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Development and testing of nanoparticles delivery for P7C3 small molecule using injury models

Molecular and Cellular Biochemistry (2023)Cite this article

Abstract

The use of nanoparticles (NPs) has emerged as a potential tool for safe and effective drug delivery. In the present study, we developed small molecule P7C3-based NPs and tested its efficacy and toxicity along with the tissue specific aptamer-modified P7C3 NPs. The P7C3 NPs were prepared using poly (D, L-lactic-co-glycolic acid) carboxylic acid (PLGA-COOH) polymer, were conjugated with skeletal muscle-specific RNA aptamer (A01B P7C3 NPs) and characterized for its cytotoxicity, cellular uptake, and wound healing in vitro. The A01B P7C3 NPs demonstrated an encapsulation efficiency of 30.2 ± 2.6%, with the particle size 255.9 ± 4.3 nm, polydispersity index of 0.335 ± 0.05 and zeta potential of + 10.4 ± 1.8mV. The FTIR spectrum of P7C3 NPs displayed complete encapsulation of the drug in the NPs. The P7C3 NPs and A01B P7C3 NPs displayed sustained drug release in vitro for up to 6 days and qPCR analysis confirmed A01B aptamer binding to P7C3 NPs. The C2C12 cells viability assay displayed no cytotoxic effects of all 3 formulations at 48 and 72 h. In addition, the cellular uptake of A01B P7C3 NPs in C2C12 myoblasts demonstrated higher uptake. In vitro assay mimicking wound healing showed improved wound closure with P7C3 NPs. In addition, P7C3 NPs significantly decreased TNF-α induced NF-κB activity in the C2C12/NF-κB reporter cells after 24-hour treatment. The P7C3 NPs showed 3-4-fold higher efficacy compared to P7C3 solutions in both wound-closure and inflammation assays in C2C12 cells. Furthermore, the P7C3 NPs showed 3-4-fold higher efficacy in reducing the infarct size and protected mouse hearts from ex vivo ischemia-reperfusion injury. Overall, this study demonstrates the safe and effective delivery of P7C3 NPs.

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Acknowledgements

The authors would also like to acknowledge the Lisa Muma Weitz Laboratory for Advanced Microscopy & Cell Imaging, USF Health, University of South Florida, Tampa, FL, USA for providing facility for microscopy and imaging.

Funding

This research was funded by NIH DK119066, and Saunders Endowment to SMT.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Taneja College of Pharmacy, University of South Florida, Tampa, FL, 33612, USA

    Vijaykumar Sutariya, Aren Saini, Abraian Miller, Sachin L. Badole, Jared Tur, Mackenzie Gittinger, Joung Woul Kim, Ravikumar Manickam & Srinivas M. Tipparaju

  2. Department of Pharmaceutical Sciences, Wegmans School of Pharmacy, St. John Fisher University, Rochester, NY, 14618, USA

    Priyanka Bhatt

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  1. Vijaykumar Sutariya
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  2. Priyanka Bhatt
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Contributions

Conceptualization, SMT and VBS; methodology, PB, RM, ASS, AM, MG, and JWK; validation, PB, RM, and JWK; formal analysis, PB, RM, ASS, AM, MG, and JWK; resources, SMT and VBS; data curation, VBS, PB, ASS, SMT; writing—original draft preparation, PB and RM; review and editing, RM, SMT, and VBS; supervision, SMT and VBS; project administration, SMT and VBS; funding acquisition, SMT. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Srinivas M. Tipparaju.

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The authors declare no competing interests.

Patents

US Patent: Patent No.: US 11,007,178 B2 [44]. USF ref. 22A105, 19A039, 24T028. USF Disclosure for aptamer P7C3.

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Sutariya, V., Bhatt, P., Saini, A. et al. Development and testing of nanoparticles delivery for P7C3 small molecule using injury models. Mol Cell Biochem (2023). https://doi.org/10.1007/s11010-023-04865-2

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