Dilip Kumar

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The advent of pH-sensitive liposomes (pHLips) has opened new opportunities for the improved and targeted delivery of antitumor drugs as well as gene therapeutics. Comprising fusogenic dioleylphosphatidylethanolamine (DOPE) and cholesteryl hemisuccinate (CHEMS), these nanosystems harness the acidification in the tumor microenvironment and endosomes to deliver drugs effectively. pH-responsive liposomes that are internalized through endocytosis encounter mildly acidic pH in the endosomes and thereafter fuse or destabilize the endosomal membrane, leading to subsequent cargo release into the cytoplasm. The extracellular tumor matrix also presents a slightly acidic environment that can lead to the enhanced drug release and improved targeting capabilities of the nano-delivery system. Recent studies have shown that folic acid (FA) and iRGD-coated nanocarriers, including pH-sensitive liposomes, can preferentially accumulate and deliver drugs to breast tumors that overexpress folate receptors and αvβ3 and αvβ5 integrins. This study focuses on the development and characterization of 5-Fluorouracil (5-FU)-loaded FA and iRGD surface-modified pHLips (FA-iRGD-5-FU-pHLips). The novelty of this research lies in the dual targeting mechanism utilizing FA and iRGD peptides, combined with the pH-sensitive properties of the liposomes, to enhance selective targeting and uptake by cancer cells and effective drug release in the acidic tumor environment. The prepared liposomes were small, with an average diameter of 152 ± 3.27 nm, uniform, and unilamellar, demonstrating efficient 5-FU encapsulation (93.1 ± 2.58%). Despite surface functionalization, the liposomes maintained their pH sensitivity and a neutral zeta potential, which also conferred stability and reduced aggregation. Effective pH responsiveness was demonstrated by the observation of enhanced drug release at pH 5.5 compared to physiological pH 7.4. (84.47% versus 46.41% release at pH 5.5 versus pH 7.4, respectively, in 72 h). The formulations exhibited stability for six months and were stable when subjected to simulated biological settings. Blood compatibility and cytotoxicity studies on MDA-MB-231 and SK-BR3 breast cancer cell lines revealed an enhanced cytotoxicity of the liposomal formulation that was modified with FA and iRGD compared to free 5-FU and minimal hemolysis. Collectively, these findings support the potential of FA and iRGD surface-camouflaged, pH-sensitive liposomes as a promising drug delivery strategy for breast cancer treatment.

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Human epidermal growth factor receptor-2 (HER2)-positive breast cancer metastasis remains the primary cause of mortality among women globally. Targeted therapies have revolutionized treatment efficacy, with Trastuzumab (Trast), a monoclonal antibody, targeting HER2-positive advanced breast cancer. The tumor-homing peptide iRGD enhances the intratumoral accumulation and penetration of therapeutic agents. Liposomes serve as versatile nanocarriers for both hydrophilic and hydrophobic drugs. Gefitinib (GFB) is a potential anticancer drug against HER2-positive breast cancer, while Lycorine hydrochloride (LCH) is a natural compound with anticancer and anti-inflammatory properties. This study developed TPGS-COOH-coated liposomes co-loaded with GFB and LCH, prepared by the solvent injection method, and surface-functionalized with Trast and iRGD. The dual surface-decorated liposomes (DSDLs) were characterized for their particle size (PS), polydispersity index (PDI), zeta potential (ZP), surface chemistry, surface morphology, and their crystallinity during in-vitro drug release, drug encapsulation, and in-vitro cell line studies on SK-BR-3 and MDA-MB-231 breast cancer cells. The half-maximum inhibitory concentration (IC-50) values of single decorated liposomes (SDLs), iRGD-LP, and Trast-LP, as well as DSDLs (iRGD-Trast-LP) on SK-BR-3 cells, were 6.10 ± 0.42, 4.98 ± 0.36, and 4.34 ± 0.32 μg/mL, respectively. Moreover, the IC-50 values of SDLs and DSDLs on MDA-MB-231 cells were 15.12 ± 0.68, 13.09 ± 0.59, and 11.08 ± 0.48 μg/mL, respectively. Cellular uptake studies using confocal laser scanning microscopy (CLSM) showed that iRGD and Trast functionalization significantly enhanced cellular uptake in both cell lines. The wound-healing assay demonstrated a significant reduction in SDL and DSDL-treated MDA-MB-231 cell migration compared to the control. Additionally, the blood compatibility study showed minimal hemolysis (less than 5% RBC lysis), indicating good biocompatibility and biosafety. Overall, these findings suggest that TPGS-COOH-coated, GFB and LCH co-loaded, dual-ligand (iRGD and Trast) functionalized, multifunctional liposomes could be a promising therapeutic strategy for treating HER2-positive metastatic breast cancer.

