Abstract
The aim of the study was to design and formulate an antibody-mediated targeted, biodegradable polymeric drug delivery system releasing drug in a controlled manner to achieve a therapeutic goal for the effective treatment of breast cancer. Antibody-mediated paclitaxel-loaded PLGA polymeric nanoformulations were prepared by the solvent evaporation method using different experimental parameters and compatibility studies. The optimized formulations were selected for in vitro and in vivo evaluation and cytotoxicity studies. The in vitro drug release studies show a biphasic release pattern for the paclitaxel-loaded PLGA nanoparticles showing a burst release for 24 h followed by an extended release for 14 days; however, a more controlled and sustained release was observed for antibody-conjugated polymeric nanoparticles. The cytotoxicity of reference drug and paclitaxel-loaded PLGA nanoparticles with and without antibody was determined by performing MTT assay against MCF-7 cells. Rabbits were used as experimental animals for the assessment of various in vivo pharmacokinetic parameters of selected formulations. The pharmacokinetic parameters such as Cmax (1.18–1.33 folds), AUC0-t (39.38–46.55 folds), MRT (10.04–12.79 folds), t1/2 (3.06–4.6 folds), and Vd (6.96–8.38 folds) have been increased significantly while clearance (4.34–4.61 folds) has been decreased significantly for the selected nanoformulations as compared to commercially available paclitaxel formulation (Paclixil®). The surface conjugation of nanoparticles with trastuzumab resulted in an increase in in vitro cytotoxicity as compared to plain nanoformulations and commercially available conventional brand (Paclixil®). The developed PLGA-paclitaxel nanoformulations conjugated with trastuzumab have the desired physiochemical characteristics, surface morphology, sustained release kinetics, and enhanced targeting.
Highlights
Cancer is a disease in which genes regulating the functions of cells, i.e., cell growth, division, differentiation, and cell death losses are without any control (Liotta et al, 1991)
Sustained release of paclitaxel-loaded polymeric nanoparticles decorated with trastuzumab was developed using poly lactic co glycolic acid (PLGA), sodium lauryl sulfate (SLS), and poloxamer 407 by the solvent evaporation method
The formulations were evaluated for its in vitro cellular cytotoxicity against HER2+ breast cancer cell lines
Summary
Cancer is a disease in which genes regulating the functions of cells, i.e., cell growth, division, differentiation, and cell death losses are without any control (Liotta et al, 1991). Breast cancer receptors are divided into two main types, i.e., estrogen receptor (ER) negative and human epidermal growth factor receptors (HER2) positive (Carey et al, 2006). Breast cancer is treated nowadays by different ways, i.e., hormone-blocking agents, chemotherapy, radiotherapy, monoclonal antibodies, and surgery (Waks & Winer, 2019). Main problems with concventional drug delivery systems are fluctuations of drug concentrations in blood which in turn causes subtherapeutic concentration or toxic effects. Multidrug resistance, toxicity of chemotherapeutic agents, side effects, limited aqueous solubility, and poor bioavailability are some of the limitations with available cancer therapy (Chidambaram et al, 2011). The major target of any drug delivery system and controlled drug delivery system is to make the therapeutically effective amount of drug available at a desired site, at an optimum concentration, and for a desired period of time (Win, 2006)
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