Sustained Release In Situ Thermogelling Hydrogel of Cerebrolysin for Treatment of Facial Nerve Axotomy in Rats.

PURPOSE: The most essential principle in managing facial nerve (FN) injury is proper diagnosis and early treatment. This study evaluated local application of different concentrations and injection intervals of Cerebrolysin hydrogel (CBLH) for facial nerve axotomy (FNA) treatment. We hypothesized that local application of CBLH may provide a sustained release of Cerebrolysin and enhance neural regeneration. METHODS: The authors implemented a randomized, controlled, blinded animal study. The sample was composed of the right FN. Functionally, eye-blink reflex was evaluated 2 and 4 weeks postoperatively. All rats were euthanized after 4 weeks, and nerve regeneration was evaluated histopathologically and immunohistochemically (IHC) with antibody against neurofilament (anti-NF) and S100 proteins. Descriptive and correlation statistics were computed, and the P value was set at .05. RESULTS: The sample was composed of 72 adult male rats equally allocated into 8 groups. Groups I and V served as control groups and were injected with phosphate buffered saline once and four times, respectively. Rest of the groups were injected with 5%, 10%, and 15% CBLH once in groups II, III, IV and weekly in groups VI, VII, and VIII. CBLH showed statistically significant FN regeneration by enhancing Schwann and axonal growth compared to control group especially with single injection of 10%, 15%, and 5% 4-time injections, where the P value was less than .001. Significant improvement of eye-blink reflex was correlated with structural improvement associated with CBLH. CONCLUSION: Finally, CBLH enhanced nerve regeneration and rehabilitation after FNA in rats. Therefore, it could be considered as an alternative treatment of FNA. More experimental and clinical trials should be considered to detect the effectiveness of CBLH in neural regeneration.

Gingerol-derivatives: emerging new therapy against human drug-resistant MCF-7.

Cancer chemotherapies have been improved dramatically over the last two decades. In the case of human breast cancer, the combination chemotherapeutic protocol, cyclophosphamide (CPA), doxorubicin (DOX), and 5-fluorouracil (5-FU) (CDF), is often used. Nevertheless, the clinical usefulness of CDF is limited by its remarkably low therapeutic window and frequent eruption of resistance. These limitations prompted our search for a more effective and safe drug candidate that may raise the therapeutic benefits for breast cancer patients. Gingerols' wide therapeutic indices as well as their high efficacy in the suppression of carcinogenesis are well established. However, no thorough study to date has profiled their antibreast cancer activities in depth. Therefore, the aims of the present study are to evaluate the antibreast cancer activities of gingerols in comparison to CDF and to gain insight into the structure activity relationships (SARs) responsible for the observed effect using a breast cancer cell model, MCF-7. Our data revealed that 6-gingerol showed the highest anticancer potency that is superior to that of CDF with IC50 = 30.4 µM. Guided by these results, semisynthetic modifications of 6-gingerol have been carried out to characterize 6-gingerol's SARs. The obtained results showed that the acquisition of free hydroxyl group in the aliphatic side chain of 6-gingerol is essential for the antibreast cancer activity. Likewise, the length of aliphatic side chain in 6-gingerol is optimum for its anticancer activity because any decrease in the side chain length resulted in a dramatic loss of anticancer activity. Additionally, allylation of phenolic group has shown antibreast cancer activity superior to that of 6-gingerol per se. Conversely, methylation or isoprenylation of phenolic group has led to a potential decrease in the anticancer activity, whereas loss of aromaticity resulted in a complete loss of 6-gingerol's cytotoxic activity. Collectively, the present results would simplify drug design to allow safer and more effective antibreast cancer pharmaceuticals to be designed.

Potential combination topical therapy of anal fissure: development, evaluation, and clinical study†.

To treat anal fissure, internal anal sphincterotomy may be associated with surgical risks and incidence of incontinence. Botulinum toxin injection into the anal sphincter is invasive and expensive. Headache and hypotension hindered topical treatment with glyceryl trinitrate. Greater patient compliance, potentiated efficacy, reduced side effects, and lower cost are the major advantages offered by the combination therapy. Therefore, combination topical gels of nifedipine (NIF), lidocaine hydrochloride (LDH) and betamethasone valerate (BMV) were prepared and evaluated regarding viscosity, pH, drug content, and in vitro release. Compatibility study of drug-drug and drug-excipient mixtures preceded the formulation. Stability study was performed. A prospective randomized clinical trial was conducted for six weeks to assess the efficacy of the optimized formula in the treatment of anal fissure either acute (AAF, 37 patients) or chronic (CAF, 34 patients) in comparison with three single drug market products. The compatibility was indicated except in case of LDH with each of poloxamer 407 (P407), methylparaben, and propylparaben as well as BMV with P407. The gels showed acceptable viscosity ranges, tolerated pH values, and drugs content limits complying with the pharmacopeial limit. The gel containing 10% Transcutol® (F2) was selected as optimized formula due to the significant (p < 0.05) enhancement in NIF release. The recommended storage temperature was 8 °C. In comparison with the market products, the optimized gel can be represented as a potential combination therapy of acute and chronic anal fissures as suggested by significantly increased healing% and significantly reduced pain, bleeding, anal discharge and itching without side effects.