Getting a Handle on Smart Drug Delivery Systems – A Comprehensive View of Therapeutic Targeting Strategies

Smart drug delivery system (SDDS) is a recently emerging therapeutic approach, now turning into a conventional model to deliver drug to specific sites or target. Drug targeted (DT) delivery systems maintain the concentration of the drugs at desirable doses in the body and avoid the need for repeated doses. The DT delivery system have specific distinguishing features such as self-regulated, pre-programmed, multi-targeted, controlled by timely response, monitoring of the targeted drug delivery, responsive to pH, and spatially targeted. The DT delivery system exploits the biological membrane changes in the physiology of malignant cells to increase absorption or entry of drug-coated nanoparticles into targeted tissues. This system delivers a certain quantity of a therapeutic drug for longevity of its action to a targeted area within the human tissue, which in turn enhances efficacy of the treatment by reducing the side effects of drug administration. A new DT therapy strategy is a health improvement technique used in future generations for treatment of genetic diseases and intelligent drug delivery. The ultimate goal of SDDS is to administrate the drugs at the correct time with an exact dose in the body and with efficiency and specificity to the targeted cells that help the patients better adhere to their therapy regimen. The DT system enhances the maintenance of drug levels in targeted tissues and plasma without any destruction to the healthy tissues. This DT delivery system uses various strategies in targeting cells, drug delivery mechanisms, properties of targeted drug, organ-based targeted sites, disease, and drug-targeted vehicles. This chapter deals with all aspects of drug targeting and provides an overview of approaches in drug targeting, drug delivery vehicles, and strategies involved in successful delivery

Hepatocyte nuclear factor Foxa-2 effectively differentiates mesenchymal stem cells to functional hepatocytes

Overexpression of hepatocyte nuclear factor (Foxa-2), a master regulator significantly enhances the hepatic differentiation by triggering targeted liver-specific gene expression for liver development. We investigated the function of key regulators that facilitate hepatic differentiation. The functional hepatocyte was determined by observing morphological changes, expression of liver specific markers through immunocytochemical analysis, qRT-PCR, Western Blot and specific liver function assays. Our study confirmed that induction of functional hepatocyte shows typical epithelial morphology, express hepatic genes and acquire hepatocyte functions. Notably, these cells expressed the markers of mature hepatocytes, including albumin, tyrosine aminotransferase, cytokeratin, Cyp7A1 and hepatic transcription factors. Furthermore, these cells exhibited hepatic functions in vitro, including glycogen storage, albumin production, urea secretion and functional assessment of hepatocytes. We have developed a robust and efficient method to differentiate mesenchymal stem cells into induced functional hepatocytes, which exhibits characteristics of mouse hepatocytes. Apparently, induction of functional hepatocytes will pave a better cellular therapy or effective cell source within a short timeline to facilitate the development of hepatocytes for future clinical applications of regenerative medicine

Hepatocyte nuclear factor Foxa-2 effectively differentiates mesenchymal stem cells to functional hepatocytes

369-380Overexpression of hepatocyte nuclear factor (Foxa-2), a master regulator significantly enhances the hepatic differentiation by triggering targeted liver-specific gene expression for liver development. We investigated the function of key regulators that facilitate hepatic differentiation. The functional hepatocyte was determined by observing morphological changes, expression of liver specific markers through immunocytochemical analysis, qRT-PCR, Western Blot and specific liver function assays. Our study confirmed that induction of functional hepatocyte shows typical epithelial morphology, express hepatic genes and acquire hepatocyte functions. Notably, these cells expressed the markers of mature hepatocytes, including albumin, tyrosine aminotransferase, cytokeratin, Cyp7A1 and hepatic transcription factors. Furthermore, these cells exhibited hepatic functions in vitro, including glycogen storage, albumin production, urea secretion and functional assessment of hepatocytes. We have developed a robust and efficient method to differentiate mesenchymal stem cells into induced functional hepatocytes, which exhibits characteristics of mouse hepatocytes. Apparently, induction of functional hepatocytes will pave a better cellular therapy or effective cell source within a short timeline to facilitate the development of hepatocytes for future clinical applications of regenerative medicine

