Dexamethasone-Loaded Poly(Lactic-Co-Glycolic) Acid Microspheres/Poly(Vinyl Alcohol) Hydrogel Composite Coatings for Inflammation Control
Abstract
BACKGROUND: Successful performance of implantable glucose biosensors for metabolic monitoring is dependent on tissue compatibility. Negative immunostimulatory tissue reactions that occur due to implantation-induced tissue injury and the prolonged presence of such sensors can lead to a loss of functionality and device failure. The use of novel poly(lactic-co-glycolic) acid (PLGA) microsphere/poly(vinyl alcohol) (PVA) hydrogel composite coatings for implantable biosensors to control localized inflammation and fibrosis at the sensor/tissue interface is reported. METHODS: Dexamethasone-loaded PLGA microspheres were prepared using a solvent evaporation technique. Composites were fabricated by dispersing microspheres in PVA solution and performing freeze-thaw cycling. Composites were implanted into subcutaneous tissue of rats. In vitro and in vivo drug release kinetics were studied. Immunostimulatory response was determined through histopathological evaluation of excised tissue. RESULTS: PLGA microsphere/PVA hydrogel composites achieved localized dexamethasone delivery with approximate zero-order release kinetics. A linear level A in vitro-in vivo correlation was observed (R2 = 0.97). Dexamethasone released at a steady rate of 0.17 microg/day was sufficient to control acute and chronic inflammation as well as fibrosis. Implantation of composites containing no drug led to significant infiltration of inflammation-mediating cells at the implant site characteristic of acute inflammation followed by proliferation of a fibrotic band surrounding the implant by week 3. CONCLUSIONS: PLGA microsphere/PVA hydrogel composites eluting dexamethasone were successful in controlling negative tissue reactions at the sensor-tissue interface by reducing the level of inflammation-mediation cells to those observed in normal tissue. These composites show promise as coatings for implantable biosensors to improve biocompatibility and prolong sensor lifetime.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Dexamethasone-releasing composites still exhibited reduced inflammation and fibrosis compared to control hydrogels at about 3 weeks, demonstrating that local dexamethasone release can arrest fibrous encapsulation.
“As chronic inflammation set in at ~3 weeks, the DX-releasing composites still exhibited reduced inflammation and fibrosis compared to control hydrogels, demonstrating the ability of local DX release to arrest fibrous encapsulation.188”
From Biocompatible Materials for Continuous Glucose Monitoring Devices (2013) · cites this paper as [188]
Dexamethasone release reduced the inflammatory response by about 50% at 3 and 7 days compared to control PLGA/PVA hydrogel composites.
“The release of DX reduced the inflammatory response by ~50% at 3 and 7 d compared to control PLGA/PVA hydrogel composites.188”
From Biocompatible Materials for Continuous Glucose Monitoring Devices (2013) · cites this paper as [188]
Cites
Glucose Biosensors: 40 Years of Advances and Challenges
Wang, J. (2001) · Electroanalysis · doi:10.1002/1521-4109(200108)13:12 · Cited by 765 · see citing works
Degradation of poly(lactic-co-glycolic acid) microspheres: Effect of copolymer composition
Park, T. G. (1995) · Biomaterials · doi:10.1016/0142-9612(95)93575-x · Cited by 642 · see citing works
Liu, S., & Ju, H. (2003) · Biosensors and Bioelectronics · doi:10.1016/s0956-5663(03)00172-6 · Cited by 471 · see citing works
Characterization of implantable biosensor membrane biofouling
