Design and Characterization of Paclitaxel-Loaded Polymeric Nanoparticles Decorated With Trastuzumab for the Effective Treatment of Breast Cancer

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.

Development of favipiravir loaded PLGA nanoparticles entrapped in in-situ gel for treatment of Covid-19 via nasal route

“…The probable reason could be as initially the amount of poloxamer 407 could be sufficient for reduction of particle size. Nevertheless, further increase in surfactant concentration caused increase in particle size due to adsorption of poloxamer 407 on NPs surface resulted formation of thick coating [ 27 ]. Furthermore, with increase in surfactant amount viscosity of aqueous phase also rises resulting large particle size [ 28 ].…”

Efficient Synthesis with Green Chemistry Approach of Novel Pharmacophores of Imidazole-Based Hybrids for Tumor Treatment: Mechanistic Insights from In Situ to In Silico

“…The cells were seeded in a 96-well plate at a density of 1.0 × 10 4 cells/well and incubated for 24 h at 37 °C with 5% CO 2 . The medium was discarded, and both the cell lines were treated with different concentrations (25 μM, 50 μM, 75 μM, and 100 μM) of synthetic imidazole derivatives [ 32 ]. After 48 h of incubation, 20 μL of MTT solution (5 mg/mL) was pipetted into each well and incubated for another 4 h. The medium was later discarded, and the formazan precipitate was dissolved in DMSO.…”

First Report on Comparative Essential Oil Profile of Stem and Leaves of Blepharispermum hirtum Oliver and Their Antidiabetic and Anticancer Effects

“…The cells were seeded in a 96-well plate at a density of 1.0 × 10 4 cells/well and incubated for 24 h at 37 °C in 5% CO 2 . The medium was discarded, and both cell lines were treated with different concentrations (3, 10, 30, 100, and 300 μg/mL) of plant EOs [ 18 ] after 48 h of incubation (Maher et al [ 19 ]). A total of 20 μL of MTT solution (5 mg/mL) was pipetted into each well and incubated for another 4 h. The medium was later discarded, and the formazan precipitate was dissolved in DMSO.…”

“…The absorbance of the mixtures was determined using a microplate reader at 570 nm. All experiments were performed in triplicate and the cytotoxicity was expressed as a percentage of cell viability compared to the untreated control cells [ 18 ] …”