Sustained prolonged topical delivery of bioactive human insulin for potential treatment of cutaneous wounds

Hrynyk, Michael; Martins‐Green, Manuela; Barron, Annelise E.; Neufeld, Ronald J.

doi:10.1016/j.ijpharm.2010.07.052

Cited by 49 publications

(39 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the released insulin exhibited a declining trend in the bioactivity of accelerating osteoblast proliferation over the release period. A similar phenomenon was reported by Hrynyk et al [38]. The increasingly acidic microenvironment within degrading microspheres may contribute to the loss of insulin bioactivity [39].…”

Section: Discussionsupporting

confidence: 77%

Sustained local delivery of insulin for potential improvement of peri-implant bone formation in diabetes

Han

Zhang

Lingling

et al. 2012

Sci. China Life Sci.

View full text Add to dashboard Cite

Dental implantation is an effective standard treatment modality to restore missing teeth and maxillofacial defects. However, in diabetics there is an increased risk for implant failure due to impaired peri-implant osseous healing. Early topical insulin treatment was recently shown to normalize diabetic bone healing by rectifying impairments in osteoblastic activities. In this study, insulin/poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared by a double-emulsion solvent evaporation method. Microspheres were then incorporated in fibrin gel to develop a local drug delivery system for diabetic patients requiring implant treatment. In vitro release of insulin from fibrin gel loaded with these microspheres was assessed, and sustained prolonged insulin release over 21 days ascertained. To assess the bioactivity of released insulin and determine whether slow release might improve impaired diabetic bone formation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), alkaline phosphatase (ALP) activity, mineralized nodule formation, and ELISA (enzyme-linked immunosorbent assay) assays were performed. The insulin released from the drug delivery system stimulated cell growth in previously inhibited cells, and ameliorated the impaired bone-forming ability of human MG-63 cells under high glucose conditions. Fibrin gel loaded with insulin/PLGA microspheres shows potential for improving peri-implant bone formation in diabetic patients.insulin, controlled release, peri-implant bone formation, diabetes, hyperglycemia, human MG-63 cells, osteoblastic activity Citation:Han Y, Zhang X Y, E L L, et al. Sustained local delivery of insulin for potential improvement of peri-implant bone formation in diabetes. Sci China Life Sci, 2012, 55: 948 -957,

show abstract

Section: Discussionsupporting

confidence: 77%

Sustained local delivery of insulin for potential improvement of peri-implant bone formation in diabetes

Han

Zhang

Lingling

et al. 2012

Sci. China Life Sci.

View full text Add to dashboard Cite

show abstract

“…Cells were then seeded (4 x 10 5 cells/mL) onto matrigel-coated transwell inserts (8.0 μm polycarbonate membrane, 6.5mm, Corning Costar, Cambridge, UK) and placed into lower chambers containing M199 medium supplemented with 10% FBS, 10 ng/mL VEGF (negative control) and 125 µg/mL of native ranibizumab (positive control) or ranibizumab released from PLGA microparticles. The released ranibizumab was collected as previously described (45) and concentrated to 125 µg/mL using centrifugal concentrators (10 kDa MWCO, Vivaspins, Vivascience, Hannover, Germany) which were spun at 4 krpm, 4 °C, for 15 mins (Centrifuge 5804R, Eppendorf, Germany). 125 µg/mL of ranibizumab was selected to represent the therapeutic concentration following injection into the human vitreous.…”

Section: Effect Of Ranibizumab Released From Plga Microparticles On Ementioning

confidence: 99%

PLGA Microparticles Entrapping Chitosan-Based Nanoparticles for the Ocular Delivery of Ranibizumab

et al. 2016

View full text Add to dashboard Cite

Age-related macular degeneration (AMD) is the leading cause of certified vision loss worldwide. The standard treatment for neovascular AMD involves repeated intravitreal injections of therapeutic proteins directed against vascular endothelial growth factor, such as ranibizumab. Biodegradable polymers, such as poly(lactic-co-glycolic acid) (PLGA), form delivery vehicles which can be used to treat posterior segment eye diseases, but suffer from poor protein loading and release. This work describes a 'system-within-system', PLGA microparticles incorporating chitosan-based nanoparticles, for improved loading and sustained intravitreal delivery of ranibizumab. Chitosan-N-acetyl-L-cysteine (CNAC) was synthesized and its synthesis confirmed using FT-IR and 1 H NMR. Chitosan-based nanoparticles comprised of CNAC, CNAC/tripolyphosphate (CNAC/TPP), chitosan, chitosan/TPP (chit/TPP) or chit/TPP-hyaluronic acid (chit/TPP-HA) were incorporated in PLGA microparticles using a modified w/o/w double emulsion method. Nanoparticles and final nanoparticles-within-microparticles were characterized for their protein-nanoparticle interaction, size, zeta potential, morphology, protein loading, stability, in vitro release, in vivo anti-angiogenic activity and effects on cell viability. The prepared nanoparticles were 17 -350 nm in size and had zeta potentials of -1.4 to +12 mV. Microscopic imaging revealed spherical nanoparticles on the surface of PLGA microparticles for preparations containing chit/TPP, CNAC and CNAC/TPP. Ranibizumab entrapment efficiency in the preparations varied between 13 -69% and was highest for the PLGA microparticles containing CNAC nanoparticles. This preparation also showed the slowest release with no initial burst release compared to all other preparations. Incorporation of TPP to this formulation increased the rate of protein release and reduced entrapment efficiency. PLGA microparticles containing chit/TPP-HA showed the fastest and near-complete release of ranibizumab. All of the prepared empty particles showed no effect on cell viability up to a concentration of 12.5 mg/mL. Ranibizumab released from all preparations maintained its structural integrity and in vitro activity. The chit/TPP-HA preparation enhanced anti-angiogenic activity and may provide a potential biocompatible platform for enhanced anti-angiogenic activity in combination with ranibizumab. In conclusion, the PLGA microparticles containing CNAC nanoparticles, showed significantly improved ranibizumab loading and release profile. This novel drug delivery system may have potential for improved intravitreal delivery of therapeutic proteins, thereby reducing the frequency, risk and cost of burdensome intravitreal injections.

show abstract

“…Furthermore, an in vitro scratch assay in HaCat cells established that insulin released from PLGA microspheres stimulated rapid cell migration following an induced scratch. Hrynyk et al [41] suggested that crystalline insulin encapsulated within PLGA microspheres offers potential for long-term and controlled delivery of bioactive insulin for topical delivery devices and could have signi icant clinical applications.…”

Section: Pharmaceutical Applications Of Insulin In Wound Healingmentioning

confidence: 99%

The Role of Insulin in Wound Healing Process: Mechanism of Action and Pharmaceutical Applications

DH¹

2016

JAPLR

View full text Add to dashboard Cite

Sustained prolonged topical delivery of bioactive human insulin for potential treatment of cutaneous wounds

Cited by 49 publications

References 60 publications

Sustained local delivery of insulin for potential improvement of peri-implant bone formation in diabetes

Sustained local delivery of insulin for potential improvement of peri-implant bone formation in diabetes

PLGA Microparticles Entrapping Chitosan-Based Nanoparticles for the Ocular Delivery of Ranibizumab

The Role of Insulin in Wound Healing Process: Mechanism of Action and Pharmaceutical Applications

Contact Info

Product

Resources

About