Rice Subsector Development and Farmer Efficiency in Nepal: Implications for Further Transformation and Food Security

With economic development agricultural systems in the Global South transform from subsistence farming to higher productivity with market integration and increase in rural income and food security. In Nepal, agriculture continues to provide livelihoods for two-thirds of the predominantly rural population, largely at a subsistence-level. Rice is the staple food and covers the largest land area but yields are relatively low, with an annual import bill of USD 300 Million. The study uses data from 310 households from two distinct rice producing areas to assess farmers' rice production systems. It analyses farmers' rice production efficiency using a stochastic frontier production function to suggest how to advance the transformation of Nepal's rice sector. Our study finds that while agriculture related services such as access to inputs, information, markets, irrigation, and finance have generally improved, paddy farmers are only able to achieve 76% of potential output. Small/marginal farms were relatively less efficient than medium and large farms. Women farmers faced unequal access to technologies and have lower productivity than men. Unavailability of labor and capital, land fragmentation, and the lack of consistent access to seed and fertilizers contribute to reduced efficiency. Public and private sector investments are needed to enhance the timely and adequate access to quality seeds, fertilizers, processing facilities, and equipment services. Adopting a market systems approach through cooperative farming, targeted delivery of extension services, and linkages with rice millers can promote inclusive growth and improve rice food security in Nepal.

Targeted Delivery of Exosomes Armed with Anti-Cancer Therapeutics

Among extracellular vesicles, exosomes have gained great attention for their role as therapeutic vehicles for delivering various active pharmaceutical ingredients (APIs). Exosomes “armed” with anti-cancer therapeutics possess great potential for an efficient intracellular delivery of anti-cancer APIs and enhanced targetability to tumor cells. Various technologies are being developed to efficiently incorporate anti-cancer APIs such as genetic materials (miRNA, siRNA, mRNA), chemotherapeutics, and proteins into exosomes and to induce targeted delivery to tumor burden by exosomal surface modification. Exosomes can incorporate the desired therapeutic molecules via direct exogenous methods (e.g., electroporation and sonication) or indirect methods by modifying cells to produce “armed” exosomes. The targeted delivery of “armed” exosomes to tumor burden could be accomplished either by “passive” targeting using the natural tropism of exosomes or by “active” targeting via the surface engineering of exosomal membranes. Although anti-cancer exosome therapeutics demonstrated promising results in preclinical studies, success in clinical trials requires thorough validation in terms of chemistry, manufacturing, and control techniques. While exosomes possess multiple advantages over synthetic nanoparticles, challenges remain in increasing the loading efficiency of anti-cancer agents into exosomes, as well as establishing quantitative and qualitative analytical methods for monitoring the delivery of in vivo administered exosomes and exosome-incorporated anti-cancer agents to the tumor parenchyma.

Melittin-Based Nano-Delivery Systems for Cancer Therapy

Melittin (MEL) is a 26-amino acid polypeptide with a variety of pharmacological and toxicological effects, which include strong surface activity on cell lipid membranes, hemolytic activity, and potential anti-tumor properties. However, the clinical application of melittin is restricted due to its severe hemolytic activity. Different nanocarrier systems have been developed to achieve stable loading, side effects shielding, and tumor-targeted delivery, such as liposomes, cationic polymers, lipodisks, etc. In addition, MEL can be modified on nano drugs as a non-selective cytolytic peptide to enhance cellular uptake and endosomal/lysosomal escape. In this review, we discuss recent advances in MEL’s nano-delivery systems and MEL-modified nano drug carriers for cancer therapy.