Wisniewski, N. A., Moussy, F. G., & Reichert, W. M. (2000) · Fresenius Journal of Analytical Chemistry · doi:10.1007/s002160051556 · Cited by 351 · see citing works
Sensors for glucose monitoring: technical and clinical aspects
Koschinsky, T., & Heinemann, L. (2001) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.188 · Cited by 288 · see citing works
Fisher, J. P., Vehof, J. W. M., Dean, D., van der Waerden, J. P. C. M., Holland, T. A., Mikos, A. G., & Jansen, J. A. (2001) · Journal of Biomedical Materials Research · doi:10.1002/jbm.1268 · Cited by 253 · see citing works
Hickey, T., Kreutzer, D. L., Burgess, D. J., & Moussy, F. G. (2002) · Journal of Biomedical Materials Research · doi:10.1002/jbm.10016 · Cited by 187 · see citing works
Self-citationBurczak, K., Gamian, E., & Kochman, A. (1996) · Biomaterials · doi:10.1016/s0142-9612(96)00076-2 · Cited by 147 · see citing works
Bourke, S. L., Al-Khalili, M., Briggs, T., et al. (2003) · AAPS PharmSci · doi:10.1208/ps050433 · Cited by 127 · see citing works
Prolonged duration local anesthesia from tetrodotoxin-enhanced local anesthetic microspheres
Kohane, D. S., Smith, S. E., Louis, D. N., et al. (2003) · Pain · doi:10.1016/s0304-3959(03)00049-6 · Cited by 123 · see citing works
Performance of subcutaneously implanted glucose sensors for continuous monitoring
Gerritsen, M. (1999) · The Netherlands Journal of Medicine · doi:10.1016/s0300-2977(99)00006-6 · Cited by 122 · see citing works
Schliecker, G., Schmidt, C., Fuchs, S., Ehinger, A. M., Sandow, J., & Kissel, T. (2003) · Journal of Controlled Release · doi:10.1016/j.jconrel.2003.09.003 · Cited by 98 · see citing works
In vivo biocompatibility of gelatin-based hydrogels and interpenetrating networks
Stevens, K. R., Einerson, N. J., Burmania, J. A., & Kao, W. J. (2002) · Journal of Biomaterials Science Polymer Edition · doi:10.1163/15685620260449741 · Cited by 96 · see citing works
Properties of a heparin‐poly(vinyl alcohol) hydrogel coating
Goosen, M. F. A., & Sefton, M. V. (1983) · Journal of Biomedical Materials Research · doi:10.1002/jbm.820170212 · Cited by 94 · see citing works
Biosensors for in vivo glucose measurement: can we cross the experimental stage
Abel, P., & von Woedtke, T. (2002) · Biosensors and Bioelectronics · doi:10.1016/s0956-5663(02)00099-4 · Cited by 90 · see citing works
Kim, T.-K., & Burgess, D. J. (2002) · Journal of Pharmacy and Pharmacology · doi:10.1211/002235702760089009 · Cited by 79 · see citing works
Self-citationFournier, E., Passirani, C., Colin, N., et al. (2003) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/s0939-6411(03)00146-2 · Cited by 78 · see citing works
Galeska, I., Hickey, T., Moussy, F. G., Kreutzer, D. L., & Papadimitrakopoulos, F. (2001) · Biomacromolecules · doi:10.1021/bm010112y · Cited by 62 · see citing works
Self-citationA novelin vitro release technique for peptide-containing biodegradable microspheres
Kostanski, J. W., & DeLuca, P. P. (2000) · AAPS PharmSciTech · doi:10.1208/pt010104 · Cited by 61 · see citing works
Biocompatibility and degradation of poly(ether–ester) microspheres: in vitro and in vivo evaluation
van Dijkhuizen-Radersma, R., Hesseling, S. C., Kaim, P., de Groot, K., & Bezemer, J. M. (2002) · Biomaterials · doi:10.1016/s0142-9612(02)00220-x · Cited by 59 · see citing works
Burugapalli, K., Koul, V., & Dinda, A. K. (2003) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.10117 · Cited by 57 · see citing works
The release of diazepam from poly(hydroxybutyrate-hydroxyvalerate) microspheres
Chen, J., & Davis, S. S. (2002) · Journal of Microencapsulation · doi:10.1080/02652040110065431 · Cited by 49 · see citing works
Problems associated with subcutaneously implanted glucose sensors.
