Development of chloramphenicol whey protein-based microparticles incorporated into thermoresponsive in situ hydrogels for improved wound healing treatment

INTERNATIONAL JOURNAL OF PHARMACEUTICS(2022)

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Abstract
This study focused on the incorporation of chloramphenicol (CAP) into whey protein (WPI) (CAP-MPs) and was further formulated into a thermoresponsive in situ gel for wound healing treatment. CAP micro -particles were produced by two steps emulsification process. The modification of the mixing time and speed, as well as the variation of WPI and CAP concentration, resulted in various particle sizes (0.95 +/- 0.07 to 8.94 +/- 0.32 mu m). The optimum formulation was achieved using 15 % WPI in water, and 2 mL CAP in propylene glycol with a total amount in the mixture was 100 mg, and 5 % oil phase, with homogenization time and speed at 15 min and 7500 rpm, respectively. The characterization of CAP-MP's showed PDI values at 0.110 +/- 0.007, drug entrapment efficiency at 70.64 +/- 1.12 %, and drug loading at 8.80 +/- 0.12 %. SEM analysis of CAP-MPs show-ed spherical, uniform particles dispersed across the surface of the emulsion droplets. FTIR analysis showed strong development of hydrogen bonds proving the encapsulation was effective. Pluronic (R) F127, Pluronic (R) F68, and hydroxypropyl methylcellulose (HPMC) were used for the thermoresponsive hydrogel formulation with desired properties. The gel formulation could provide liquid form at room temperature (25 degrees C) and form a gel at 31 degrees C. This optimum formula was able to increase the bioadhesivity (28160.92 +/- 3902.09 dyne/cm2) as well as the percentage of gels skin occlusivity after 24 h (32.82 +/- 0.004), and to be considered, it did not show hemolytic activities. In an ex vivo antibacterial activity, this combination approach showed a 99.95 % reduction in the -Staphylococcus aureus (SA) population.
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Key words
Antimicrobial,Skin infection,Chloramphenicol,Microparticle,Thermoresponsive-gel,whey -protein
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