Dexamethasone-Loaded Poly(Lactic-Co-Glycolic) Acid Microspheres/Poly(Vinyl Alcohol) Hydrogel Composite Coatings for Inflammation Control

Patil, Siddhesh D.; Papadimitrakopoulos, Fotios; Burgess, Diane J.

doi:10.1089/dia.2004.6.887

Cited by 121 publications

(94 citation statements)

References 32 publications

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“…27 Some studies have proposed coating implantable medical devices with anti inflammatory drug releasing systems. 25,28 However to ensure that the implanted drug delivery device lasts for a long duration, a different approach to locally affect tissue responses is urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Species and Density of Implant Surface Chemistry Affect the Extent of Foreign Body Reactions

et al. 2008

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Implant-associated fibrotic capsule formation presents a major challenge for the development of long term drug release microspheres and implantable sensors. Since material properties have been shown to affect in vitro cellular responses and also to influence short term in vivo tissue responses, we have thus assumed that the type and density of surface chemical groups would affect the degree of tissue responses to microsphere implants. To test this hypothesis, polypropylene particles with different surface densities of -OH and -COOH groups, along with the polypropylene control (-CH 2 groups) were utilized. The influence of functional groups and their surface densities on tissue reactions were analyzed using a mice subcutaneous implantation model. Our comparative studies included determination and correlation of the extents of fibrotic capsule formation, cell infiltration into the particles and recruitment of CD11b+ inflammatory cells for all of the substrates employed. We have observed major differences among microspheres coated with different surface functionalities. Surfaces with -OH surface groups trigger the strongest responses while -COOH rich surfaces prompt the least tissue reactions. However, variation of the surface density of either functional group has a relatively minor influence on the extent of fibrotic tissue reactions. The present results show that surface functionality can be used as a powerful tool to alter implant-associated fibrotic reactions and, potentially, to improve the efficacy and function of drug delivery microspheres, implantable sensors and tissue engineering scaffolds.

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Section: Introductionmentioning

confidence: 99%

Species and Density of Implant Surface Chemistry Affect the Extent of Foreign Body Reactions

et al. 2008

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“…The most commonly used drug has been dexamethasone which modulates macrophage behaviour and reduces the levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF)- (Joyce et al, 1997;Umland et al, 2002). Burgess and co-workers embedded dexamethasone-containing PLGA microspheres in PVA hydrogels to create a 'smart' coating for glucose sensors which allowed rapid diffusion of analytes and slow release of dexamethasone (Hickey et al, 2002;Patil et al, 2004). Other anti-inflammatory strategies investigated include heparin-based coatings to reduce protein adsorption and leukocyte recruitment (Rele et al, 2005) and covalent conjugation of a superoxide dismutase mimetic to the surface of biomaterials, resulting in reduced neutrophil recruitment and inhibition of foreign body giant cell and fibrous tissue capsule formation (Udipi et al, 2000).…”

Section: Modification Of the Foreign Body Responsementioning

confidence: 99%

The Fibrotic Response to Implanted Biomaterials: Implications for Tissue Engineering

Rolfe¹,

Mooney²,

Zhang³

et al. 2011

Regenerative Medicine and Tissue Engineering - Cells and Biomaterials

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“…The rationale for the use of HAs in these composites has been discussed previously. 10,13 In vivo pharmacodynamic study All animal studies were conducted at the University of Connecticut in accordance with Institutional Animal Care and Use Committee (IACUC) guidelines using an approved protocol (#A05-015). All procedures were performed as discussed previously.…”

Section: Preparation Of Compositesmentioning

confidence: 99%

“…The fast release of dexamethasone from these composites effectively prevented the acute inflammatory response up to day 8. The amount of dexamethasone used to prepare the fast releasing microspheres was the same as that used in the previous study 10 but the release rates were different. The release was over a one month period in the previous study.…”

Section: Preparation Of Compositesmentioning

confidence: 99%

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

Bhardwaj

Sura

Papadimitrakopoulos

et al. 2007

J Diabetes Sci Technol

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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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Dexamethasone-Loaded Poly(Lactic-Co-Glycolic) Acid Microspheres/Poly(Vinyl Alcohol) Hydrogel Composite Coatings for Inflammation Control

Cited by 121 publications

References 32 publications

Species and Density of Implant Surface Chemistry Affect the Extent of Foreign Body Reactions

Species and Density of Implant Surface Chemistry Affect the Extent of Foreign Body Reactions

The Fibrotic Response to Implanted Biomaterials: Implications for Tissue Engineering

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

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