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Synthesis, characterization, drug-loading capacity and safety of novel octyl modified serum albumin micelles.

Abstract
A novel albumin derivative octyl modified serum albumin (OSA) which can form a core-shell structure in aqueous media by self-assembling due to core segregation and a combination of intermolecular forces has been synthesized. The chemical structure and physical properties of OSA were characterized by FTIR, (1)H NMR and TG. The degree of substitution (DS) was in the range of 52.4-69.7% and 48.9-65.8% determined by elemental analysis and fluorescamine assay, respectively. With the increase in the DS of octyl group, the critical micelle concentration (CMC) decreased from 30.1 to 14.7 mg/L because of the increasing hydrophobicity. In the light of the hydrophobic core as a microreservoir for poorly water-soluble drugs, paclitaxel (PTX) was successfully loaded into OSA micelles by the dialysis method with a high drug-loading (33.1 wt%) and entrapment efficiency (90.5%) due to the synergistic effect of micellar encapsulation and binding interaction between drug and OSA. Compared with PTX-loaded unmodified BSA preparation, PTX-loaded OSA micelles are characterized by small size, narrow size distribution, great drug-loading capacity and enhanced stability. The size of PTX-loaded micelles was in the range of 123.3-152.8 nm and smaller than their corresponding blank micelles. Hemolysis and cytotoxicity studies showed that OSA was safer than Tween-80 and Cremophor EL as an injectable pharmaceutic adjuvant for PTX. In terms of the greater drug-loading capacity and safer character, the novel albumin derivative OSA is a prospective injectable delivery system for PTX.
AuthorsJian Gong, Meirong Huo, Jianping Zhou, Yong Zhang, Xiaoling Peng, Di Yu, Hui Zhang, Jing Li
JournalInternational journal of pharmaceutics (Int J Pharm) Vol. 376 Issue 1-2 Pg. 161-8 (Jul 6 2009) ISSN: 1873-3476 [Electronic] Netherlands
PMID19409461 (Publication Type: Evaluation Studies, Journal Article)
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Drug Carriers
  • Micelles
  • Serum Albumin
  • Paclitaxel
Topics
  • Animals
  • Antineoplastic Agents, Phytogenic (administration & dosage, adverse effects)
  • Cell Line, Tumor
  • Cell Survival (drug effects)
  • Drug Carriers (adverse effects, chemical synthesis, chemistry)
  • Drug Delivery Systems (methods)
  • Hemolysis (drug effects)
  • Humans
  • Micelles
  • Paclitaxel (administration & dosage, adverse effects)
  • Rabbits
  • Serum Albumin (chemistry)

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