Carbopol 934

KA was purchased from Shaanxi Sangherb Biotech (Shaanxi, China). The water-soluble polymer Carbopol-934 (poly acrylic acid with molecular weight average 450,000) and Tween-80 were supplied by Sigma Aldrich (Darmstadt, Germany). Distilled water was acquired from the research laboratory of Gomal University, D. I. K. (Khyber Pakhtoonkhwa, Pakistan), as were ethanol, acetone, phosphate buffer (pH 6.8 and 7.4) and methanol.

Poly(ε-caprolactone) (PCL) (MW = 14,000 Da), carvacrol (>98% purity), Poloxamer^® 407, Poly(vinyl alcohol)(PVA) (MW = 36,000 Da), Carbopol^® 934, acetone (>99.5%), Mueller Hinton Broth and lipase from Pseudomonas cepacia (≥30 U/mg) were procured from Sigma Aldrich, Hamburg, Germany. Dimethyl sulfoxide (DMSO) and triethanolamine were obtained from Merck kGaA, Darmstadt, Germany. Gluteraldehyde was obtained from Daejung Chemicals and Metals Co., Ltd. Shiheung, Korea. All reagents used were of analytical grade.

Chemicals for diabetes induction (STZ, citric acid, sodium citrate), and hydrogel formation (sodium metabisulfite, sodium methylparaben, sodium propylparaben, and carbopol 934) were purchased from Sigma Aldrich (USA). Cefepime antibiotics were provided from Pharco Pharmaica Company, Cairo, Egypt. The plant clove (S. aromaticum) was obtained from a herbal market at Mansoura city (100 km North Cairo, Egypt), identified morphologically in the Department of Botany Faculty of Science Mansoura University, Egypt, and the plant name was checked with http://www.theplantlist.org (accessed on 2 March 2022) and http://ipni.org/urn:lsid:ipni.org:names:601421-1 (accessed on 2 March 2022). Additionally, the clove is listed in the European pharmacopeia (EMA/HMPC/475451/2020 & EMA/HMPC/534924/2010 & EMA/HMPC/534946/2010 & EMA/HMPC/534948/2010).

Gel base was prepared by dispersing carbopol 934 (Hi-media, India) in distilled water with constant stirring at moderate speed for overnight. Oil phase of the emulsion was made with cetomacrogol 1000, cetostearyl alcohol, white soft paraffin, propylene glycol in light liquid paraffin (Hi-media, India). Aqueous phase was prepared by dissolving peptides (0.5% w/v) in distilled water. The oily and aqueous phases were separately incubated in a water bath at 60°C. Upon obtaining uniformity, oily phase was added to the aqueous phase with continuous stirring. Pre-heated gel base dispersion of carbopol 934 and vitamin ETPGS (Sigma, United States) were added to the emulsion steadily with continuous stirring to obtain homogenized gel. The temperature of the formulation was lowered to 40°C and isopropyl alcohol was added with continuous stirring. The pH was maintained at 6.8 ± 0.2 using saturated solution of citric acid. In vitro emulgel was characterized for its visual appearance under the microscope for the presence of any particle or grittiness. The pH of emulgel was determined by digital pH meter (Contech, India) by dissolving gel in distilled water. Gel extrudability or oozing out from the collapsible tube was determined by physical squeezing from a tube. Gel viscosity was measured using viscometer (Brookfield DV-l Prime, United States).

Bacitracin zinc was purchased from Wilshire Laboratories, Lahore, Pakistan. Polyethylene glycol-8000 (PEG-8000) was purchased from Merk, Darmstadt, Germany. Acrylic acid (AA) from Daejung ltd. Carbopol 934 from Sigma-Aldrich, Schnelldorf, Germany. Ammonium persulfate (APS) from Merck LGea, Darmstadt, Germany. N, N’-Methylenebisacrylamide (MBA) from Sigma-Aldrich, Schnelldorf, Germany. Tween 80 was obtained from Hoover Pharmaceuticals, Lahore, Pakistan. Sodium hydroxide (NaOH), Potassium dihydrogen phosphate (KH₂PO₄), Hydrochloric acid (HCL) and Methanol were procured from Merck, Darmstadt, Germany. Distilled water from Research Lab, University of Lahore, Lahore, Pakistan.

Nystatin and carboxypolymethylene (carbopol, Carbopol^® 934) were purchased from Sigma-Aldrich Japan (Tokyo, Japan) and Serva (Heidelberg, Germany), respectively. Cytochalasin D, propyl p-hydroxybenzoate, isoflurane and commercially available ketoprofen powder (particle size, 7.7 ± 0.28 μm, means ± S.E.) were provided by Wako Pure Chemical Industries, Ltd. (Osaka, Japan). Rottlerin and dynasore were purchased from Nacalai Tesque (Kyoto, Japan) and methylcellulose (MC, SM-4) was obtained from Shin-Etsu Chemical Co., Ltd. (Tokyo, Japan). All other chemicals used were of the highest purity commercially available.