Dawoud M.H.S.Yassin G.E.Ghorab D.M.Morsi N.M.Department of PharmaceuticsFaculty of PharmacyOctober University for Modern Sciences and Arts(MSA University)GizaEgypt; Department of Pharmaceutics and Industrial PharmacyFaculty of PharmacyAl-Azhar UniversityCairoEgypt; Department of Pharmaceutics and Industrial PharmacyFaculty of PharmacyCairo UniversityCairoEgypt2020-01-092020-01-09201915309932https://doi.org/10.1208/s12249-019-1363-6PubMed ID 30963353https://t.ly/vejlAScopusMSA Google ScholarThe present study deals with the formulation of topical insulin for wound healing with extended stability and sustained release, by applying quality by design concepts. Insulin has been promoted as a promising therapeutic wound healing agent. Topical formulation of insulin faced major problems, as it cannot be delivered safely to the wound with a controlled rate. Formulation of insulin-loaded vesicles in optimized bio-adhesive hydrogels has been explored to ensure a safe delivery of insulin to wounds in a controlled manner. Quality by design (QbD) was applied to study the effect of several critical process parameters on the critical quality attributes. Ishikawa diagram was used to identify the highest risk factors, which were screened by a fractional factorial design and augmented by Box�Behnken design. The optimized formula was incorporated into a mucoadhesive gel, which was further subjected to stability and clinical studies. An optimized formula was obtained with a particle size of 257.751�nm, zeta potential ? 20.548�mv, 87.379% entrapment efficiency, and a release rate of 91.521�?g/cm2/h. The results showed that liposomal insulin remained stable for 6�months in aqueous dispersion state at 4�C. Moreover, the release was sustained up to 24�h. The clinical study showed an improvement in the wound healing rate, 16 times, as the control group, with magnificent reduction in the erythema of the ulcer and no signs of hypoglycemia. Insulin-loaded liposomal chitosan gel showed a promising drug delivery system with high stability and sustained release. � 2019, American Association of Pharmaceutical Scientists.EnglishOctober University for Modern Sciences and Artsجامعة أكتوبر للعلوم الحديثة والآدابUniversity of Modern Sciences and ArtsMSA Universityinsulinishikawa diagramliposomesquality by designwound healingchitosaninsulinliposomechitosaninsulinliposomeadultagedArticlecase studyclinical articlecontrolled studydrug designdrug diffusiondrug formulationdrug hydrolysisdrug qualitydrug stabilityencapsulationexperimental designfactorial designgelhumanhuman cellin vitro studyliposomal deliverymucoadhesionparticle sizepriority journalrandomized controlled trialsingle blind proceduresustained drug releaseviscometrywound healingzeta potentialdelayed release formulationdrug delivery systemdrug effecthydrogelpharmacologywound healingChitosanDelayed-Action PreparationsDrug Delivery SystemsHydrogelsInsulinLiposomesParticle SizeWound HealingArticlehttps://doi.org/10.1208/s12249-019-1363-6PubMed ID 30963353