS PharmSciTech [AAPS PharmSciTech] 2017 Nov; Vol. 18 (8), pp. 2977-2986. Date of Electronic Publication: 2017 May 05. - Publication Year :
- 2017
-
Abstract
- Liposomes possess good biocompatibility and excellent tumor-targeting capacity. However, the rapid premature release of lipophilic drugs from the lipid bilayer of liposomes has negative effect on the tumor-targeted drug delivery of liposomes. In this study, a lipophilic antitumor drug-chlorambucil (CHL)-was encapsulated into the aqueous interior of liposomes with the aid of albumin to obtain the CHL-loaded liposomes/albumin hybrid nanoparticles (CHL-Hybrids). The in vitro accumulative release rate of CHL from CHL-Hybrids was less than 50% within 48 h, while the accumulative CHL release was more than 80% for CHL-loaded liposomes (CHL-Lip). After intravenous injection into rats, the half-life (t <subscript>1/2β</subscript>  = 5.68 h) and maximum blood concentration (C <subscript>max</subscript>  = 4.58 μg/mL) of CHL-Hybrids were respectively 1.1 times and 3.5 times higher than that of CHL-Lip. In addition, CHL-Hybrids had better tumor-targeting capacity for it significantly increased the drug accumulation in B16F10 tumors, which contributed to the significantly control of tumor growth compared with CHL-Lip. Furthermore, CHL-Hybrid-treated B16F10 melanoma-bearing mice displayed the longest median survival time of 30.0 days among all the treated groups. Our results illustrated that the proposed hybrids drug delivery system would be a promising strategy to maintain the controlled release of lipophilic antitumor drugs from liposomes and simultaneously facilitate the tumor-targeted drug delivery.
- Subjects :
- Animals
Antineoplastic Agents, Alkylating administration & dosage
Cell Line, Tumor
Chlorambucil administration & dosage
Delayed-Action Preparations administration & dosage
Delayed-Action Preparations metabolism
Humans
Liposomes
Melanoma, Experimental drug therapy
Mice
Mice, Inbred C57BL
Nanoparticles administration & dosage
Neoplasms
Particle Size
Rats
Rats, Wistar
Serum Albumin administration & dosage
Tumor Burden drug effects
Tumor Burden physiology
Xenograft Model Antitumor Assays methods
Antineoplastic Agents, Alkylating metabolism
Chlorambucil metabolism
Drug Delivery Systems methods
Nanoparticles metabolism
Serum Albumin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1530-9932
- Volume :
- 18
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- AAPS PharmSciTech
- Publication Type :
- Academic Journal
- Accession number :
- 28477146
- Full Text :
- https://doi.org/10.1208/s12249-017-0782-5