This month, on September 29, 2024, as we celebrate World Heart Day, lets dive into the contribution of an age-old and trusted molecule Metoprolol, in the field of cardiology. Just last month, in August 2024, we marked the 46th anniversary of Metoprolol's approval.

Background: Chronic kidney disease (CKD) is a global public health burden with significantly increasing mortality. Chronic kidney disease leads to various complications, including anemia, cardiovascular complications, salt and water retention, metabolic acidosis, electrolyte disorders, and chronic kidney disease-mineral and bone disorder (CKD-MBD), amongst which CKD-MBD is a particularly important complication that develops early.Materials and methods: In the present study, various biochemical analytes were assessed for their significance in monitoring the CKD-MBD in different stages of CKD. Only biochemistry markers were assessed in the present study, as X-rays and other radiological markers give positive results in the very late stages of CKD.Results: The level of intact parathyroid hormone (iPTH) was raised or highly normal from the very early stages of chronic renal failure (CRF), and the differences in progressive stages were highly significant p<0.05. The correlation of iPTH with different biochemistry test parameters of CRF, such as creatinine, estimated glomerular filtration rate (eGFR), vitamin D, calcium, and inorganic phosphate, was also checked to determine its efficacy in the detection of CKD-MBD and, consequently, in preventing the complication of CKD. Parathyroid hormone (PTH) showed a significant positive correlation with creatinine in Stages 4 and 5 (p<0.05 in both stages). It was also observed that with the increase in the PTH level, there was a decrease in the estimated glomerular filtration rate in both Stage 4 and 5 patients.Conclusion: The level of iPTH was significantly increased from Stage 2 onwards; hence, it can be used as a diagnostic marker of CKD-MBD from the initial stages. Subsequent to diagnosis, the progression of CKD-MBD can be prevented by choosing the appropriate intervention from the wide array of treatment options available.

IntroductionAdministering the measles vaccine at an appropriate age and dosage in children is important for India to eliminate measles, a potentially deadly vaccine-preventable disease. Similarly, the Japanese encephalitis (JE) vaccine, particularly in endemic regions is important to prevent morbidity and high-case fatality from the disease. The study attempts to evaluate the coverage of measles and JE vaccines and their predictors.Materials and methodsA mixed method study design, incorporating a three-stage cluster random sampling process was used in the cross-sectional survey conducted among 604 children aged 2-5 years in the Ormanjhi block of Ranchi, Jharkhand, from April 2023 to June 2024. The parents/caregivers of the eligible children were interviewed using a predesigned, pretested semi-structured questionnaire, and the immunization status of children was taken from vaccination cards. A focused group discussion (FGD) and an in-depth interview (IDI) with healthcare providers formed the qualitative component. We conducted descriptive, and logistic regression analysis using the IBM SPSS Statistics for Windows, Version 26 (Released 2019; IBM Corp., Armonk, New York, United States). The association between the coverage of the vaccine and sociodemographic variables was done using the Chi-square test. Logistic regression was used to study the predictors, and a p-value of <0.05 was considered statistically significant.ResultsIn the household survey, the coverage of the measles-containing vaccine first dose (MCV-1) was 594 (98.3%), while the second dose (MCV-2) was 536 (88.7%) out of 604 participants. For the JE vaccine, the coverage of the first dose (JE-1) was 588 (97.4%), while the second dose (JE-2) coverage was 492 (81.5%). In the multivariate logistic regression, religion and the lack of parental knowledge about measles were significant predictors for lower MCV-2 uptake, while the for JE vaccine, religion, father's education, and household head's occupation remained statistically significant factors (p ≤ 0.05). Vaccine hesitancy had mixed perceptions with the child’s unavailability being the most significant reason for hesitancy in both MCV and JE vaccinations. In the FGD, child’s unavailability at times of vaccination and parent’s fear of side effects post vaccination were major factors for missing doses of the vaccine.ConclusionWhile the initial coverage of MCV and JE vaccines is commendable, the substantial drop in the second dose coverage and the delays in administration present significant challenges.

Abstract A 60-day feeding trial was conducted to evaluate the effects of dietary Anabaena blue-green algae (ABGA) meal on the growth

Typesetting math: 100% Department of Applied Science, Aluminium Research Centre REGAL, University of Quebec at Chicoutimi, Chicoutimi, QC G7H 2B1, Canada