Enhancing Permeation of Drug Molecules Across the Skin via Delivery in Nanocarriers: Novel Strategies for Effective Transdermal Applications.

The transdermal route of administration provides numerous advantages over conventional routes i.e., oral or injectable for the treatment of different diseases and cosmetics applications. The skin also works as a reservoir, thus deliver the penetrated drug for more extended periods in a sustained manner. It reduces toxicity and local irritation due to multiple sites for absorption and owes the option of avoiding systemic side effects. However, the transdermal route of delivery for many drugs is limited since very few drugs can be delivered at a viable rate using this route. The stratum corneum of skin works as an effective barrier, limiting most drugs' penetration posing difficulty to cross through the skin. Fortunately, some non-invasive methods can significantly enhance the penetration of drugs through this barrier. The use of nanocarriers for increasing the range of available drugs for the transdermal delivery has emerged as a valuable and exciting alternative. Both the lipophilic and hydrophilic drugs can be delivered via a range of nanocarriers through the stratum corneum with the possibility of having local or systemic effects to treat various diseases. In this review, the skin structure and major obstacle for transdermal drug delivery, different nanocarriers used for transdermal delivery, i.e., nanoparticles, ethosomes, dendrimers, liposomes, etc., have been discussed. Some recent examples of the combination of nanocarrier and physical methods, including iontophoresis, ultrasound, laser, and microneedles, have also been discussed for improving the therapeutic efficacy of transdermal drugs. Limitations and future perspectives of nanocarriers for transdermal drug delivery have been summarized at the end of this manuscript.

Tai Chi on bone mineral density of postmenopausal osteoporosis: A protocol for systematic review and meta-analysis.

BACKGROUND: Osteoporosis is a clinically common metabolic disease, especially in postmenopausal women. Tai Chi might be beneficial in osteoporosis patients. This study will be performed to examine the effects of Tai Chi on bone mineral density of postmenopausal osteoporosis. METHODS: We will search the electronical databases and hand-searching journals or reference lists. The study screening and data extraction will be carried out by 2 investigators independently. The primary outcome is bone mineral density (lumbar spine, Ward's triangle, trochanter, proximal femur, femoral neck, or total hip). Secondary outcomes are pain score, alkaline phosphatase, osteocalcin, and adverse effects. Review Manager V.5.3 software will be used to compute the data. RESULTS: The results of the study will provide a reliable evidence to assess the effects of Tai Chi on bone mineral density of postmenopausal osteoporosis. CONCLUSION: The conclusion of our systematic review will answer whether Tai Chi is an effective intervention to improve bone mineral density of postmenopausal osteoporosis.

Effects of mometasone furoate-impregnated biodegradable nasal dressing on endoscopic appearance in healing process following endoscopic sinus surgery: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Postoperative care is an important factor affecting the outcome of endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). The aim of this study was to test the effect of mometasone furoate (MF)-soaked biodegradable nasal dressings (BNDs) on endoscopic appearance in CRS patients with nasal polyps (CRSwNP) after ESS. METHODS: This study was a prospective, randomized, double-blinded, placebo-controlled study. A total of 64 CRSwNP patients with bilateral ESS were enrolled and randomly given 4 mL or 8 mL of MF-soaked BNDs (NasoPore) in 1 nasal cavity and the same amount of normal saline-soaked BNDs in the contralateral side. The BNDs were removed on the 7th or 14th postoperative day. Perioperative sinus endoscopy (POSE) and Lund-Kennedy scores were collected, on the 7th or 14th postoperative days and at 1, 2, and 3 postoperative months. RESULTS: The POSE and Lund-Kennedy scores showed that in the 4-mL, 1-week group, no significant differences between the sides treated with MF-soaked BNDs and the normal saline-soaked control were observed at any postoperative visits. In the 4-mL, 2-week group, significant differences were found at the 2-week and 1-month postoperative visits but not at the 2-month and 3-month visits. In the 8-mL, 1-week group, significant differences were found at the 1-week, 1-month, and 2-month postoperative visits but not at the 3-month visit. In the 8-mL, 2-week group, significant differences were found at all postoperative visits. CONCLUSION: This study reveals that MF-impregnated BNDs improve the endoscopic appearance in the healing process of CRSwNP after ESS.

Antifungal activity of osthol in vitro and enhancement in vivo through Eudragit S100 nanocarriers.

In vitro interaction of osthol (Ost) and fluconazole (FLC) was investigated against 11 fluconazole-resistant clinical isolates of Candida albicans. Synergistic activities were determined using the checkerboard microdilution assay. The results of agar diffusion test confirmed the synergistic interaction. We used an enteric material Eudragit S100 for preparation of Ost nanoparticle (Ost-NP) to improve the oral bioavailability, biological activity of Ost. The physicochemical characteristics of Ost-S100-NP revealed Ost-S100-NP with mean particle size of 55.4±0.4 nm, encapsulation efficiency of 98.95±0.06%, drug loading efficiency of 23.89±0.25%, yield of 98.5±0.1% and a polydispersity index (PDI) of 0.165. As the Ost concentration-time curve showed, Ost-S100-NP can increase the plasma concentration and relative bioavailability of Ost compared with Ost-suspension by oral administration. In vivo, Ost-S100-NP enhanced the therapeutic efficacy of Ost against FLC-resistant C. albicans in immunosuppressed candidiasis mice model. The available information strongly suggests that Ost-S100-NP may be used as a promising compound against drug-resistant fungi.

