Pharmaceutical Nanotechnology - Volume 8, Issue 2, 2020

Background: Silencing of several genes is critical for cancer therapy. These genes may be apoptotic gene, cell proliferation gene, DNA synthesis gene, etc. The two subunits of Ribonucleotide Reductase (RR), RRM1 and RRM2, are critical for DNA synthesis. Hence, targeting the blockage of DNA synthesis at tumor site can be a smart mode of cancer therapy. Specific targeting of blockage of RRM2 is done effectively by SiRNA. The drawbacks of siRNA delivery in the body include the poor uptake by all kinds of cells, questionable stability under physiological condition, non-target effect and ability to trigger the immune response. These obstacles may be overcome by target delivery of siRNA at the tumor site. This review presents a holistic overview regarding the role of RRM2 in controlling cancer progression. The nanoparticles are more effective due to specific characteristics like cell membrane penetration capacity, less toxicity, etc. RRM2 have been found to be elevated in different types of cancer and identified as the prognostic and predictive marker of the disease. Reductase RRM1 and RRM2 regulate the protein and gene expression of E2F, which is critical for protein expression and progression of cell cycle and cancer. The knockdown of RRM2 leads to apoptosis via Bcl2 in cancer. Both Bcl2 and E2F are critical in the progression of cancer, hence a gene that can affect both in regulating DNA replication is essential for cancer therapy. Aim: The aim of the review is to identify the related gene whose silencing may inhibit cancer progression. Conclusion: In this review, we illuminate the critical link between RRM-E2F, RRM-Bcl2, RRM-HDAC for the therapy of cancer. Altogether, this review presents an overview of all types of SiRNA targeted for cancer therapy with special emphasis on RRM2 for controlling the tumor progression.

Background: Resveratrol is a wonder therapy for the treatment of several skin disorders, including psoriasis, but its skin permeation limits its applications. Objective: The present work dealt with optimizing and formulating resveratrol loaded vitamin E based nanoemulsion and carbomer based nanoemulgel intended for topical application in the treatment of plaque psoriasis. The major objective of this study was to achieve the quality target product profile with respect to enhanced skin permeation and superior skin deposition of the formulated nanoemulgel to achieve the superlative therapeutic advantages. Methods: Formulation by design (FbD) approach was employed to optimize varied critical material attributes such as the concentration of oil and Smix to achieve the desired quality characteristics. Carbomer based nanoemulgel was formulated and evaluated. Results: Optimized formulation was having globule size (168.3 ± 4.98 nm), percentage cumulative permeation (4.81 ± 0.65%), permeation flux (7.62 ± 0.39 μg hr-1cm-2), and skin deposition (668.65 ± 11.98 μg cm-2). Nanoemulgel was found to have optimum physical properties in terms of viscosity, spreadability, pH and physical stability. The extent of skin deposition was approximately 6.682 times higher while the permeation enhancement ratio was around 2.872 as compared to conventional formulation indicating its higher skin targeting abilities, which was further ratified by Confocal Laser Scanning Microscopy results. Conclusion: Nanoemulgel formulated by the current FbD approach has enhanced skin permeation and skin deposition properties as compared to conventional carbomer gel. Thus, it could augment the therapeutic benefits of encapsulated bioactive in the treatment of several skin disorders like psoriasis.

