Current Drug Delivery - Volume 19, Issue 7, 2022

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) is a highly contagious virus causing COVID-19 disease that severely impacted the world health, education, and economy systems in 2020. The numbers of infection cases and reported deaths are still increasing with no specific treatment identified yet to halt this pandemic. Currently, several proposed treatments are under preclinical and clinical investigations now, alongside the race to vaccinate as many individuals as possible. The genome of SARS-CoV2 shares a similar gene organization as other viruses in the Coronaviridae family. It is a positive-sense, single-stranded RNA. This feature suggests that RNA interference (RNAi) is an attractive prophylactic and therapeutic option for the control of this pandemic and other possible future pandemics of the corona viruses. RNAi utilizes the use of siRNA molecules, which are 21-29 nt duplexes RNA molecules that intervene with targeted gene expression in the cytoplasm by a specific mechanism of complementary destruction of mRNA. Previous experience with SARS-CoV and the Middle East respiratory syndrome (MERS) showed that siRNA molecules were effective against these viruses in vitro and in vivo. Moreover, there have been extensive advances in siRNA technology in the past decade from chemistry and target selection considerations; which concluded with the successful approval of two commercial products based on siRNA technology. In addition, the current knowledge of the genome structure and functionality of the corona viruses enables the recognition of conserved sequences to optimize siRNA targeting and avoid viral escape through mutations, either for the current SARS-CoV2 as well as future corona viruses.

Nanoparticles (NPs) have been widely used in drug delivery systems specifically for chemo-, radio-, photothermal, and photodynamic therapy. Due to the lack of selectivity toward tumor cells, the main target in therapies is to deliver drugs to cancer cells to reduce side effects. Gold nanoparticles (AuNPs) have been described as “promising nanocarriers for therapeutics” due to many properties such as low inherent toxicity, high water solubility, and biocompatibility. Many research groups have focused on taking advantage of two or more therapies simultaneously to have increased efficacy using a lower dosage of the therapeutic drug and reduced multi-drug resistance (MDR). Alternatively, doxorubicin (Dox) modification has been used as a strategy for increased selectivity toward target cells. Over the years, many studies have been performed on NPs to eliminate side effects using polymers, peptides, proteins, DNA, metallic NPs, microgels, and hydrogels on drug carriers. In this review, recent advances of using Dox-AuNPs for chemo-, radio-, photothermal, photodynamic, and combination therapy are briefly discussed, and we also highlight recent progress in the application of Dox-AuNPs for effective cancer therapy.

Introduction: The consumption of large amounts of ethanol can directly lead to acute gastric mucosal bleeding, edema, and erosion, while long-term drinking has been associated with gastric ulcers. Previous research has demonstrated that Har Gabur, a traditional Mongolian medicine, alleviates gastric ulcers through the physical adsorption of its carbon components. It is well known that the immune response has an important role in gastric ulceration. Methods: In the present study, we used an ethanol-induced injury cell and mice model to investigate whether Har Gabur can inhibit the immune response stimulated by ethanol and identify the active constituents of Har Gabur involved in this process. Results: We found that Har Gabur significantly repressed the activated Fas/FasL signal pathway and endogenous Bax/Bcl-2 apoptosis pathway. The molecular mechanism of the protective effect most likely involved the transcription or mRNA stability, as Har Gabur remarkably reversed the change in mRNA level of apoptosis-related genes induced by ethanol. Conclusion: Har Gabur operated in a cell-state-specific manner in vivo without inducing adverse effects in normal mice. Importantly, GO was identified as the main active ingredient of Har Gabur for gastric ulcers.

Background: Fenofibrate (FNB) is a commonly used hypolipidemic agent. However, the oral bioavailability of FNB is limited by slow dissolution due to its low solubility. Thus, investigations on novel FNB formulations are necessary for their use. Objective: The objective of this study is to enhance the oral bioavailability of FNB using optimized Nanostructured Lipid Carrier (NLC) formulations. Methods: Hot homogenization followed by ultrasonication was used to prepare FNB-NLCs. These formulations were optimized using a Box-Behnken design, where the amount of FNB (X1), a ratio of solid lipid/liquid lipid (X2), and the percentage of emulsifier (X3) were set as independent variables, while the particle size (Y1), and Entrapment Efficiency (EE%) (Y2), were used as dependent factors. An in vitro dissolution test was then performed using a paddle method, while an in vivo pharmacokinetic study of FNB-NLC formulation was performed in rats. Results: FNB-NLCs were successfully prepared and optimized using a Box-Behnken design. The particle size and EE% of the FNB-NLC had less than 5% difference from predicted values. The in vitro dissolution and oral bioavailability of the FNB-NLC were both higher than those of raw FNB. Conclusion: A Box-Behnken design was successfully applied to optimize FNB-NLC formulation for the enhancement of the dissolution and bioavailability of FNB, a poorly water-soluble drug.

Background: Asenapine maleate, an anti-schizophrenic drug, is a class II drug with low solubility and high permeability. This exerts a rate-limiting effect on drug bioavailability. Objective: To improve the solubility/dissolution rate of asenapine maleate and hence the bioavailability using the co-crystal approach. Methods: Co-crystals were prepared using the solvent evaporation method. Since the drug has Hbond acceptor count of 6, and H-bond donor count of 2, several co-formers (nicotinamide, urea, succinic, benzoic, and citric acid) were investigated in different ratios. The optimized co-crystals (drug-nicotinamide in a ratio of 1:3) were evaluated using PXRD, DSC, FTIR spectroscopy, and SEM. Additionally, in vitro dissolution and stability studies were conducted. Results: Preparation of the co-crystals was successful except when citric and benzoic acids were used. PXRD patterns showed that the co-crystals were crystalline. FTIR spectroscopy confirmed the formation of H-bond between the drug and the co-former. DSC indicated a lower melting point than that of the components followed immediately by an exothermic peak, which confirmed the formation of co-crystals. SEM showed the formation of crystals with different size and habit. The dissolution of the drug from all the prepared co-crystals was almost similar and much enhanced compared to that of the unprocessed drug. The initial dissolution of the drug from the optimized batch was much faster than that from the other co-crystals and the physical mixture with the same ratio. The optimized batch exhibited long term stability. Conclusion: Co-crystals with improved solubility/dissolution rate of asenapine maleate were prepared successfully and were expected to enhance the bioavailability of the drug.

Introduction: Liquid Semisolid Matrix (LSSM) technology involves the filling of drugmixed gel in hard gelatin capsules for different applications. Methods: In continuation of our previous work on LSSM technology, 10% (w/w) of practically insoluble model drug, mefenamic acid was incorporated in gels of different poloxamers with 8% (w/w) SiO2. Results: Gels exhibited plasticity or pseudoplasticity along thixotropy at 2 and 24 h enabling their easy filling into hard gelatin capsules without content seepage. Mefenamic acid gels prepared with L64 and L92 maintained their apparent viscosities for the study period of one month. Around 100% mefenamic acid was released within 90 min from L64- and in 150 min from L92-SiO2 gels, both with first-order kinetics. In 12 month long-term stability studies, only mefenamic acid-L64- SiO gel at 30°C/65% RH indicated dispersion stability with similar rheology and release pattern to that at 2, 24 and 30 days. No chemical drug-polymer interactions were found in FTIR. Conclusion: The release of practically insoluble mefenamic acid could be enhanced from gel formulated with L64 and SiO2.