Sesamol-Loaded PLGA Nanosuspension for Accelerating Wound Healing in Diabetic Foot Ulcer in Rats

© 2020 Gourishetti et al..

BACKGROUND: Diabetic foot ulcer is an intractable complication of diabetes, characterized by the disturbed inflammatory and proliferative phases of wound healing. Sesamol, a phenolic compound, has been known for its powerful antioxidant, anti-inflammatory, anti-hyperglycaemic and wound healing properties. The aim of the present study was to develop a sesamol nano formulation and to study its effect on the various phases of the wound healing process in diabetic foot condition.

METHODS: Sesamol-PLGA (SM-PLGA) nanosuspension was developed  using nanoprecipitation method. TEM, in vitro drug release assay and in vivo pharmacokinetic studies were performed for the optimised formulation. Diabetic foot ulcer (DFU) in high fat diet (HFD)-fed streptozotocin-induced type-II diabetic animal model was used to assess the SM-PLGA nanosuspension efficacy. SM-PLGA nanosuspension was administered by oral route. TNF-α levels were estimated using ELISA and Western blot analysis was performed to assess the effect on the expression of HSP-27, ERK, PDGF-B and VEGF in wound tissue. Wound re-epithelization, fibroblast migration, collagen deposition and inflammatory cell infiltration were assessed by H&E and Masson's trichrome staining. Effect on angiogenesis was assessed by CD-31 IHC staining in wound sections.

RESULTS: The optimized SM-PLGA nanosuspension had an average particle size of <300 nm, PDI<0.200 with spherical shaped particles. Approximately 80% of the drug was released over a period of 60 h in in vitro assay. Half-life of the formulation was found to be 13.947 ± 0.596 h. SM-PLGA nanosuspension treatment decreased TNF-α levels in wound tissue and accelerated the collagen deposition. Whereas, HSP-27, ERK, PDGF-B and VEGF expression increased and improved new blood vessels' development. Rapid re-epithelization, fibroblast migration, collagen deposition and reduced inflammatory cell infiltration at the wound site were also observed.

CONCLUSION: Results indicate that sesamol-PLGA nanosuspension significantly promotes the acceleration of wound healing in diabetic foot ulcers by restoring the altered wound healing process in diabetic condition.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:15

Enthalten in:

International journal of nanomedicine - 15(2020) vom: 26., Seite 9265-9282

Sprache:

Englisch

Beteiligte Personen:

Gourishetti, Karthik [VerfasserIn]
Keni, Raghuvir [VerfasserIn]
Nayak, Pawan Ganesh [VerfasserIn]
Jitta, Srinivas Reddy [VerfasserIn]
Bhaskaran, Navya Ajitkumar [VerfasserIn]
Kumar, Lalit [VerfasserIn]
Kumar, Nitesh [VerfasserIn]
Krishnadas, Nandakumar [VerfasserIn]
Shenoy, Rekha Raghuveer [VerfasserIn]

Links:

Volltext

Themen:

1SIA8062RS
5W494URQ81
9002-89-5
94IEA0NV89
Angiogenesis
Benzodioxoles
Blood Glucose
Controlled release
Diabetes
Diabetic foot ulcer
EC 2.7.11.24
Extracellular Signal-Regulated MAP Kinases
HSP27 Heat-Shock Proteins
Hspb1 protein, rat
Journal Article
Nanosuspension
PLGA
Phenols
Platelet-Derived Growth Factor
Polylactic Acid-Polyglycolic Acid Copolymer
Polyvinyl Alcohol
Re-epithelization
Sesamol
Streptozocin
Suspensions
TNF-α
Tumor Necrosis Factor-alpha
Vascular Endothelial Growth Factor A
Wound healing

Anmerkungen:

Date Completed 18.12.2020

Date Revised 18.04.2022

published: Electronic-eCollection

Citation Status MEDLINE

doi:

10.2147/IJN.S268941

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM318288125