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Title:	Healing efficacy of dual-action gels containing dsirna loaded gold nanoparticles for diabetic wound therapy
Supervisor:	Haliza Katas, Professor Dr.
Keywords:	Universiti Kebangsaan Malaysia -- Dissertations Dissertations, Academic -- Malaysia Diabetes Mellitus - therapy Nanoparticles
Issue Date:	3-Apr-2021
Description:	Therapy that is directed to manage diabetic wounds by offering correction of biological abnormalities caused by hyperglycaemia and prevention of infection is currently not available. Hence, this invention was developed by offering dual therapy consisting Dicer subtract small interfering RNA (DsiRNA) and gold nanoparticles (AuNPs) to inhibit prostaglandin transporter and act as an antibacterial agent, respectively, for treating diabetic wound. AuNPs were synthesised via green synthesis using cold and hot sclerotium of Lignosus rhinocerotis (Tiger Milk Mushroom) extracts (CLRE and HLRE, respectively) and stabilised with a biopolymer chitosan (CS) to prevent particle aggregation. DsiRNA was bind to the surface of lyophilised AuNPs (DsiRNA-AuNPs) prior to loading into pluronic gels. The smallest size of AuNPs was obtained with the use of 0.25 mg/mL CLRE (202 ± 49 nm) and 0.06 mg/mL HLRE (190 ± 31 nm). Both AuNPs also displayed high antibacterial activity against gram positive (Staphylococcus aureus) and negative bacteria (Pseudomonas aeruginosa and Escherichia coli) and were relatively non-toxic to human dermal fibroblasts (HDFs) as determined by in-vitro cell viability tests at the concentration range of 0.06-0.25 mg/mL. The percent of DsiRNA entrapment efficiency onto the surface of AuNPs reduced by CLRE and HLRE were in the range of 83±2 to 84±11% and 85±6 to 88±9%, respectively, when the concentration was increased from 0.06 to 0.25 mg/mL. The gels containing DsiRNAAuNPs exhibited good spreadability and acceptable viscosity with the gelling temperature of 25.8 ± 1.3°C to 29.2 ± 1.3°C. Pluronic gels containing DsiRNA-AuNPs enhanced cell proliferation of HDFs within 48 h which is comparable to positive control (HDFs treated with Dulbecco's Modified Eagle Medium only). Moreover, the cell migration rate of gels containing DsiRNA-AuNPs reduced by HLRE (5594 ± 1514 – 9390 ± 380 μm/h) was higher than CLRE (1934 ± 488 – 5300 ± 770 μm/h). Wounds treated by pluronic gels containing DsiRNA-AuNPs healed better than the positive control (wound treated with Intrasite gel) as demonstrated in in-vivo study using Wistar rat's diabetic model. The healing efficacy of both was also comparable to non-diabetic group during 14 days of therapy. The percent of wound closure was 92.7 ± 2.2% and 85.1±7.3% for DsiRNA-AuNPs reduced by HLRE and CLRE, higher than the groups treated by Intrasite gel (74.86±13.3%) and non-diabetic (90.26±3.4%). Moreover, pluronic gels containing DsiRNA-AuNPs improved the production of vascular endothelial growth factor-A (VEGF-A) and prostaglandin E2 (PGE2), signal proteins that enhance angiogenesis process in wound healing. In conclusion, Pluronic gel containing DsiRNA-AuNPs reduced by both HLRE and CLRE are expected to be useful as a healing promoter for treating diabetic wounds,Doktor Falsafah(PhD)
Pages:	245
Call Number:	WK815.A286h 2021 9 tesis
Publisher:	UKM, Kuala Lumpur
Appears in Collections:	Faculty of Pharmacy / Fakulti Farmasi

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