Transferrin functionalized poloxamer-chitosan nanoparticles of metformin: physicochemical characterization, in-vitro, and Ex-vivo studies

• Published in: Drug development and industrial pharmacy 2023-12, Vol.49 (12), p.734-747
• Main Authors: Birajdar, Swapnali Vasant, Mazahir, Farhan, Yadav, Awesh K
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - drug therapy; Chitosan - chemistry; Drug Carriers - chemistry; Humans; Metformin - pharmacology; Nanoparticles - chemistry; Particle Size; Poloxamer - chemistry; Transferrin
• ISSN: 0363-9045; 1520-5762
• DOI: 10.1080/03639045.2023.2282990

We report the preparation, characterization, and therapeutic evaluation of Metformin-Loaded, Transferrin-Poloxamer-Functionalized Chitosan Nanoparticles (TPMC-NPs) for their repurposing in Alzheimer's disease (AD). Usefulness of this work to establish the repurposing of metformin for the treatment of AD. The TPMC-NPs were prepared by ionic gelation method using sodium tripolyphosphate. The modification and functionalization were confirmed by FTIR and H NMR spectroscopy. The physicochemical characterization was performed using DLS, FTIR, H-NMR, CD spectroscopy, SEM, DSC, PXRD, HR-TEM, and hot-stage microscopy. The size, PDI, percent entrapment efficiency, and percent drug loading of TPMC-NPs were found to be 287.4 ± 9.5, 0.273 ± 0.067, 81.15 ± 7.17%, 11.75%±8.21%, respectively. Electron microscope analysis revealed smooth and spherical morphology. The transferrin conjugation efficiency was found to be 46% by the BCA method. loss of the secondary structure of transferrin after conjugation. PXRD data indicated the amorphous nature of the TPMC-NPs. Hot-stage microscopy and DSC confirmed the thermal stability of TPMC-NPs. The drug release showed a sustained release at pH 7.4. The DPPH assay displayed 80% antioxidant activity of TPMC-NPs in comparison with metformin and blank NPs. The cytotoxicity assay revealed 69.60% viable SH- SY5Y cells at 100 µg/mL of TPMC NPs. The nasal ciliotoxicity and mucoadhesion studies showed no significant toxicity, and 98.16% adhesion, respectively. The nasal permeability study showed the release of metformin within 30 min from TPMC-NPs. The obtained results suggested the usefulness of TPMC-NPs in the treatment of AD the intranasal route.