Medicinal Plants as Therapeutic Alternatives to Combat Mycobacterium tuberculosis : A Comprehensive Review

Tuberculosis (TB) is a serious infectious disease caused by Mycobacterium tuberculosis (MTB) and a significant health concern worldwide. The main threat to the elimination of TB is the development of resistance by MTB to the currently used antibiotics and more extended treatment methods, which is a massive burden on the health care system. As a result, there is an urgent need to identify new, effective therapeutic strategies with fewer adverse effects. The traditional medicines found in South Asia and Africa have a reservoir of medicinal plants and plant-based compounds that are considered another reliable option for human beings to treat various diseases. Abundant research is available for the biotherapeutic potential of naturally occurring compounds in various diseases but has been lagging in the area of TB. Plant-based compounds, or phytoproducts, are being investigated as potential anti-mycobacterial agents by reducing bacterial burden or modulating the immune system, thereby minimizing adverse effects. The efficacy of these phytochemicals has been evaluated through drug delivery using nanoformulations. This review aims to emphasize the value of anti-TB compounds derived from plants and provide a summary of current research on phytochemicals with potential anti-mycobacterial activity against MTB. This article aims to inform readers about the numerous potential herbal treatment options available for combatting TB.publishedVersionPeer reviewe

SMART Drug Based Targeted Delivery: A New Paradigm for Nanomedicine Strategies

Introduction: Targeted drug delivery systems are nanoscale drug carrier molecules designed for improving the communication of cellular and molecular components and biodistribution of tumour targeted drug (chemo) therapeutics. Nanomaterials are generally clusters of molecules, atoms and molecular fragments into extremely small size particles (1-100 nm) in nature. Nanomaterials engineered as self-assembled biodegradable particles were used for targeted drug delivery system. Nanocarriers/ particles should be- capable of transporting high doses of chemotherapeutic drugs/nanomedicines into the targeted tumor cells without disturbing the normal healthy cells. It is also used for construction of novel&nbsp; argeted drug delivery system and future application in nanovaccination and nanotechnology.Conclusion: Multifunctional smart nanoparticles or carries hold out the possibility of effective drug targeted therapeutics in molecular and cellular levels at the earliest stage. Here, we briefly discuss the significance of targeting strategies and drug delivery system and outline the current approaches and future directions in the improvement of tumor targeting nanomedicines.</p

Footprint of the COVID-19 Pandemic in India: A Study of Immune Landscape and Other Factors Shielding Mortality

The impact of the SARS-CoV-2 pandemic has significantly affected global health and created a world crisis. The exponentially increasing numbers of infection and mortality have made preventive measures challenging. India being a highly populated nation has so far effectively counteracted the pandemic outbreak with a significantly lower rate of mortality despite the high infection rates. The genetic architecture of the immune response genes in the Indian population, BCG vaccination, the predominantly young age group of people, and their traditional food habits might contribute to the lower rate of mortality. Human leukocyte antigens (HLA) play a vital role in triggering T cells, and natural killer (NK) cells can immediately react to eliminate infected cells. Activation of virus-specific CD4+ T cells and CD8+ cytotoxic T cells selectively targets the infected cells and strengthens the immunoregulatory system. The checkpoint for NK cell function is the engagement of killer Ig-like receptors (KIR) molecules with their respective HLA ligands overexpressed or expressed on the compromised virus-infected cells which have shown polymorphism among different ethnic groups. Here, we explore if certain KIR-HLA motifs grant Indians a survival advantage in terms of the low rate of mortality. Additionally, enhanced immunity through BCG vaccination may favor fruitful eradication of SARS-CoV-2 and provide the way out as in therapeutic intervention and vaccination strategies

Identification and Characterization of a Newly Isolated Chitinase-Producing Strain Bacillus licheniformis SSCL-10 for Chitin Degradation

