Design, Development, Characterization and Evaluation of Docetaxel- Loaded Microspheres to Treat Breast Cancer: In Vitro and in Vivo Evaluation

The aim of this study was to prepare docetaxel-loaded synthetic (Gelatin and PLGA) and natural polymers (coffee bean extract and Ganoderma) microspheres and to evaluate their in vitro and in vivo characteristics. In which the optimized formulation has been described below. 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 advantages 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 (115 ± 5 nm); the encapsulation efficiency and drug loading of prepared microspheres were 93 ± 2 and 8.7% ± 0.2%, 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 (mammary gland). The optimized formulation could be effectively internalized into metastatic 4T1 breast cancer cells in vitro. 10 µg/mL or an equivalent concentration of the formulation did not significantly affected the viability of 4T1 cells, but dramatically decreased the cell migration activities. In metastatic breast cancer model, intravenously administered optimized formulation could be efficiently delivered to the tumor sites, resulting in a 96.3% inhibition of tumor growth with 3.77% of cell death and a 93.5% reduction of lung metastases. 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.