Solid lipid nanoparticles cyclodextrin-decorated incorporated into gellan gum-based dry floating in situ delivery systems for controlled release of bioactive compounds of safflower (Carthamus tinctorius. L): A proof of concept study in biorelevant media.

Safflower (Carthamus tinctorius L.) has been explored as a source of natural antioxidant. However, quercetin 7-O-beta-D-glucopyranoside and luteolin 7-O-beta-D-glucopyranoside, as its bioactive compounds, possessed poor aqueous solubility, limiting its efficacy. Here, we developed solid lipid nanoparticles (SLNs) decorated with hydroxypropyl beta-cyclodextrin (HPßCD) incorporated into dry floating gel in situ systems to control the release of both compounds. Using Geleol® as a lipid matrix, SLNs were <200 nm in size with >80 % of encapsulation efficiency. Importantly, following the decoration using HPßCD, the stability of SLNs in gastric environment was significantly improved. Furthermore, the solubility of both compounds was also enhanced. The incorporation of SLNs into gellan gum-based floating gel in situ provided desired flow and floating properties, with <30 s gelation time. The floating gel in situ system could control the release of bioactive compounds in FaSSGF (Fasted-State Simulated Gastric Fluid). Furthermore, to assess the effect of food intake on release behavior, we found that the formulation could show a sustained release pattern in FeSSGF (Fed-State Simulated Gastric Fluid) for 24 h after being released in FaSGGF for 2 h. This indicated that this combination approach could be a promising oral delivery for bioactive compounds in safflower.

Enhancement in Site-Specific Delivery of Chloramphenicol Using Bacterially Sensitive Microparticle Loaded Into Dissolving Microneedle: Potential For Enhanced Effectiveness Treatment of Cellulitis.

One of the biggest challenges in infectious disease treatment is the existence of bacterial infections in underskin wound tissue, such as cellulitis. Compared to other treatments, it is harder for antibacterial drugs to penetrate the physical barrier on the affected skin with a nonspecific target, making conventional therapy for cellulitis infection more difficult and considered. In this novel research, we pioneer a combined strategy of dissolving microneedles (MNs) and bacteria-sensitive microparticles (MPs) for enhanced penetration and targeted delivery of chloramphenicol (CHL) to the infection site specifically. The polycaprolactone polymer was used to make MPs because of its sensitivity to bacterial enzyme stimuli. The best microparticle formulation was discovered and optimized using the Design-Expert application. Furthermore, this study evaluated the antibacterial activity of MPs in vitro and in vivo on the mutant Drosophila larval infection model. This strategy shows improvement in the antibacterial activity of MPs and higher retention duration compared to conventional cream formulation, and the inclusion of these MPs into dissolving MNs was able to greatly improve the dermatokinetic characteristics of CHL in ex vivo evaluation. Importantly, the antimicrobial efficacy in an ex vivo infection model demonstrated that, following the use of this strategy, bacterial bioburdens decreased by up to 99.99% after 24 h. The findings offered a proof of concept for the enhancement of CHL dermatokinetic profiles and antimicrobial activities after its preparation into bacteria-sensitive MPs and distribution by MNs. Future research should investigate in vivo effectiveness in an appropriate animal model.

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

This study focused on the incorporation ofchloramphenicol (CAP)intowhey protein (WPI)(CAP-MPs) and was further formulated into a thermoresponsivein situgel for wound healing treatment.CAP microparticleswereproduced by two steps emulsification process.The modification ofthe mixing time and speed, as well as the variation of WPI and CAP concentration, resulted in various particle sizes(0.95 ± 0.07to 8.94 ± 0.32 µm). The optimum formulation was achieved using 15 % WPI in water, and 2 mL CAP in propylene glycol withatotal 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 at70.64 ± 1.12 %,and drug loading at 8.80 ± 0.12 %.SEM analysis of CAP-MPs showedspherical, uniform particlesdispersed across the surface of the emulsion droplets.FTIR analysis showed strong development of hydrogen bonds proving the encapsulation was effective. Pluronic® F127, Pluronic® F68, and hydroxypropyl methylcellulose (HPMC)were used for the thermoresponsive hydrogel formulation with desired properties. The gel formulationcouldprovideliquid form at room temperature (25 °C) andformagel at 31 °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 anex vivoantibacterial activity, this combination approach showed a 99.95 % reduction in theStaphylococcus aureus(SA) population.