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Preparation and Characterization of Lipophilic Doxorubicin Pro-drug Micelles

Preparation and Characterization of Lipophilic Doxorubicin Pro-drug Micelles

Published on: August 2, 2016

A biodegradable pH-sensitive micelle system for targeting acidic solid tumors.

Vijay A Sethuraman¹, Myung Cheon Lee, You Han Bae

¹Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 421 Wakara Way, Suite 318, Salt Lake City, Utah 84108, USA.

Pharmaceutical Research

|November 14, 2007

Summary

This study introduces a pH-sensitive micelle delivery system using TAT cell penetrating peptide and a biodegradable polymer. The system effectively delivers anticancer drugs, showing distinct cytotoxicity at tumor-relevant pH levels.

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Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles

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Published on: August 28, 2015

Area of Science:

Biomaterials Science
Drug Delivery Systems
Nanotechnology

Background:

Developing targeted drug delivery systems is crucial for improving cancer therapy efficacy and reducing side effects.
pH-sensitive materials offer potential for triggered drug release in tumor microenvironments.
Polymeric micelles provide a versatile platform for encapsulating and delivering therapeutic agents.

Purpose of the Study:

To develop and characterize a novel pH-sensitive micelle delivery system.
To evaluate the pH-dependent complexation, drug release, and cellular uptake of the system.
To assess the in vitro cytotoxicity of the drug-loaded system at different pH values.

Main Methods:

Synthesis of Poly(L-lactic acid)-b-poly(ethylene glycol) (PLLA-b-PEG) conjugated to TAT (TAT-micelle).
Preparation of a pH-sensitive diblock copolymer (poly(L-cystine bisamide-g-sulfadiazine))-b-PEG (PCBS-b-PEG).
Characterization of micelle complexation, particle size changes at varying pH, flow cytometry for cellular uptake, and in vitro cytotoxicity assays with doxorubicin (DOX).

Main Results:

The TAT-micelle and PCBS-b-PEG formed a pH-sensitive carrier, with observable complexation and particle size changes between pH 8.0 and 7.0.
At lower pH (6.8-6.0), two populations of micelles and aggregates were observed, indicating pH-triggered dissociation.
Flow cytometry demonstrated significantly higher cellular uptake at pH 6.6 compared to pH 7.4, suggesting effective deshielding.
The doxorubicin-loaded system exhibited distinct in vitro cytotoxicity at pH 7.2 versus pH 7.0, highlighting pH-sensitivity.

Conclusions:

The developed pH-sensitive micelle system effectively complexes and dissociates in response to pH changes.
The system shows enhanced cellular uptake at acidic pH, characteristic of tumor microenvironments.
This pH-sensitive delivery system demonstrates potential for targeted anticancer drug delivery, distinguishing between physiological and tumor-associated pH levels.