Anuradha Gupta

Rheumatoid arthritis (RA) and osteoarthritis (OA) are disabling musculoskeletal disorders that affect joints and cartilage and may lead to bone degeneration. Conventional delivery of anti-arthritic agents is limited due to short intra-articular half-life and toxicities. Innovations in polymer chemistry have led to advancements in hydrogel technology, offering a versatile drug delivery platform exhibiting tissue-like properties with tunable drug loading and high residence time properties This review discusses the advantages and drawbacks of polymeric materials along with their modifications as well as their applications for fabricating hydrogels loaded with therapeutic agents (small molecule drugs, immunotherapeutic agents, and cells). Emphasis is given to the biological potentialities of hydrogel hybrid systems/micro-and nanotechnology-integrated hydrogels as promising tools. Applications for facile tuning of therapeutic drug loading, maintaining long-term release, and consequently improving therapeutic outcome and patient compliance in arthritis are detailed. This review also suggests the advantages, challenges, and future perspectives of hydrogels loaded with anti-arthritic agents with high therapeutic potential that may alter the landscape of currently available arthritis treatment modalities.

Functionalized magnetic nanoparticles have attracted particular interest as potential drug delivery carriers as they offer dual advantage of delivering drugs to target site complemented with magnetic hyperthermia mediated therapy. Hyperbranched polymer-functionalized magnetic nanoparticles have potential to perform dual role of killing cancer cells by hyperthermia (by magnetite core) with apoptosis (by loaded niclosamide). These are formed by co-precipitation of iron salts followed by aminocellulose grafting, branch growth and PEGylation. Nanoparticle formation was investigated by determining particle size, zeta potential and microscopic (TEM, FE-SEM and AFM) studies. Results showed that these nanocarriers were 107 ± 57 nm in size with a zeta potential of –18 mV and exist as nanoparticles. Drug loading and encapsulation efficiency was calculated as 15.28 ± 2.72% and 76.41 ± 1.84%, respectively using UV-Vis analysis. Nanoparticles were internalized into HCT116 cells as investigated using confocal microscopy and flow cytometry. Blank nanoparticles (BNPs) at the dose of 200 µg/mL were found to be cytocompatible using hTERT cells and hemocompatible. Cell viability study suggested that niclosamide-loaded functionalized magnetic nanoparticles (NFMNPs) were more effective (7 times) than free niclosamide in killing colon cancer cells. Moreover, NFMNPs induced apoptosis in immunofluorescence study of cleaved caspase-3. Exposure of NFMNPs to alternating magnetic field (AMF) resulted in slight increase in rate of niclosamide release. AMF exposure drastically reduced cell viability due to dual effects of hyperthermia and niclosamide after treatment with NFMNPs. The potentiation of cell death due to dual effects of hyperthermia and niclosamide was further confirmed by Annexin-V/propidium iodide assay using flow cytometry. The results imply that niclosamide delivery through hyperbranched polymer-functionalized magnetic nanoparticles may serve as an effective strategy for the treatment of colorectal cancer.

The study was conducted to assess the availability of feed sources and nutritional status of Hariana cattle breed during different season in its breeding tract. The structed interview schedule was prepared to collect the information from 240 dairy farmers and the samples of available feed and fodder were collected during different season for proximate analysis. The results revealed that the fodder availibility varies according to season. The available green fodders were maize and jowar during rainy; berseem and oats during winter. The intake of nutrients were compared with requirements of Hariana cattle to find out the nutritional status during different season. The results revealed that the animals were underfed in different seasons. Dry matter intake (DMI) was deficit in all seasons; deficiency of DMI (%) was 21.46, 13.84 and 8.60 during summer, winter and rainy respectively. Total digestible nutrient intake was in excess during rainy and winter season and deficit during summer. Crude protein intake was in excess during winter; deficit in rainy and summer. The intake of Ca and P was less as compared to requirements. The information from the present study might be useful for formulation of balanced ration for Hariana breed of cattle.

Cancer is an evolutionary disease with multiple genetic alterations, accumulated due to chromosomal instability and/or aneuploidy and it sometimes acquires drug-resistant phenotype also. Whole genome sequencing and mutational analysis helped in understanding the differences among persons for predisposition of a disease and its treatment non-responsiveness. Thus, molecular targeted therapies came into existence. Among them, the concept of synthetic lethality have enthralled great attention as it is a pragmatic approach towards exploiting cancer cell specific mutations to specifically kill cancer cells without affecting normal cells and thus enhancing anti-cancer drug therapeutic index. Thus, this approach helped in discovering new therapeutic molecules for development of precision medicine. Nanotechnology helped in delivering these molecules to the target site in an effective concentration thus reducing off target effects of drugs, dose and dosage frequency drugs. Researchers have tried to deliver siRNA targeting synthetic lethal partner for target cancer cell killing by incorporating it in nanoparticles and it has shown efficacy by preventing tumor progression. This review summarizes the brief introduction of synthetic lethality, and synthetic lethal gene interactions, with a major focus on its therapeutic anticancer potential with the application of nanotechnology for development of personalized medicine.