Background: Combination chemotherapy capable of overcoming cancer drug resistance can be facilitated by nanotechnology. Objective: Synthesis, characterization, statistical experimental design, analysis and optimization of stealth pH-sensitive polymeric nanoparticles suitable as a platform for simultaneous delivery of paclitaxel and 17-AAG in breast cancer therapy were investigated. Methods: An acetal crosslinker and a poly(ε)caprolactone macromonomer were synthesized and characterized. The statistical experimental design used was the response surface method (RSM). We used the central composite face-centered design (CCF) in three independent factors and seventeen runs. Nanoparticles were fabricated by dispersion polymerization techniques. Response variables evaluated were: particle size, drug loading, encapsulation efficiency, and in vitro availability. Results: Scanning electron micrographs showed the formation of spherical nanoparticles. Computer software was used for the analysis of variance with a 95% confidence level and Q2 (goodness of prediction) to select an appropriate model for each of the response variables. Each term in each of the models was tested for the significance of the regression coefficients. The computer software optimizer was used for optimization to select factor combination to minimize particle size, time (h) for maximum release of paclitaxel and 17-AAG, to maximize paclitaxel and 17-AAG loading efficiency and to maximize paclitaxel and 17-AAG encapsulation efficiency. Conclusion: The optimization was successful, as shown by the validation data which lie within the confidence intervals of predicted values of the response variables. The selected factor combination is suitable for the in vivo evaluation of the nanoparticles loaded with paclitaxel and 17-AAG.

Background: Bacterial conjunctivitis is a serious ocular infection if left untreated. It is caused by several species of bacteria like Pseudomonas, Staphylococcus and Mycobacterium. Objective: The present investigation explores the development and characterization of moxifloxacin hydrochloride and ketorolac tromethamine combination loaded Eudragit RL 100 nanosuspension for ocular drug delivery in order to overcome the problems associated with conventional dosage forms. Methods: The nanosuspension prepared by nanoprecipitation technique showed successful entrapment of both water-soluble drugs in the polymer matrix indicated by their % entrapment efficiencies. Results: Formulations showed a mean particle size <200 nm with narrow size distribution and positive surface charge due to the presence of quaternary ammonium groups of Eudragit RL100. FTIR study revealed compatibility among the components, while a reduction in the crystallinity of formulation was observed in the PXRD study. The release of both the drugs was found to be sustained in nanosuspension as compared to commercial eyedrops. Ex vivo studies showed increased transcorneal permeation of drugs from nanosuspension, where approximately 2.5-fold and 2-fold increase in the permeation was observed for moxifloxacin hydrochloride and ketorolac tromethamine, respectively. The formulation was stable at 4°C and room temperature. Conclusion: Due to their sustained release, positive surface charge and higher transcorneal permeation, this will be a promising ocular drug delivery.

Background: Zotepine (ZT) is a substituted dibenzothiepine tricyclic molecule and second generation antipsychotic drug. It is available as the parenteral and oral solid dosage form, but, orally administered ZT has a poor oral bioavailability (10%) that might be due to either poor water solubility, high lipophilicity (Log P 4) and also first-pass hepatic metabolism. Objective: The oral bioavailability of ZT was improved by loading into a nanostructured lipid carriers (NLCs) system. Methods: Hot homogenization with probe sonication method was used for the preparation of ZT-NLCs formulations and characterized for an optimal system based on physicochemical characteristics and in vitro release. Differential scanning calorimetry (DSC), X-ray diffraction (XRD) analysis, and scanning electron microscopy (SEM) studies were used to confirm the crystalline nature and shape of the optimized ZT-NLC formulation. The physical stability of the optimized ZT-NLC formulation was evaluated at the refrigerator and room temperature over two months. Furthermore, in vivo pharmacokinetic (PK) studies of optimized ZT-NLC and ZT coarse suspension (ZT-CS) as control formulation, were conducted in male Wistar rats. Results: The optimized formulation of ZT-NLC showed Z-avg, PDI, ZP of 145.8 ± 2.5 nm, 0.18 ± 0.05, -31.6 ± 1.8 mV, respectively. In vitro release studies indicated the sustained release of ZT. DSC and XRD studies revealed the conversion of ZT into an amorphous form. SEM studies showed the spherical shape of the ZT-NLC formulation. PK studies showed 1.8-folds improvement (p<0.05) in oral bioavailability when compared with ZTCS formulation. Conclusion: Overall, the results established that NLCs could be used as a new alternative delivery vehicle for the oral delivery of ZT.