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In Vivo Cancer Microenvironment Responsive Glycan Receptor-Targeted Nanoparticles for Gemcitabine Delivery to Benzo[a]pyrene-Induced Lung Cancer Model

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Abstract

Targeted gemcitabine (GEB) loaded 5-N-acetyl-neuraminic acid (Neu5Ac) assembled chitosan nanoparticles (CA-NPs) were formulated by ionotropic gelation process and evaluated for physicochemical and morphological characterization, in vitro and in vivo studies in A-549 cells and lung cancer mice model, respectively. The mean diameter of GEB-CA-Neu5Ac-NPs determined by dynamic light scattering was 161.16 ± 7.70 nm with a polydispersity index (PDI) value of 0.303 ± 0.011 and its zeta potential and entrapment efficiency (%EE) were 40.3 ± 3.45 mv and 66.11 ± 1.94%, respectively. The in vitro cellular uptake studies showed that glycan receptor-targeted nanoparticles deliver significantly more amount (p < 0.001) of GEB into the A-549 lung cancerous cells than non-targeted nanoparticles. The cytotoxicity study using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay clearly demonstrated that GEB-CA-Neu5Ac-NPs have lower IC50 value (6.39 ± 3.78 µg/ml) than others groups that showed that the greater lung cancerous cells inhibition potential of targeted nanoparticles. The in vivo biodistribution of the GEB-loaded 5-N-acetyl-neuraminic acid conjugated chitosan nanoparticles was revealed that targeted nanoparticles showed higher accumulation and retention for an extended period of time due to the active targeting ability of Neu5Ac to glycan receptors. Histopathological examination showed significant recovery in the physiological architecture upon administration of targeted nanoparticles. The glycan receptor-targeted nanoparticles treated groups showed a significant decline in the number of metastatic lung epithelial cells, as compared to the untreated positive control group (p < 0.001) confirming higher anticancer efficacy of the GEB-CA-Neu5Ac-NPs.

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Acknowledgements

The authors express their gratitude to the Ministry of Human Resource and Development (MHRD)-India for providing a Teaching Assistantship. Furthermore, the authors would like to acknowledge CIF-IIT BHU for their assistance in conducting the instrumental characterization of formulations.

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Authors and Affiliations

  1. Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, U.P., India

    Krishan Kumar,  Manjit, Mohini Mishra, Varsha Rani & Ruchi Chawla

  2. School of Biomedical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi, 221005, U.P., India

    Rinki Verma

  3. Department of Pharmacy, Barkatullah University, Bhopal, 462026, M.P., India

    Priya

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  1. Krishan Kumar
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Contributions

Krishan Kumar: conceptualization, project administration, writing — original draft, review, and editing, methodology, formal analysis, resources, investigation, software; Rinki Verma: resources; Manjit: resources, validation, data curation; Priya: writing — review and editing; Mohini Mishra: visualization; Varsha Rani: data curation; Ruchi Chawla: supervision, visualization, writing — review and editing.

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Kumar, K., Verma, R., Manjit et al. In Vivo Cancer Microenvironment Responsive Glycan Receptor-Targeted Nanoparticles for Gemcitabine Delivery to Benzo[a]pyrene-Induced Lung Cancer Model. AAPS PharmSciTech 25, 2 (2024). https://doi.org/10.1208/s12249-023-02714-5

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