Development of paclitaxel loaded pegylated gelatin targeted nanoparticles for improved treatment efficacy in non-small cell lung cancer (NSCLC): an in vitro and in vivo evaluation study
Purpose: To develop and evaluate paclitaxel (PTX) loaded pegylated gelatin targeted nanoparticles for improved efficacy in non-small cell lung cancer (NSCLC) treatment. Method: PTX loaded gelatin nanoparticles (PTX-GNP) were prepared by crosslinking with glutaraldehyde aqueous solution. These nanoparticles (NPs) were further incubated with PEG 400 to form PEGylated NPs (PEG-PTX-GNP). The NPs were evaluated for surface morphology, size, zeta potential, encapsulation efficiency, drug loading, in vitro drug release, cytotoxicity in an assay on cancer cell lines L132, in vitro cellular uptake in an assay in L132 and 293T cell lines, in vivo antitumor activity on female Balb/c mice, pulmonary deposition, histopathology, and immunohistochemical properties. Results: The nanoparticles were of spherical shape with smooth surface characteristics. The observed DL was of 20.18 to 32.11%, as particle size was of 90 to 115 nm. Zeta potential and polydispersity index (PDI) were within acceptable ranges. Encapsulation was effective when the NPs had a size of 80.50 nm to 98.12 nm. The PEGylated PTX loaded nanoparticles (PEG-PTX-GNP, GNP4) showed similar PTX release profile to that of the NP4 formulation. PEGylated NPs showed the desired PTX release pattern that is required for cancer treatment. In an in vitro cytotoxicity study, PEG-PTX-GNP showed the maximum antiproliferative activity over the period of 24 hours, followed by PTX-GNP, pure PTX and BPEG-GNP. PEG-PTX-GNP showed the highest internalization within both cell lines, followed by PTX-GNP and pure PTX. The survival rate of animals in PEG-PTX-GNP group was 100%, proving the safety and efficacy of the treatment. PEG-PTX-GNP showed the highest antitumor activity as compared to other formulations. The pulmonary deposition rate was the highest (6.5 to 12.55 μg/g) in PEG-PTX-GNP formulations. Histopathology and immunohistochemical study proved that PEG-PTX-GNP had greater anticancer potential than other tested formulations. Conclusion: This study confirms the potential use of paclitaxel loaded PEGylated gelatin targeted nanoparticles for improved efficacy in non-small cell lung cancer (NSCLC) treatment.
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