Cyclodextrin-derived pH-responsive nanoparticles for delivery of paclitaxel

Biomaterials. 2013 Jul;34(21):5344-58. doi: 10.1016/j.biomaterials.2013.03.068. Epub 2013 Apr 13.

Abstract

Engineering of pH-responsive nanoplatforms can be facilely achieved from acetalated α-cyclodextrin materials. The hydrolysis period of nanoparticles can be precisely tailored by using materials with various acetal types that can be easily controlled by acetalation time. These nanomaterials with pH-modulated hydrolysis and pH-triggered drug delivery capability show good biocompatibility in vitro and in vivo. Incorporation of anticancer drug paclitaxel (PTX) into newly developed pH-sensitive nanosystems leads to nanotherapeutics with significantly improved cytotoxic activity against various tumor cells. Importantly, thus formulated nanomedicines can reverse the multidrug resistance of PTX-resistant cancer cells. In vivo antitumor studies also reveal the superior of pH-sensitive nanosystems over pristine PTX and pH-insensitive PLGA nanoformulations. Moreover, comparison with other two acid-labile materials evidenced the advantages of cyclodextrin-based nanovehicles with respect to drug loading capacity, in vitro and in vivo activity as well as alleviated adverse effects. These pH-responsive nanoparticles may serve as new generation nanocarriers for drug delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Animals
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods*
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Humans
  • Hydrogen-Ion Concentration / drug effects
  • Intracellular Space / drug effects
  • Intracellular Space / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity
  • Nanoparticles / ultrastructure
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Paclitaxel / pharmacology*
  • Toxicity Tests, Acute
  • Xenograft Model Antitumor Assays
  • alpha-Cyclodextrins / chemistry*

Substances

  • Drug Carriers
  • alpha-Cyclodextrins
  • Paclitaxel
  • alpha-cyclodextrin