Cited by 99Hydrogels: synthesis, properties, applicationsAdvanced Drug Delivery SystemsWound Healing and Treatments

Controlling Acute Inflammation with Fast Releasing Dexamethasone-PLGA Microsphere/PVA Hydrogel Composites for Implantable Devices

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Bhardwaj, Upkar, Sura, Radhakrishna, Papadimitrakopoulos, Fotios, Burgess, Diane J.·2007·Journal of Diabetes Science and Technology

Abstract

Background: Continuous release of dexamethasone from PLGA microsphere/PVA hydrogel composites has been shown to suppress the inflammatory tissue reaction in response to subcutaneously implanted foreign material for a period of one month. The scope of the present work is to investigate whether suppressing the initial acute inflammatory phase with fast releasing dexamethasone-PLGA microsphere/PVA composites (that release the drug over a period of one week) would prevent the development of a foreign body reaction in response to implantation in the subcutaneous tissue using a rat model. Methods: Dexamethasone loaded PLGA microspheres were prepared using the solvent evaporation method. In vitro release from microspheres was analyzed using USP apparatus 4 in phosphate buffered saline (PBS) at 37°C. Composites were fabricated in 18G needles by freeze-thaw cycling the PVA/microsphere dispersion. The composites were implanted in the subcutaneous tissue of anesthetized rats. The pharmacodynamic effect was evaluated by histological examination of the tissue surrounding the composites at pre-determined time points. Results: In vitro release studies showed that most of the drug entrapped in the microspheres was released within one week. At days 3 and 8, these fast releasing dexamethasone containing composites suppressed the acute phase of inflammation but did not prevent the development of an inflammatory reaction after dexamethasone was completely released from the composites. By day 30, chronic inflammation and fibrosis were observed in the tissue surrounding the drug-containing composites. On days 3 and 8, the number of inflammatory cells in the vicinity of the dexamethasone containing composites was similar to that in normal tissue. However, the number of inflammatory cells was higher in drug-containing composites as compared to drug-free composites by day 30. This was due to the inflammation being in a more advanced stage in drug-free composites where a granulomatous reaction had already developed. Conclusion: Fast release of dexamethasone from PLGA/PVA composites did not provide long-term protection against the foreign body reaction in response to implantation. It would appear that a sustained delivery of anti-inflammatory agents such as dexamethasone is necessary to suppress inflammation throughout the implant life-time.

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Registry

Crossref · 10.1177/193229680700100103

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  • Short dexamethasone delivery diminished acute inflammation at 3 and 8 days but inflammation significantly increased at 30 days, indicating that dexamethasone release delayed the immune response.

    “The acute inflammatory response was diminished at 3 and 8 d, but inflammation was significantly increased at 30 d compared to the shorter time points (i.e., 3 and 8 d), indicating that DX release simply delayed the immune response.186”

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Authors
Bhardwaj, U., Sura, R., Papadimitrakopoulos, F., & Burgess, D. J.
Affiliations
University of Connecticut (US)
Corresponding author
Burgess, Diane J.
Venue
Journal of Diabetes Science and Technology
Published
2007-01
Volume
1
Issue
1
Pages
8-17
ISSN
1932-2968 (ISSN-L)
OpenAlex
W2127553413
Cited by
99
References
16
Citations by year
2026: 3 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 16 · 2014: 6 · 2013: 11 · 2012: 8
FWCI
2.78
Type
journal article
Language
en
Open access
Locations
  • Journal of Diabetes Science and Technology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
Keywords
dexamethasone, PLGA microspheres, polyvinyl alcohol hydrogel, foreign body reaction, acute inflammation, biomedical implants, sustained drug release, granulomatous inflammation, subcutaneous implantation, anti-inflammatory drug delivery

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