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Drug resistance substantially compromises antibiotic therapy and poses a serious threat to public health. Fusidic acid (FA) is commonly used to treat staphylococcal infections, such as pneumonia, osteomyelitis and skin infections. However, Gram-negative bacteria have natural resistance to FA, which is almost restrained in cell membranes due to the strong interactions between FA and phospholipids. Herein, we aim to utilize the strong FA–phospholipid interaction to pre-form a complex of FA with the exogenous phospholipid. The FA, in the form of an FA–phospholipid complex (FA-PC), no longer interacts with the endogenous membrane phospholipids and thus can be delivered into bacteria cells successfully. We found that the water solubility of FA (5 µg/mL) was improved to 133 µg/mL by forming the FA-PC (molar ratio 1:1). Furthermore, upon incubation for 6 h, the FA-PC (20 µg/mL) caused a 99.9% viability loss of E. coli and 99.1% loss of P. aeruginosa, while free FA did not work. The morphology of the elongated bacteria cells after treatment with the FA-PC was demonstrated by SEM. The successful intracellular delivery was shown by confocal laser scanning microscopy in the form of coumarin 6-PC (C6-PC), where C6 served as a fluorescent probe. Interestingly, the antibacterial effect of the FA-PC was significantly compromised by adding extra phospholipid in the medium, indicating that there may be a phospholipid-based transmembrane transport mechanism underlying the intracellular delivery of the FA-PC. This is the first report regarding FA-PC formation and its successful reversing of Gram-negative bacteria resistance to FA, and it provides a platform to reverse transmembrane delivery-related drug resistance. The ready availability of phospholipid and the simple preparation allow it to have great potential for clinical use. [ABSTRACT FROM AUTHOR]

Treatment of androgenetic alopecia (AGA) with concurrent electrodynamic microneedling and 5% minoxidil may further stimulate hair growth. To evaluate the efficacy of microneedling combined with 5% minoxidil in Chinese male AGA patients and to explore the underlying mechanisms. Seventy-one male volunteers with AGA completed the entire trial and follow-up. The first group (n = 23) received only 5% minoxidil twice daily for 24 weeks; the second group (n = 23) received only microneedle therapy every 3 weeks for eight treatments; and the third group (n = 25) received the combination treatment for a total of 24 weeks. Changes in hair density and diameter were evaluated before and after treatment every 3 weeks, and patients were followed up at 6 months after the final treatment. In the combination group, a PCR array was used to detect the expression of molecules in the Wnt/β-catenin pathway within the hair loss sites on top of the head before and after treatment and within the scalp tissues from non-hair loss sites on top of the head. The tissues were obtained by punches in the most severe area of hair loss on top of the head and in the adjacent normal hair area without hair loss. Real-time quantitative PCR and western blotting were used to further examine changes in the differentially expressed molecules identified by PCR array (FZD3) and in molecules in the Wnt/β-catenin signaling pathway closely related to hair growth (β-catenin and LEF-1). Compared to single minoxidil or single microneedle treatment, the combination therapy showed superior therapeutic effects clinically, with further upregulation of FZD3, β-catenin, and LEF-1 expression levels at both mRNA and protein levels in the treated areas. Microneedling combined with 5% minoxidil can improve AGA, and the underlying mechanism may involve activation of the Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

Background and objectives: Most topical medications need a long time to penetrate into the skin owing to the stratum corneum (SC) barrier. The fractional erbium-doped yttrium aluminum garnet (Er:YAG) laser has the ability to disrupt the SC and assist in the delivery of topical drugs to penetrate into the skin. This study was intended to determine whether pretreatment with a painless fractional Er:YAG laser could assist transdermal delivery of topical anesthesia. Materials and methods: In 22 healthy female subjects, three 4 × 3 cm regions on the right forearm were randomized to: fractional laser plus topical lidocaine cream (Group LaserAnes), sham irradiation plus topical anesthesia (Group Anes), and sham irradiation plus sham anesthesia (Group Con). After 5 minutes, each site was treated with yttrium scandium gallium garnet laser to evaluate the pain sensation using the visual analog scale. Results: The average pain scores of Group LaserAnes, Group Anes, and Group Con are 3.74 ± 1.93, 4.90 ± 2.09, and 5.19 ± 2.15, respectively. The pain score of Group LaserAnes has a 25.57% reduction compared to Group Anes (p < 0.001) and a 28.70% reduction compared to Group Con (p < 0.001). There is no significant pain reduction for Group Anes compared with Group Con (p = 0.094). Conclusions: Pretreatment using fractional Er:YAG laser before topicals might be an effective method for drug delivery. [ABSTRACT FROM AUTHOR]

Developing the delivery systems with high therapeutic efficacy and low side effects is of great interest and significance for anticancer therapy. Compared to the high cost in synthesizing new chemotherapeutic drugs, exploring the anticancer potentials of existing chemicals is more convenient and efficient. Sodium bicarbonate (BC), a simple inorganic salt, has shown its tumor inhibition capacity via regulating the acidity of tumor microenvironment. However, the effects of intracytoplasmic BC on tumor growth and the potentials of BC to serve as an anticancer agent are still unknown. Herein, we developed a BC-loaded cationic liposome system (BC-CLP) to deliver BC into the cytosol of cancer cells. The in vitro studies showed that the BC-CLP containing 1% BC (w/v) had a size of 112.9 nm and a zeta potential of 19.1 mV, which reduced the viability of the model cancer cells (human oral squamous cell carcinoma HSC-3 cells) to 13.7%. In contrast, the neutral BC-LP caused less than 50% viability reduction. We further found that BC-CLP released BC directly into cytoplasm via membrane fusion pathway rather than endocytosis, leading to the remarkable increase of cytosolic pH, which may contribute to the anticancer effect of BC-CLP. Our findings indicate that BC-CLP is a potential system for high-efficiency cancer therapy without causing drug-related side effects or resistance. • Sodium bicarbonate (BC) is a potential anticancer agent. • BC-loaded cationic liposome (BC-CLP) delivers BC into the cytosol of cancer cells. • BC-CLP shows great in vitro anticancer activity. • BC-CLP increases the cytosolic pH. [ABSTRACT FROM AUTHOR]