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

Deepa A. Rao; Duc X. Nguyen; Gyan P. Mishra; Bhuvana Shyam Doddapaneni; Adam W. G. Alani

doi:10.3791/53047

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Method Article

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

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DOI:

10.3791/53047

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August 28th, 2015

Deepa A. Rao¹ , Duc X. Nguyen² , Gyan P. Mishra² , Bhuvana Shyam Doddapaneni² , Adam W. G. Alani²

¹School of Pharmacy, Pacific University, ²Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University

Summary

The goal of this protocol is to describe the preparation and characterization of physically entrapped, poorly water soluble drugs in micellar drug delivery systems composed of amphiphilic block copolymers.

Abstract

Amphiphilic block copolymers like polyethyleneglycol-block-polylactic acid (PEG-b-PLA) can self-assemble into micelles above their critical micellar concentration forming hydrophobic cores surrounded by hydrophilic shells in aqueous environments. The core of these micelles can be utilized to load hydrophobic, poorly water soluble drugs like docetaxel (DTX) and everolimus (EVR). Systematic characterization of the micelle structure and drug loading capabilities are important before in vitro and in vivo studies can be conducted. The goal of the protocol described herein is to provide the necessary characterization steps to achieve standardized micellar products. DTX and EVR have intrinsic solubilities of 1.9 and 9.6 µg/ml respectively Preparation of these micelles can be achieved through solvent casting which increases the aqueous solubility of DTX and EVR to 1.86 and 1.85 mg/ml, respectively. Drug stability in micelles evaluated at room temperature over 48 hr indicates that 97% or more of the drugs are retained in solution. Micelle size was assessed using dynamic light scattering and indicated that the size of these micelles was below 50 nm and depended on the molecular weight of the polymer. Drug release from the micelles was assessed using dialysis under sink conditions at pH 7.4 at 37 ^oC over 48 hr. Curve fitting results indicate that drug release is driven by a first order process indicating that it is diffusion driven.

Introduction

Amphiphilic block copolymers with repeating structure composed of hydrophilic and hydrophobic domains can spontaneously self-assemble to form three dimensional macromolecular assemblies known as polymeric micelles. These structures have an inner hydrophobic core surrounded by a hydrophilic shell. The hydrophobic core has the ability to incorporate hydrophobic drugs either by physical entrapment through hydrophobic interactions or by chemical conjugation on to the polymer backbone.¹ Many advantages exist to using these block copolymers to form micelles for drug delivery. These include incorporation of poorly soluble drugs, improving pharmacokinetics of the i....