Precision and Advanced Nano-Phytopharmaceuticals for Therapeutic Applications

Phytopharmaceuticals have been widely used globally since ancient times and acknowledged by healthcare professionals and patients for their superior therapeutic value and fewer side-effects compared to modern medicines. However, phytopharmaceuticals need a scientific and methodical approach to deliver their components and thereby improve patient compliance and treatment adherence. Dose reduction, improved bioavailability, receptor selective binding, and targeted delivery of phytopharmaceuticals can be likely achieved by molding them into specific nano-formulations. In recent decades, nanotechnology-based phytopharmaceuticals have emerged as potential therapeutic candidates for the treatment of various communicable and non-communicable diseases. Nanotechnology combined with phytopharmaceuticals broadens the therapeutic perspective and overcomes problems associated with plant medicine. The current review highlights the therapeutic application of various nano-phytopharmaceuticals in neurological, cardiovascular, pulmonary, and gastro-intestinal disorders. We conclude that nano-phytopharmaceuticals emerge as promising therapeutics for many pathological conditions with good compliance and higher acceptance.

Transdermal Nutraceuticals Delivery System for CNS Disease

Herbal medicines are being used by humans since the oldest civilizations and have been an integral part of traditional and alternative medicines. In recent times, pharmaceutical and biomedical scientists are taking interest in developing nutraceutical-based medicines to overcome the side effects and adverse drug reactions caused by allopathic medicines. Nutraceuticals have started occupying the global market. Nutraceuticals have gained widespread acceptance due to their efficacy in treating difficult to treat diseases, low toxicity, low cost, easy accessibility, etc. Safety and efficacy are other important factors in the commercialization process of nutraceuticals. Different novel advanced drug delivery systems have been constantly studied to improve the efficacy and bioavailability of medicines obtained from herbal sources. The transdermal drug delivery system provides a potent alternative to the conventional method of using nutraceuticals. The development of transdermal system-based nutraceuticals could provide the advantage of enhanced bioavailability, improved solubility, bypass the first-pass metabolism, and targeted delivery of drugs in brain-related disorders. It additionally provides the advantage of being non-invasive. This article reviews the potential effects of various nutraceuticals, in brain-related disorders as well as trends in transdermal nano-systems to deliver such nutraceuticals. We would also focus on advantages, application as well as recent United States-based patents which emphasized emerging interest towards transdermal nutraceuticals in brain disorders.

Theranostic Effect of Folic Acid Functionalized MIL-100(Fe) for Delivery of Prodigiosin and Simultaneous Tracking-Combating Breast Cancer

The metal organic framework (MOF) member, MIL-100(Fe), is considered as attractive drug nanocarrier that may be due to the great porosity, colloidal stability, and biocompatibility. In the present study, the new electrochemical synthesis procedure was presented for MIL-100(Fe) building block, and secondly, folic acid (FA) was introduced to the structure for assessing its potential targeted ability to be entrapped by folic acid-positive breast cancer cells, MCF-7. Several techniques such as SEM, XRD, and FT-IR were used to characterize synthesized nanostructures. Both MIL-100(Fe) and MIL-100(Fe)/FA nanoparticles were between 50 to 200 nm with a slightly positive net charge with an area of 1350 and 831.84 m2/g, respectively. The prodigiosin (PG) is selected as a model drug for MIL-100(Fe) and MIL-100(Fe)/FA-targeted delivery owing to its natural fluorescence and cancer cell selectiveness. The loading capacity of both nanocarrier was around 40% with 93-97% loading efficacy. Moreover, the pH-sensitive prodigiosin release rate of MIL-100(Fe)@PG and MIL-100(Fe)/FA@PG showed that 69 to 73% of the drug was released after 24 hours in an acidic environment with around 20% unwanted leakage. The anticancer potential MIL-100(Fe)/FA cells showed the improvement of selective index (SI) from 3.21 to 12.48 which means that folic acid acts as an effective ligand. The study of cells treated with fluorescence microscopy and flow cytometry analysis reveals the dependence of the receptor on the nanoparticle through endocytosis. Considering the effects of nanoparticles on healthy cells, MIL-100(Fe) and MIL-100(Fe)/FA nanoparticles can be introduced as targeted drug delivery systems for smart targeting breast cancer cells with minimal side effects.