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Subcutaneous Delivery of Albumin: Impact of Thermosensitive Hydrogels

  • Research Article
  • Theme: NIPTE Research and Perspective: Advances in Nanotechnology-Based Drug Delivery
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Abstract

Albumin demonstrates remarkable promises as a versatile carrier for therapeutic and diagnostic agents. However, noninvasive delivery of albumin-based therapeutics has been largely unexplored. In this study, injectable thermosensitive hydrogels were evaluated as sustained delivery systems for Cy5.5-labeled bovine serum albumin (BSA-Cy5.5). These hydrogels were prepared using aqueous solutions of Poloxamer 407 (P407) or poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PLGA-PEG-PLGA), which could undergo temperature-triggered phase transition and spontaneously solidify into hydrogels near body temperature, serving as in situ depot for tunable cargo release. In vitro, these hydrogels were found to release BSA-Cy5.5 in a sustained manner with the release half-life of BSA-Cy5.5 from P407 and PLGA-PEG-PLGA hydrogels at 16 h and 105 h, respectively. Without affecting the bioavailability, subcutaneous administration of BSA-Cy5.5-laden P407 hydrogel resulted in delayed BSA-Cy5.5 absorption, which reached the maximum plasma level (Tmax) at 24 h, whereas the Tmax for subcutaneously administered free BSA-Cy5.5 solution was 8 h. Unexpectedly, subcutaneously injected BSA-Cy5.5-laden PLGA-PEG-PLGA hydrogel did not yield sustained BSA-Cy5.5 plasma level, the bioavailability of which was significantly lower than that of P407 hydrogel (p < 0.05). The near-infrared imaging of BSA-Cy5.5-treated mice revealed that a notable portion of BSA-Cy5.5 remained trapped within the subcutaneous tissues after 6 days following the subcutaneous administration of free solution or hydrogels, suggesting the discontinuation of BSA-Cy5.5 absorption irrespective of the formulations. These results suggest the opportunities of developing injectable thermoresponsive hydrogel formulations for subcutaneous delivery of albumin-based therapeutics.

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Author notes

  1. Nidhi Patel and Nan Ji contributed equally to the work.

Authors and Affiliations

  1. Department of Pharmaceutics and Drug Delivery, University of Mississippi School of Pharmacy, University, Mississippi, USA

    Nidhi Patel, Nan Ji, Yingzhe Wang & Chalet Tan

  2. National Center for Natural Products Research, University of Mississippi School of Pharmacy, University, Mississippi, USA

    Xingcong Li

  3. Pharma Solutions, BASF Corporation, Florham Park, New Jersey, USA

    Nigel Langley

Authors
  1. Nidhi Patel
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  2. Nan Ji
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  3. Yingzhe Wang
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  4. Xingcong Li
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  5. Nigel Langley
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  6. Chalet Tan
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Correspondence to Chalet Tan.

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Guest Editors: Xiuling Lu and Aliasger K Salem

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Patel, N., Ji, N., Wang, Y. et al. Subcutaneous Delivery of Albumin: Impact of Thermosensitive Hydrogels. AAPS PharmSciTech 22, 120 (2021). https://doi.org/10.1208/s12249-021-01982-3

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  • DOI: https://doi.org/10.1208/s12249-021-01982-3

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