Folate-conjugated albumin nanoparticles for rheumatoid arthritis-targeted delivery of etoricoxib.

OBJECTIVE: The present study discusses folic acid-etoricoxib-bovine serum albumin nanoparticles (F-ETX-NPs) using folic acid as an over expressed folate receptor ligand for activated macrophages in targeting of rheumatoid arthritis. MATERIALS AND METHODS: For this purpose etoricoxib-loaded BSA nanoparticles (ETX-NPs) were prepared by desolvation method and activated folic acid conjugation with free amine group of BSA was confirmed by FTIR study and zeta potential measurements. RESULTS: The F-ETX-NPs showed spherical in shape with 215.8 ± 3.2 nm average size + 7.8 mV zeta potential, 72 ± 1.3% etoricoxib entrapment efficiency and showed 93.1 ± 2.2% cumulative etoricoxib release upto 72 h. The etoricoxib concentration from F-ETX-NPs was found to be 9.67 ± 0.34 µg/g in inflamed joint after 24 h administration revealed remarkably targeting potential to the activated macrophages cells and keep at a high level during the experiment. DISCUSSION AND CONCLUSION: These results suggest that F-ETX-NPs are potentially vector for activated macrophages cells targeting of rheumatoid arthritis.

Mannosylated solid lipid nanoparticles for lung-targeted delivery of Paclitaxel.

OBJECTIVE: The present study discusses paclitaxel (PTX)-loaded mannosylated-DSPE (Distearoyl-phosphatidyl-ethanolamine) solid lipid nanoparticles (M-SLNs) using mannose as a lectin receptor ligand conjugate for lung cancer targeting and to increase the anticancer activity of PTX against A549 lung's epithelial cancer cells. MATERIALS AND METHODS: The PTX-SLNs were prepared by solvent injection method and mannose was conjugated to the free amine group of stearylamine. The M-SLNs obtained were characterized for their particle size, polydispersity index, zeta potential and morphology by transmission electron microscope. RESULTS: The M-SLNs were spherical in shape with 254 ± 2.3 nm average size, positive zeta potential (3.27 mV), 79.4 ± 1.6 drug entrapment efficiency and showed the lower extent of drug release 40% over 48 h in vitro. Cytotoxicity study on A549 cell lines and biodistrubtion study of drug revealed that M-SLNs deliver a higher concentration of PTX as compared to PTX-SLNs in an alveolar cell site. DISCUSSION AND CONCLUSION: These results suggested that mannosylated M-SLNs are safe and potential vector for lung cancer targeting.

Nanostructured lipid carriers (NLCs): A promising candidate for lung cancer targeting.

Lung cancer stands as the foremost health issue and the principal reason for mortality worldwide. It is projected that India will see over 1.73 million new cases and more than 880,000 deaths related to cancer, with lung cancer being a significant contributor. The efficiency of existing chemotherapy procedures is not optimal because of less soluble nature and short half-life of anticancer substances. More precipitated toxicity and non-existence of targeting propensity can lead to severe side effects, non-compliance, and inconvenience for patients. Nonetheless, the domain of nanomedicine has undergone a revolution in the past few years with the advent of novel drug delivery mechanisms that tackle the drawbacks of conventional approaches. Diverse nanoparticle-based drug delivery methods, including liposomes, nanoparticles, nanostructured lipid carrier and solid lipid nanoparticle that encapsulated chemotherapy drugs, are currently employed for efficient lung cancer therapy. NLCs, recognized as the second-generation lipid nanocarriers, are a focused drug delivery mechanism that has garnered significant interest owing to their multitude of advantages such as increased stability, minimal toxicity, prolonged shelf life, superior encapsulation capability, and biocompatible nature. This review focuses on the NLCs carrier system, discussing its preparation methods, types, characterization, applications, and future prospects in lung cancer treatment.

Current Insights into the Chemistry and Antitubercular Potential of Benzimidazole and Imidazole Derivatives.

Tuberculosis is a disease caused by Mycobacterium tuberculosis (Mtb), affecting millions of people worldwide. The emergence of drug resistance is a major problem in the successful treatment of tuberculosis. Due to the commencement of MDR-TB (multi-drug resistance) and XDR-TB (extensively drug resistance), there is a crucial need for the development of novel anti-tubercular agents with improved characteristics such as low toxicity, enhanced inhibitory activity and short duration of treatment. In this direction, various heterocyclic compounds have been synthesized and screened against Mycobacterium tuberculosis. Among them, benzimidazole and imidazole containing derivatives have been found to have potential anti-tubercular activity. The present review focuses on various imidazole and benzimidazole derivatives (from 2015-2019) with their structure-activity relationships in the treatment of tuberculosis.

