Encapsulation of exemestane in polycaprolactone nanoparticles: optimization, characterization, and release kinetics.

Abhinesh Kumar,Krutika Sawant

doi:10.1007/s12645-013-0037-4

Abstract

This study was aimed at developing a polymeric drug delivery system for a steroidal aromatase inhibitor, exemestane (exe) intended for sustained targeted delivery of drug through intravenous route. Carboxylated polycaprolactone (cPCL) was synthesized by ring opening polymerization of caprolactone. Exe-loaded cPCL nanoparticles (NPs) were prepared by interfacial deposition of preformed polymer and characterized. A 3-factor, 3-level Box–Behnken design was used to derive a second-order polynomial equation and construct contour and response plots for maximized response of percentage drug entrapment (PDE) with constraints on particle size (PS). The independent variables selected were ratio of exe/cPCL, amount of cPCL, and volume of organic phase. Polymerization of caprolactone to cPCL was confirmed by Fourier transform infrared (FTIR) and gel permeation chromatography. The prepared NPs were evaluated for differential scanning calorimetry (DSC), transmission electron microscopy (TEM), and in vitro release studies. Optimum formulation based on desirability (1.0) exhibited PDE of 83.96 % and PS of 180.5 nm. Check point analysis confirmed the role of the derived polynomial equation and contour plots in predicting the responses. Zeta potential of optimized formulation was −33.8 ± 2.1 mV. DSC studies confirmed the absence of any interaction between drug and polymer. TEM image showed non-aggregated and spherical shaped NPs. Drug release from NPs showed sustained release and followed Korsmeyer–Peppas model, indicating Fickian drug release. Thus, preparation of exe-loaded cPCL NPs with high PDE and desired PS suitable for providing passive targeting could be statistically optimized using Box–Behnken design.Electronic supplementary materialThe online version of this article (doi:10.1007/s12645-013-0037-4) contains supplementary material, which is available to authorized users.

Highlights

Breast cancer is the leading cause of death among women, with one million new cases in the world each year (McPherson et al 2000), out of which one third are reported to be hormone dependent (Henderson and Canellos 1980; Theobald 2000)
Successful polymerization of caprolactone to cPCL was confirmed by Fourier transform infrared (FTIR) spectra of polymer (Fig. 1)
The peak at 1,727.81 cm−1 corresponding to carboxylic group and 3,441 cm−1 for OH stretching of COOH group confirmed the conversion of caprolactone to cPCL (Zhang et al 1994)

Summary

Introduction

Breast cancer is the leading cause of death among women, with one million new cases in the world each year (McPherson et al 2000), out of which one third are reported to be hormone dependent (Henderson and Canellos 1980; Theobald 2000). Sawant for the treatment of breast cancer (Johannessen et al 1997) It acts as a false substrate for the aromatase enzyme and is processed to an intermediate that binds irreversibly to the active site of the enzyme causing its inactivation, an effect known as suicide inhibition (Dowsett 1998). The problem with the oral delivery of exe is its inability to target the tumor site. This problem can be overcome by employing delivery systems capable of providing targeted drug delivery. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are already reported to provide passive targeting of anticancer drugs to tumor site (Yallapu et al 2010; Fonseca et al 2002)

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