Antimicrobial resistance is a dramatic global threat; however, the slow progress of new antibiotic development has impeded the identification of viable alternative strategies. Natural antioxidant-based antibacterial approaches may provide potent therapeutic abilities to effectively block resistance microbes’ pathways. While essential oils (EOs) have been reported as antimicrobial agents, its application is still limited ascribed to its low solubility and stability characters; additionally, the related biomolecular mechanisms are not fully understood. Hence, the study aimed to develop a nano-gel natural preparation with multiple molecular mechanisms that could combat bacterial resistance in an acne vulgaris model. A nano-emulgel of thyme/clove EOs (NEG8) was designed, standardized, and its antimicrobial activity was screened in vitro and in vivo against genetically identified skin bacterial clinical isolates (Pseudomonas stutzeri, Enterococcus faecium and Bacillus thuringiensis). As per our findings, NEG8 exhibited bacteriostatic and potent biofilm inhibition activities. An in vivo model was also established using the commercially available therapeutic, adapalene in contra genetically identified microorganism. Improvement in rat behavior was reported for the first time and NEG8 abated the dermal contents/protein expression of IGF-1, TGF-β/collagen, Wnt/β-catenin, JAK2/STAT-3, NE, 5-HT, and the inflammatory markers; p(Ser536) NF-κBp65, TLR-2, and IL-6. Moreover, the level of dopamine, protective anti-inflammatory cytokine, IL-10 and PPAR-γ protein were enhanced, also the skin histological structures were improved. Thus, NEG8 could be a future potential topical clinical alternate to synthetic agents, with dual merit mechanism as bacteriostatic antibiotic action and non-antibiotic microbial pathway inhibitor.

Voriconazole (VRC) is a new triazole antifungal drug. Curcumin (CRM) is an herbal drug with strong antifungal activity. This study aimed to prepare polymeric nanosponges (NSs) hydrogel for the topical delivery of VRC and CRM as a combination therapy to enhance drugs solubility and deposition within the skin, boost their antifungal activity, and avoid VRC’s side effects. NSs formulae were prepared utilizing different percentages of ethyl cellulose and polyvinyl chloride. 3² Full factorial designs were utilized to select the optimized nanosponges (ONS) which composed of 0.5% EC and 0.5% PVA and showed the minimum PS (155.47 ± 4.65 nm) and PDI (0.34 ± 0.02), and the maximum PY % (71.53 ± 2.01%), ZP (-26.96 ± 1.52 mV), and EE% (72.31 ± 3.42%). The ONS (F1) was amalgamated with CRM in varying ratios and subsequently transformed into three combined NS hydrogels (C1, C2, and C3). C2 showed stronger antifungal activity with 2.91- and 4.16-fold compared to C1 and C3, respectively. The optimized combined NS (C2) showed higher skin deposition by 2.25- and 3.50-fold compared to traditional VRC and CRM hydrogel, respectively. The in vivo microbial count and histopathological studies confirmed the superiority of the antifungal efficacy of C2 hydrogel rather than oral CRM and VRC suspension. Hence, NSs hydrogel can be considered a promising carrier for the topical delivery of VRC and CRM. The promising outcomes of the OCNS hydrogel in the male albino rats highlight the need for further human clinical studies to assess the OCNS hydrogel’s safety and efficacy. Graphical Abstract

Bottle gourd (BG) oil (family Cucurbitaceae) has several pharmacological activities including a reduction of the hazard of cardiovascular and atherosclerosis conditions. This work aimed to develop and optimize self-dispersing lipid formulations (SDLFs) of BG oil by applying a full 3² factorial design. The formulation variables (oil concentration and surfactant mixture ratio) showed an obvious impact on the characters of the prepared BG-SDLFs including droplet size (DS), polydispersity index (PDI), emulsification time (ET), and transmission percentage (Tr%). The optimum BG-SDLF composed of 30% oil and Tween 80/Cremophor^® RH40 (1:1) showed good emulsification characteristics and a better drug release profile compared with BG oil. In vivo study in isoproterenol-injected rats showed that BG oil and the optimized BG-SDLF improved cardiac function, by elevating the miRNA-23a gene expression level and decreasing miRNA-21 gene expression. They also caused the inhibition of the plasma B-type natriuretic peptide (BNP), N-terminal proatrial natriuretic peptide (NT-pro-BNP), cystatin c, galectin-3, lipoprotein-associated phospholipase A2 (Lp-PLA2), matrix metallopeptidase 2 (MMP2), cardiac troponin I (cTnI), and cardiac troponin T (cTnT). Our study demonstrated that BG oil and the optimized BG-SDLF provided a cardioprotection against isoproterenol-induced cardiac toxicity with better results in groups treated with the optimized BG-SDLF.