Exploring siRNA Umpired Nanogels: A Tale of Barrier Combating Carrier.

Potential short interfering RNAs (siRNA) modulating gene expression have emerged as a novel therapeutic arsenal against a wide range of maladies and disorders containing cancer, viral infections, bacterial ailments and metabolic snags at the molecular level. Nanogel, in the current medicinal era, displayed a comprehensive range of significant drug delivery prospects. Biodegradation, swelling and de-swelling tendency, pHsensitive drug release and thermo-sensitivity are some of the renowned associated benefits of nanogel drug delivery system. Global researches have also showed that nanogel system significantly targets and delivers the biomolecules including DNAs, siRNA, protein, peptides and other biologically active molecules. Biomolecules delivery via nanogel system explored a wide range of pharmaceutical, biomedical engineering and agro-medicinal application. The siRNAs and DNAs delivery plays a vivacious role by addressing the hitches allied with chronic and contemporary therapeutic like generic possession and low constancy. They also incite release kinetics approach from slow-release while mingling to rapid release at the targets will be beneficial as interference RNAs delivery carriers. Therefore, in this research, we focused on the latest improvements in the delivery of siRNA loaded nanogels by enhancing the absorption, stability, sensitivity and combating the hindrances in cellular trafficking and release process.

An exhaustive perspective on structural insights of SGLT2 inhibitors: A novel class of antidiabetic agent.

Diabetes mellitus is the global health issue and become an alarming threat in the modern era where human lifestyle gets compromised with modernization. According to the latest statistical report 2020, USA has 9.47% (31 million among 32.72 cr), China has 8.3% (116.4 million among 139.27 cr) and India has 5.6% (77 million among 135.26 cr) of the diabetic people, indicating that diabetes is more prevailing in developed countries as compared to the developing countries. The number of diabetic patients is rising day by day at a tremendous rate and soon it may affect each and every person in a family. So, there is an urgent need to develop novel entities that can meet the scarcity of present antidiabetic agents. In the last few decades, the sodium-glucose co-transporter 2 (SGLT2) has emerged as a prominent target for the treatment of Type 2 diabetes mellitus due to its novel mechanism of action & no involvement in insulin signaling pathway. Most of the inhibitors that target SGLT2 contain three basic moieties: glucose, two benzene rings (one is connected with glucose and the other with methylene), and the methylene bridge which are similar to dapagliflozin. Several SGLT2 inhibitors and their derivatives such as remogliflozin etabonate (phase-II), sotagliflozin (phase-III) and bexagliflozin (phase-III) are under different phases of clinical trial studies and some have been patented. The present review is focused on SGLT2 inhibitors, structure activity relationships (SARs) of dapagliflozin and its several analogues for their binding affinity with SGLT2. We have also presented and summarized the efforts made by various researchers in terms of the synthesis of various dapagliflozin derivatives till date.

Glycyrrhizin conjugated chitosan nanoparticles for hepatocyte-targeted delivery of lamivudine.

OBJECTIVE: The present study was focused to prepare controlled release glycyrrhizin (GL) conjugated low molecular weight chitosan nanoparticles (CS-NPs) for liver targeting. The hydrophilic antiretroviral drug lamivudine was chosen as a model drug and encapsulated within glycyrrhizin conjugated low molecular weight chitosan nanoparticles (GL-CS-NPs) for liver specificity. METHODS: First, the low molecular weight chitosan (CS) was synthesized through depolymerization method. The low molecular weight chitosan nanoparticles were prepared by inotropic gelation method. Then glycyrrhizin was conjugated with previously prepared low molecular weight chitosan nanoparticles (CS-NPs) and conjugation was confirmed by Fourier transform infrared (FT-IR) spectroscopy. KEY FINDINGS: The prepared GL-CS-NPs were characterized using dynamic light scattering, transmission electron microscopy and FT-IR. The encapsulation efficiency and in-vitro drug release behaviour of drug-loaded GL-CS-NPs were studied using ultra violet spectroscopy and high performance liquid chromatographic methods. Release of lamivudine from the nanoparticles exhibited a biphasic pattern, initial burst release and consequently sustained release. In-vivo biodistribution study suggested the target ability of GL-CS-NPs is better and haematological study shows decline of the tissue damage in comparison with plain drug solution. CONCLUSION: The experimental results show that the glycyrrhizin conjugated LMWC nanoparticles may be used as a potential drug delivery system with hepatocyte-targeting characteristics.