Gerritsen, M. E. (2000) · Diabetes Care · doi:10.2337/diacare.23.2.143 · Cited by 41 · see citing works
Kostanski, J. W., Dani, B. A., Reynolds, G. A., et al. (2000) · AAPS PharmSciTech · doi:10.1208/pt010427 · Cited by 39 · see citing works
Link, D. P., Strandberg, J. D., Virmani, R., et al. (1996) · Journal of Vascular and Interventional Radiology · doi:10.1016/s1051-0443(96)70868-0 · Cited by 34 · see citing works
Implantable glucose sensors: Present status and future developments
Kerner, W. (2001) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/s-2001-18593 · Cited by 30 · see citing works
Oxaliplatin loaded PLAGA microspheres:
Lagarce, F., Cruaud, O., Deuschel, C., Bayssas, M., Griffon, G., & Benoît, J. (2002) · International Journal of Pharmaceutics · doi:10.1016/s0378-5173(02)00166-7 · Cited by 25 · see citing works
Zilinski, J. L., & Kao, W. J. (2003) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.20079 · Cited by 24 · see citing works
Gómez, C., Blanco, M. D., Bernardo, M. V., et al. (2003) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/s0939-6411(03)00154-1 · Cited by 24 · see citing works
Biosensors: Blockbuster or Bomb? Electrochemical Biosensors for Diabetes Monitoring
Kuhn, L. S. (1998) · The Electrochemical Society Interface · doi:10.1149/2.f06984if · Cited by 20 · see citing works
Janjikhel, R. K., & Adeyeye, C. M. (1999) · Drug Delivery · doi:10.1080/107175499266904 · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Franz, S., Rammelt, S., Scharnweber, D., & Simon, J. C. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.05.078 · Cited by 1,391 · see citing works
Mundargi, R. C., Babu, V. R., Rangaswamy, V., Patel, P., & Aminabhavi, T. M. (2008) · Journal of Controlled Release · doi:10.1016/j.jconrel.2007.09.013 · Cited by 1,025 · see citing works
Biomaterials: Foreign Bodies or Tuners for the Immune Response?
Mariani, E., Lisignoli, G., Borzì, R. M., & Pulsatelli, L. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20030636 · Cited by 706 · see citing works
Drug/device combinations for local drug therapies and infection prophylaxis
Wu, P., & Grainger, D. W. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2005.11.031 · Cited by 491 · see citing works
Biocompatible Materials for Continuous Glucose Monitoring Devices
Nichols, S. P., Koh, A., Storm, W. L., Shin, J. H., & Schoenfisch, M. H. (2013) · Chemical Reviews · doi:10.1021/cr300387j · Cited by 347 · see citing works
Concurrent delivery of dexamethasone and VEGF for localized inflammation control and angiogenesis
Patil, S. D., Papadmitrakopoulos, F., & Burgess, D. J. (2007) · Journal of Controlled Release · doi:10.1016/j.jconrel.2006.10.013 · Cited by 230 · see citing works
Self-citationBhardwaj, U., Sura, R., Papadimitrakopoulos, F., & Burgess, D. J. (2007) · Journal of Diabetes Science and Technology · doi:10.1177/193229680700100103 · Cited by 99 · see citing works
Self-citationA dexamethasone‐loaded PLGA microspheres/collagen scaffold composite for implantable glucose sensors
Ju, Y. M., Yu, B., West, L., Moussy, Y., & Moussy, F. (2010) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.32512 · Cited by 44 · see citing works
The Role of Macrophages in the Foreign Body Response to Implanted Biomaterials
Yu, T., Tutwiler, V. J., & Spiller, K. (2015) · Biomaterials in Regenerative Medicine and the Immune System · doi:10.1007/978-3-319-18045-8_2 · Cited by 39 · see citing works
Dang, T. T., Bratlie, K. M., Bogatyrev, S. R., Chen, X. Y., Langer, R., & Anderson, D. G. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.02.048 · Cited by 38 · see citing works
- Authors
- Patil, S. D., Papadimitrakopoulos, F., & Burgess, D. J.
- Affiliations
- University of Connecticut (US)
- ORCID
- Burgess, Diane J.
- Venue
- Diabetes Technology & Therapeutics
- Publisher
- SAGE Publications
- Published
- 2004-12
- Volume
- 6
- Issue
- 6
- Pages
- 887-897
- ISSN
- 1520-9156 (ISSN-L)
- 1557-8593
- OpenAlex
- W2094159150
- Cited by
- 135
- References
- 31
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 1 · 2020: 6 · 2019: 8 · 2018: 8 · 2017: 8 · 2016: 7 · 2015: 11 · 2014: 8 · 2013: 5 · 2012: 13
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Technology & Therapeutics (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, composite coatings, inflammation control, fibrosis, sustained drug release, biocompatibility, in vitro-in vivo correlation
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Animals, Anti-Inflammatory Agents, Non-Steroidal, Dexamethasone, Microspheres, Polyglycolic Acid, Polymers, Polyvinyl Alcohol, United States, Drug Monitoring, Lactic Acid, Hydrogel, Polyethylene Glycol Dimethacrylate, Models, Animal, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
