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Intra-articular formulation of GE11-PLGA conjugate-based NPs for dexamethasone selective targeting : in vitro evaluation

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Abstract
Selectively targeted nanoscale drug delivery systems have recently emerged as promising intravenously therapeutic option for most chronic joint diseases. Here, a newly synthetized dodecapeptide (GE11)-polylactide-co-glycolide (PLGA)-based conjugate was used to prepare smart nanoparticles (NPs) intended for intra-articular administration and for selectively targeting Epidermal Growth Factor Receptor (EGFR). GE11-PLGA conjugate-based NPs are specifically uptaken by EGFR-overexpressed fibroblast; such as synoviocytes; which are the primarily cellular component involved in the development of destructive joint inflammation. The selective uptake could help to tune drug effectiveness in joints and to decrease local and systemic side effects. Dexamethasone (DXM) is a glucorticoid drug commonly used in joint disease treatment for both systemic and local administration route. In the present research; DXM was efficiently loaded into GE11-PLGA conjugate-based NPs through an eco-friendly nanoprecipitation method set up for this purpose. DXM loaded GE11-PLGA conjugate-based NPs revealed satisfactory ex vivo cytocompatibility; with proper size (150 nm) and good dimensional stability in synovial fluid. Intra-articular formulation was developed embedding DXM loaded GE11-PLGA conjugate-based NPs into thermosetting chitosan-based hydrogel; forming a biocompatible composite hydrogel able to quickly turn from liquid state into gel state at physiological temperature; within 15 min. Moreover; the use of thermosetting chitosan-based hydrogel extends the local release of active agent; DXM.
Keywords
EGFR targeting, GE11 peptide, PLGA-PEG nanoparticles, chitosan thermosetting hydrogel, intra-articular injection, GROWTH-FACTOR RECEPTOR, RHEUMATOID-ARTHRITIS, DRUG-DELIVERY, IN-SITU, KNEE OSTEOARTHRITIS, PARTICLE-SIZE, NANOPARTICLES, CHITOSAN, SYSTEM, THERAPEUTICS

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Chicago
Chiesa, Enrica, Silvia Pisani, Barbara Colzani, Rossella Dorati, Bice Conti, Tiziana Modena, Kevin Braeckmans, and Ida Genta. 2018. “Intra-articular Formulation of GE11-PLGA Conjugate-based NPs for Dexamethasone Selective Targeting : in Vitro Evaluation.” International Journal of Molecular Sciences 19 (8).
APA
Chiesa, E., Pisani, S., Colzani, B., Dorati, R., Conti, B., Modena, T., Braeckmans, K., et al. (2018). Intra-articular formulation of GE11-PLGA conjugate-based NPs for dexamethasone selective targeting : in vitro evaluation. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 19(8).
Vancouver
1.
Chiesa E, Pisani S, Colzani B, Dorati R, Conti B, Modena T, et al. Intra-articular formulation of GE11-PLGA conjugate-based NPs for dexamethasone selective targeting : in vitro evaluation. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2018;19(8).
MLA
Chiesa, Enrica, Silvia Pisani, Barbara Colzani, et al. “Intra-articular Formulation of GE11-PLGA Conjugate-based NPs for Dexamethasone Selective Targeting : in Vitro Evaluation.” INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 19.8 (2018): n. pag. Print.
@article{8570789,
  abstract     = {Selectively targeted nanoscale drug delivery systems have recently emerged as promising intravenously therapeutic option for most chronic joint diseases. Here, a newly synthetized dodecapeptide (GE11)-polylactide-co-glycolide (PLGA)-based conjugate was used to prepare smart nanoparticles (NPs) intended for intra-articular administration and for selectively targeting Epidermal Growth Factor Receptor (EGFR). GE11-PLGA conjugate-based NPs are specifically uptaken by EGFR-overexpressed fibroblast; such as synoviocytes; which are the primarily cellular component involved in the development of destructive joint inflammation. The selective uptake could help to tune drug effectiveness in joints and to decrease local and systemic side effects. Dexamethasone (DXM) is a glucorticoid drug commonly used in joint disease treatment for both systemic and local administration route. In the present research; DXM was efficiently loaded into GE11-PLGA conjugate-based NPs through an eco-friendly nanoprecipitation method set up for this purpose. DXM loaded GE11-PLGA conjugate-based NPs revealed satisfactory ex vivo cytocompatibility; with proper size (150 nm) and good dimensional stability in synovial fluid. Intra-articular formulation was developed embedding DXM loaded GE11-PLGA conjugate-based NPs into thermosetting chitosan-based hydrogel; forming a biocompatible composite hydrogel able to quickly turn from liquid state into gel state at physiological temperature; within 15 min. Moreover; the use of thermosetting chitosan-based hydrogel extends the local release of active agent; DXM.},
  articleno    = {2304},
  author       = {Chiesa, Enrica and Pisani, Silvia and Colzani, Barbara and Dorati, Rossella and Conti, Bice and Modena, Tiziana and Braeckmans, Kevin and Genta, Ida},
  issn         = {1422-0067},
  journal      = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
  language     = {eng},
  number       = {8},
  pages        = {22},
  title        = {Intra-articular formulation of GE11-PLGA conjugate-based NPs for dexamethasone selective targeting : in vitro evaluation},
  url          = {http://dx.doi.org/10.3390/ijms19082304},
  volume       = {19},
  year         = {2018},
}

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