Docetaxel-Loaded Chitosan Microspheres as a Lung Targeted Drug Delivery System: In Vitro and in Vivo Evaluation

Hao Wang,Yongdong Xu,Xiao Zhou

doi:10.3390/ijms15033519

Abstract

The aim of this study was to prepare docetaxel-loaded chitosan microspheres and to evaluate their in vitro and in vivo characteristics. Glutaraldehyde crosslinked microspheres were prepared using a water-in-oil emulsification method, and characterized in terms of the morphological examination, particle size distribution, encapsulation ratio, drug-loading coefficient and in vitro release. Pharmacokinetics and biodistribution studies were used to evaluate that microspheres have more advantage than the conventional formulations. The emulsion crosslinking method was simple to prepare microspheres and easy to scale up. The formed microspheres were spherical in shape, with a smooth surface and the size was uniform (9.6 ± 0.8 μm); the encapsulation efficiency and drug loading of prepared microspheres were 88.1% ± 3.5% and 18.7% ± 1.2%, respectively. In vitro release indicated that the DTX microspheres had a well-sustained release efficacy and in vivo studies showed that the microspheres were found to release the drug to a maximum extent in the target tissue (lung). The prepared microspheres were found to possess suitable physico-chemical properties and the particle size range. The sustained release of DTX from microspheres revealed its applicability as drug delivery system to minimize the exposure of healthy tissues while increasing the accumulation of therapeutic drug in target sites.

Highlights

Docetaxel (Taxotere®) (DTX, Figure 1) is a second-generation taxane derived from the needles of the European yew tree, Taxus baccata [1], which comprises the most commonly used chemotherapeutic agents for treating solid tumors, especially lung cancer [2,3]
Previous reports have shown that several methods have been used for preparing loaded chitosan microspheres, such as interaction with the anions method [18], the emulsion crosslinking method [19], the precipitation or coacervation method [20], the solvent evaporation method [21], and the spray drying method [22]
Glutaraldehyde was used as crosslinking agents for the preparation of microspheres

Summary

Introduction

Docetaxel (Taxotere®) (DTX, Figure 1) is a second-generation taxane derived from the needles of the European yew tree, Taxus baccata [1], which comprises the most commonly used chemotherapeutic agents for treating solid tumors, especially lung cancer [2,3]. DTX acts by disrupting the microtubular network that is essential for mitotic and interphase cellular functions. It promotes the assembly of tubulin into stable microtubules and inhibits their disassembly, causing inhibition of cell division and eventual cell death. The efficacy of DTX is frequently limited by their inability to reach the target site of action, especially when

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Methods

Results