Kaempferol induces autophagic cell death of hepatocellular carcinoma cells via activating AMPK signaling.

In the present study, we demonstrate that Kaempferol inhibited survival and proliferation of established human hepatocellular carcinoma (HCC) cell lines (HepG2, Huh-7, BEL7402, and SMMC) and primary human HCC cells. Kaempferol treatment in HCC cells induced profound AMP-activated protein kinase (AMPK) activation, which led to Ulk1 phosphorylation, mTOR complex 1 inhibition and cell autophagy. Autophagy induction was reflected by Beclin-1/autophagy gene 5 upregulation and p62 degradation as well as light chain 3B (LC3B)-I to LC3B-II conversion and LC3B puncta formation. Inhibition of AMPK, via AMPKα1 shRNA or dominant negative mutation, reversed above signaling changes. AMPK inhibition also largely inhibited Kaempferol-induced cytotoxicity in HCC cells. Autophagy inhibition, by 3-methyaldenine or Beclin-1 shRNA, also protected HCC cells from Kaempferol. Kaempferol downregulated melanoma antigen 6, the AMPK ubiquitin ligase, causing AMPKα1 stabilization and accumulation. We conclude that Kaempferol inhibits human HCC cells via activating AMPK signaling.

Antifungal activity of Rubus chingii extract combined with fluconazole against fluconazole-resistant Candida albicans.

This study aimed to investigate the antifungal activity of Rubus chingii extract in combination with fluconazole (FLC) against FLC-resistant Candida albicans 100 in vitro. A R. chingii extract and FLC-resistant C. albicans fungus suspension were prepared. The minimum inhibitory concentration and fractional inhibitory concentration index of R. chingii extract combined with FLC against C. albicans were determined, after which growth curves for C. albicans treated with R. chingii extract, FLC alone and a combination of these preparations were constructed. Additionally, the mechanisms of drug combination against C. albicans were explored by flow cytometry, gas chromatographic mass spectrometry and drug efflux pump function detection. R. chingii extract combined with FLC showed significant synergy. Flow cytometry suggested that C. albicans cells mainly arrest in G1 and S phases when they have been treated with the drug combination. The drug combination resulted in a marked decrease in the ergosterol content of the cell membrane. Additionally, efflux of Rhodamine 6G decreased with increasing concentrations of R. chingii extract. R. chingii extract combined with FLC has antifungal activity against FLC-resistant C. albicans.

Cases Report the Cronkhite-Canada Syndrome: Improving the Prognosis.

Cronkhite-Canada syndrome (CCS) is a rare nongenetic polyposis syndrome first reported by Cronkhite and Canada in 1955. Up to the present time, the literature consists of ∼400 cases of CCS with the majority being reported from Japan although 49 cases have been described in China.CCS is characterized by diffuse polyposis of the digestive tract in association with ectodermal changes, such as onychomadesis, alopecia, and cutaneous hyperpigmentation. The principal symptoms of CCS are diarrhea, weight loss, abdominal pain, and other gastrointestinal complications, such as protein-losing enteropathy and malnutrition.It has been traditional to consider that CCS is associated with a poor prognosis. This paper describes a relatively mild case and reviews the literature, which more recently, suggests that it may be a more benign condition that might actually be reversible with treatment.There is some evidence that infection or disturbed immunity may be involved in the pathophysiology and that targeting such abnormalities could have therapeutic potential.A strong case could be made for establishing an international case registry for this disease so that the pathophysiology, treatment, and prognosis could become much better understood.

[Treatment of nonalcoholic steatohepatitis by Jianpi Shugan Recipe: a multi-center, randomized, controlled clinical trial].

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicine (CM) intervention in the treatment of nonalcoholic steatohepatitis (NASH) from liver enzyme (ALT), imaging (the liver/spleen CT ratio) and syndrome scores, and to establish standard methods for diagnosis and therapeutic efficacy evaluation with characteristics of CM. METHODS: A multi-center, stratified randomized, parallel controlled, blindness-method evaluated, superiority trial was performed. Totally 204 patients were randomly allocated into two groups, 102 patients in the experimental group (treated with CM) and 102 patients in the control group [treated with Western medicine (WM)]. The alanine aminotransferase (ALT), liver/spleen CT ratio, and clinical symptoms were observed in both groups. RESULTS: Of the randomly allocated 204 cases from 4 hospitals, 3 patients were rejected, and 25 were lost. Totally 176 cases con- formed to the plan with complete follow-ups. After 3 months of treatment, syndrome scores and the improvement of partial clinical symptoms (fatigue and sallow complexion) were superior in the experimental group to those in the control group (P < 0.05). After 3 months of follow-up, the syndrome scores and improvement of partial clinical symptoms (fatigue and sallow complexion) were superior in the experimental group to those in the control group (P < 0.05). There was no statistical difference in improving liver enzymes or the liver/spleen CT ratio between the two groups (P > 0.05). There were 4 adverse reactions/adverse events in the two groups in the process of treatment, mainly covering drug-induced liver injury, diarrhea, and epigastric distension. Adverse reactions had nothing to do with CM treatment. CONCLUSIONS: Jianpi Shugan Recipe had obvious efficacy in treatment of NASH. It could remove the liver fat and play a role in anti-inflammation and liver protection. It also could improve the indices of liver enzymes and the liver/spleen CT ratio effectively, which was superior to Polyene Phosphatidylcholine Capsule (PPC) in improving clinical symptoms, especially for such symptoms as fatigue and sallow complexion.