Preparation and in vitro characterization of SN-38-loaded, self-forming polymeric depots as an injectable drug delivery system

J Pharm Sci. 2012 Oct;101(10):3708-17. doi: 10.1002/jps.23238. Epub 2012 Jul 6.

Abstract

This work describes the preparation and characterization of anticancer-loaded injectable polymeric depots that consisted of D,L-lactide (LA), ε-caprolactone (CL), and poly(ethylene glycol) (PEG) or [poly(ε-caprolactone)-random-poly(D,L-lactide)]-block-poly(ethylene glycol)-block-[poly(ε-caprolactone)-random-poly(D,L-lactide)] (PLEC) copolymers for malignant gliomas treatment. PLECs were polymerized with different percentages of LA to deliver 7-ethyl-10-hydroxycamptothecin (SN-38), a highly potent anticancer drug. SN-38-loaded depots could form directly in phosphate buffer saline with more than 98% encapsulation efficiency. The release rate of SN-38 from depots was found to depend on the amount of LA in PLECs, loading content of SN-38 in the depots, and depot weight. Encapsulation of SN-38 inside depots could enhance the stability of SN-38 where all of SN-38 released after 60 days was in an active form. Depots without SN-38 were evaluated as noncytotoxic against U-87MG, whereas SN-38-loaded depots showed cytotoxic effect as a function of concentration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / chemistry*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives*
  • Camptothecin / chemistry
  • Caproates / administration & dosage
  • Caproates / chemistry
  • Cell Line, Tumor
  • Drug Delivery Systems / methods
  • Drug Stability
  • Glioblastoma / drug therapy
  • Humans
  • Irinotecan
  • Kinetics
  • Lactones / administration & dosage
  • Lactones / chemistry
  • Polyesters / administration & dosage
  • Polyesters / chemistry
  • Polyethylene Glycols / administration & dosage
  • Polyethylene Glycols / chemistry
  • Polymers / administration & dosage
  • Polymers / chemistry*

Substances

  • Antineoplastic Agents, Phytogenic
  • Caproates
  • Lactones
  • Polyesters
  • Polymers
  • Polyethylene Glycols
  • poly(lactide)
  • caprolactone
  • Irinotecan
  • Camptothecin