Chitinases or chitinolytic enzymes have different applications in the field of medicine, agriculture, and industry. The present study is aimed at developing an effective hyperchitinase-producing mutant strain of novel Bacillus licheniformis. A simple and rapid methodology was used for screening potential chitinolytic microbiota by chemical mutagenesis with ethylmethane sulfonate and irradiation with UV. There were 16 mutant strains exhibiting chitinase activity. Out of the chitinase-producing strains, the strain with maximum chitinase activity was selected, the protein was partially purified by SDS-PAGE, and the strain was identified as Bacillus licheniformis (SSCL-10) with the highest specific activity of 3.4 U/mL. The induced mutation model has been successfully implemented in the mutant EMS-13 (20.2 U/mL) that produces 5-6-fold higher yield of chitinase, whereas the mutant UV-11 (13.3 U/mL) has 3-4-fold greater chitinase activity compared to the wild strain. The partially purified chitinase has a molecular weight of 66 kDa. The wild strain (SSCL-10) was identified as Bacillus licheniformis using 16S rRNA sequence analysis. This study explores the potential applications of hyperchitinase-producing bacteria in recycling and processing chitin wastes from crustaceans and shrimp, thereby adding value to the crustacean industry

An Efficient Protocol for Deriving Liver Stem Cells from Neonatal Mice: Validating Its Differentiation Potential

The success of liver regeneration depends on the availability of suitable cell types and their potential to differentiate into functional hepatocytes. To identify the stem cells which have the ability to differentiate into hepatocytes, we used neonatal liver as source. However, the current protocol for isolating stem cells from liver involves enzymes like collagenase, hyaluronidase exposed for longer duration which limits the success. This results in the keen interest to develop an easy single step enzyme digestion protocol for isolating stem cells from liver for tissue engineering approaches. Thus, the unlimited availability of cell type favors setting up the functional recovery of the damaged liver, ensuring ahead success towards treating liver diseases. We attempted to isolate liver stem derived cells (LDSCs) from mouse neonatal liver using single step minimal exposure to enzyme followed by in vitro culturing. The cells isolated were characterized for stem cell markers and subjected to lineage differentiation. Further, LDSCs were induced to hepatocyte differentiation and validated with hepatocyte markers. Finally, we developed a reproducible, efficient protocol for isolation of LDSCs with functional hepatocytes differentiation potential, which further can be used as in vitro model system for assessing drug toxicity assays in various preclinical trials

Polyester nanomedicines targeting inflammatory signaling pathways for cancer therapy

Funding Information: The work is funded from SRG grant (Grant no. SRG/2022/000395 ) by Science and Engineering Research Board, Department of Science and Technology , Govt. of India. Publisher Copyright: © 2022 The AuthorsThe growth of cancerous cells and their responses towards substantial therapeutics are primarily controlled by inflammations (acute and chronic) and inflammation-associated products, which either endorse or repress tumor progression. Additionally, major signaling pathways, including NF-κB, STAT3, inflammation-causing factors (cytokines, TNF-α, chemokines), and growth-regulating factors (VEGF, TGF-β), are vital regulators responsible for the instigation and resolution of inflammations. Moreover, the conventional chemotherapeutics have exhibited diverse limitations, including poor pharmacokinetics, unfavorable chemical properties, poor targetability to the disease-specific disease leading to toxicity; thus, their applications are restricted in inflammation-mediated cancer therapy. Furthermore, nanotechnology has demonstrated potential benefits over conventional chemotherapeutics, such as it protected the incorporated drug/bioactive moiety from enzymatic degradation within the systemic circulation, improving thephysicochemical properties of poorly aqueous soluble chemotherapeutic agents, and enhancing their targetability in specified carcinogenic cells rather than accumulating in the healthy cells, leading reduced cytotoxicity. Among diverse nanomaterials, polyester-based nanoparticulate delivery systems have been extensively used to target various inflammation-mediated cancers. This review summarizes the therapeutic potentials of various polyester nanomaterials (PLGA, PCL, PLA, PHA, and others)-based delivery systems targeting multiple signaling pathways related to inflammation-mediated cancer.Peer reviewe