Anticancer efficacy of perillyl alcohol-bearing PLGA microparticles

In the present study, a novel poly-lactic glycolic acid (PLGA)-based microparticle formulation of perillyl alcohol (POH) was prepared and characterized. Further, its efficacy was evaluated against di-methyl benzo anthracene-induced skin papilloma in Swiss albino mice. The characterization studies showed that POH-bearing PLGA microparticles were of the size 768 ± 215 nm with a ζ-potential value of −7.56 ± 0.88 mV. The entrapment efficiency of the active drug in particles was 42.4% ± 3.5%. POH-bearing PLGA microparticles were stable and released entrapped drug gradually over an extended time period. The in vitro efficacy of POH-bearing PLGA microparticles was evaluated by examining their differential cytotoxicity and assessing their ability to inhibit epidermoid carcinoma cell line (A253). The POH-based microparticles when administered to tumor-bearing animals caused greater tumor regression and increased survival rate (∼80%) as compared with the group receiving free form of POH (survival rate 40%). The superiority of POH-PLGA microparticles over free form of POH was further evident from their ability to modulate apoptosis-regulating factors

Potential of siRNA-Bearing Subtilosomes in the Treatment of Diethylnitrosamine-Induced Hepatocellular Carcinoma

Therapeutics, based on small interfering RNA (siRNA), have demonstrated tremendous potential for treating cancer. However, issues such as non-specific targeting, premature degradation, and the intrinsic toxicity of the siRNA, have to be solved before they are ready for use in translational medicines. To address these challenges, nanotechnology-based tools might help to shield siRNA and ensure its specific delivery to the target site. Besides playing a crucial role in prostaglandin synthesis, the cyclo-oxygenase-2 (COX-2) enzyme has been reported to mediate carcinogenesis in various types of cancer, including hepatocellular carcinoma (HCC). We encapsulated COX-2-specific siRNA in Bacillus subtilis membrane lipid-based liposomes (subtilosomes) and evaluated their potential in the treatment of diethylnitrosamine (DEN)-induced hepatocellular carcinoma. Our findings suggested that the subtilosome-based formulation was stable, releasing COX-2 siRNA in a sustained manner, and has the potential to abruptly release encapsulated material at acidic pH. The fusogenic property of subtilosomes was revealed by FRET, fluorescence dequenching, content-mixing assay, etc. The subtilosome-based siRNA formulation was successful in inhibiting TNF-α expression in the experimental animals. The apoptosis study indicated that the subtilosomized siRNA inhibits DEN-induced carcinogenesis more effectively than free siRNA. The as-developed formulation also suppressed COX-2 expression, which in turn up-regulated the expression of wild-type p53 and Bax on one hand and down-regulated Bcl-2 expression on the other. The survival data established the increased efficacy of subtilosome-encapsulated COX-2 siRNA against hepatocellular carcinoma

Nanoemulsion Adjuvant Augments Retinaldehyde Dehydrogenase Activity in Dendritic Cells via MyD88 Pathway

Mucosal surfaces are the primary point of entry for many infectious agents and mucosal immune responses serve as the primary defense to these pathogens. In order to mount an effective mucosal immune response, it is important to induce T cell homing to mucosal surfaces. Conventional vaccine adjuvants induce strong systemic immunity but often fail to produce mucosal immunity. We have developed an oil-in-water nanoemulsion (NE) adjuvant that provides mucosal immunity and efficient protection against mucosal pathogens when administered as part of an intranasal vaccine. In the present study, we demonstrate that intranasal immunization with NE indirectly activates the retinaldehyde dehydrogenase (RALDH) activity in dendritic cells through epithelial cell activity leading to SIgA as well as potent cellular responses and expression of α4β7 and CCR9 gut homing receptors on T cells. Confirming these findings, ex-vivo stimulation of splenocytes from NE nasally immunized animals showed increase in Th1/Th17 cytokines while suppressing Th2 responses. In examining mechanisms underlying this activation NE activated RALDH via MyD88 dependent pathways in DCs but did not activate the retinoic acid receptor directly. These results suggest that RALDH immune activities can be achieved by epithelial activation without direct RAR activation, which has significant implications for understanding mucosal immunity and the design of mucosal vaccines

Role of plants in anticancer drug discovery

Cancer is one of the major causes of death and the number of new cases, as well as the number of individuals living with cancer, is expanding continuously. Worldwide the alarming rise in mortality rate due to cancer has fuelled the pursuit for effective anticancer agents to combat this disease. Finding novel and efficient compounds of natural origin has been a major point of concern for research in the pharmaceutical sciences. Plants have been seen to possess the potential to be excellent lead structures and to serve as a basis of promising therapeutic agents for cancer treatment. Many successful anti-cancer drugs currently in use or their analogues are plant derived and many more are under clinical trials. This review aims to highlight the invaluable role that plants have played, and continue to play, in the discovery of anticancer agents.We acknowledge the University of Pretoria for Postdoctoral fellowship to J.K. and B.A.M.http://www.elsevier.com/locate/phytolhb2017ChemistryGenetic

Smart Prosthetic Hand Development using Deep Learning and Inertial Measurement Unit Data

The main contribution of this work is to exhibit an improved developed and evaluation of architectures with higher accuracy for prosthetic hand by deep learning with IMU using 9 degrees of freedom. Deep Learning has been gaining popularity due to its numerous implementations and continuous growing capabilities, including the prosthetics industry which has contributed by developing prosthetic minded by deep learning. Previously conducted research on prosthetic arm that utilizes deep learning with inertial measurement unit (IMU) produced promising results with only using single aspect of the device. This research expanded on that by utilizing accelerometer, gyroscope, and magnetometer. This research study was successfully developed various architectures that yielded promising results with improving on the previous work by achieving 99.2% accuracy

Potential use of liposomal diallyl sulfide in the treatment of experimental murine candidiasis

In the present study, we evaluated the potential of a liposomal formulation of the garlic oil component DAS (diallyl sulfide) in treating disseminated infection caused by the intracellular opportunistic pathogen Candida albicans in experimental mice. The PC (phosphatidylcholine) liposomal formulation of DAS was evaluated for size, ζ-potential, entrapment efficiency and release kinetics, toxicity etc. For therapeutic studies, mice were challenged with intravenous infection dosage of 107 blastospores of C. albicans followed by treatment with various doses of DAS formulations [12 and 6 mg/kg b.w. (body mass)] three times, on alternative days. The antifungal efficacy of liposomal DAS was assessed on the basis of survival of treated mice as well as the residual fungal load in vital organs like liver and spleen of mice. The results of the present study showed that treatment with DAS-bearing liposomes (12 mg/kg b.w.) resulted in the highest survival rate in animals. Liposomal DAS also significantly decreased residual fungal load in vital organs of experimental animals compared with the free form of DAS. The liposomal DAS was also found to be free of toxic manifestations as revealed by the erythrocyte lysis test and liver/kidney function tests. The results of the present study established that the antifungal activity of DAS, a poorly soluble compound, can be enhanced by the incorporation of it into liposomes. Further studies and optimizations are needed to build upon the promising findings of this study to enable the development of an effective plant-derived antifungal formulation that can provide an alternative to currently available antifungal drugs.</jats:p