Intratumoral delivery of Mitomycin C using bio-responsive Gellan Gum Nanogel: In-vitro evaluation and enhanced chemotherapeutic efficacy.

Intratumoral drug delivery systems hold immense promise in overcoming the limitations of conventional IV chemotherapy, particularly in enhancing therapeutic efficacy and minimizing systemic side effects. In this study, we introduce a novel redox-responsive intratumoral nanogel system that combines the biocompatibility of natural polysaccharides with the tailored properties of synthetic polymers. The nanogel features a unique cross-linked architecture incorporating redox-sensitive segments, designed to leverage the elevated glutathione levels in the tumor microenvironment for controlled drug release.

COVID-19 retreats and world recovers: A silver lining in the dark cloud.

The coronavirus disease (COVID-19), which the World Health Organization classified as the Sixth Public Health Emergency Of International Concern (PHEIC) on January 30, 2020, is no longer a PHEIC. Millions were affected due to unawareness. The increase in fatalities and shortage of medicine was the first outrage of COVID-19.

Etiopathology, Epidemiology, Diagnosis, and Treatment of Fungal Keratitis.

Fungal keratitis (FK) is a severe ocular condition resulting from corneal infection that is prevalent in tropical countries, particularly in developing regions of Asia and Africa. Factors like corneal lens misuse, inappropriate steroid use, and diagnostic challenges have provoked the epidemic. FK causes significant vision impairment, scarring, and ocular deformities.

Codetermination of antimicrobial agents in rabbit tear fluid using LC-MS/MS assay: Insights into ocular pharmacokinetic study.

Managing ocular microbial infections typically requires pharmacotherapy using antibiotic eye drops, such as moxifloxacin hydrochloride (MFX), combined with an antifungal agent like amphotericin B (AB). We carried out and validated an LC-MS/MS assay to quantify these compounds in rabbit tear fluid in order to look into the pharmacokinetics of these two drugs. We employed a protein precipitation technique for the extraction of drugs under examination.

Toxicity and Its Neuroprotective Effect Against Retinal Ganglion Cell Death Through Modulation of Extracellular Matrix in a Glaucoma Rat Model.

Glaucoma is a complex degenerative optic neuropathy characterized by loss of retinal ganglion cells (RGCs) leading to irreversible vision loss and blindness. has been used for decades in traditional medicine system. However, no extensive studies were reported on its antiglaucoma properties.

Polymers and their engineered analogues for ocular drug delivery: Enhancing therapeutic precision.

Ocular drug delivery is constrained by anatomical and physiological barriers, necessitating innovative solutions for effective therapy. Natural polymers like hyaluronic acid, chitosan, and gelatin, alongside synthetic counterparts such as PLGA and PEG, have gained prominence for their biocompatibility and controlled release profiles. Recent strides in polymer conjugation strategies have enabled targeted delivery through ligand integration, facilitating tissue specificity and cellular uptake.

Pirfenidone: A Promising Drug in Ocular Therapeutics.

Pirfenidone, initially indicated for lung fibrosis, has gone beyond its original purpose, and shown promise in eye care. This detailed review tracks its evolution from lung treatment to aiding eye healing as evidenced by published literature. Pirfenidone's multifaceted attributes extend to mitigating corneal fibrosis, inflammation, and trauma.

Glucagon: Delivery advancements for hypoglycemia management.

As the 100th anniversary of glucagon's discovery approaches, we reflect on the remarkable journey of understanding its pivotal role in glucose regulation. Advancements in glucagon delivery systems for managing hypoglycemia are unfolding with promise, albeit accompanied by formulation and implementation challenges. Recent developments include non-injectable methods like BAQSIMI® (Nasal glucagon) offers a user-friendly option, but stability, bioavailability, and rapid onset remain formulation hurdles.

Trends in Formulation Approaches for Sustained Drug Delivery to the Posterior Segment of the Eye.

The eye, an intricate organ comprising physical and physiological barriers, poses a significant challenge for ophthalmic physicians seeking to treat serious ocular diseases affecting the posterior segment, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Despite extensive efforts, the delivery of therapeutic drugs to the rear part of the eye remains an unresolved issue. This comprehensive review delves into conventional and innovative formulation strategies for drug delivery to the posterior segment of the eye.

Combining donepezil and memantine via mannosylated PLGA nanoparticles for intranasal delivery: Characterization and preclinical studies.

The current work is focused on developing mannose-coated PLGA nanoparticles for delivering Donepezil and Memantine in one dosage form. The formulated nanoparticles were prepared using a simple emulsification technique. The final coated NPs exhibited 179.

Design, synthesis, and biological evaluation of quinoline-piperazine/pyrrolidine derivatives as possible antileishmanial agents.

In pursuance of our efforts to expand the scope of novel antileishmanial entities, a series of thirty-five quinoline-piperazine/pyrrolidine, and other heterocyclic amine derivatives were synthesized via a molecular hybridization approach and examined against intracellular amastigotes of luciferase-expressing Leishmania donovani. The preliminary in vitro screening suggests that twelve compounds in the series exhibited better inhibition against amastigote form with good IC values ranging from 2.09 to 8.

Preclinical pharmacokinetic exploration of a novel osteoporotic quinazolinone-benzopyran-indole hybrid (S019-0385) using LC-MS/MS.

1. The current investigation was to develop and validate the LC-MS/MS method in order to analyse the various pharmacokinetic parameters of S019-0385. A sensitive, selective, and robust LC-MS/MS approach was established and validated for measuring S019-0385 in female mice plasma and tissue, using optimal multiple reaction monitoring (MRM) transition 488.

Recent Insights into the Etiopathogenesis of Diabetic Retinopathy and Its Management.

Diabetic retinopathy (DR) is a microvascular retinal disease associated with chronic diabetes mellitus, characterized by the damage of blood vessels in the eye. It is projected to become the leading cause of blindness, given the increasing burden of the diabetic population worldwide. The diagnosis and management of DR pose significant challenges for physicians because of the involvement of multiple biochemical pathways and the complexity of ocular tissues.

Preclinical Pharmacokinetics and CYP Modulation Activity of Chebulinic Acid: A Potent Molecule Against Metabolic Disease.

Background: Chebulinic acid (CA) is an active constituent of fruits with therapeutic potential against multiple metabolic diseases, including dementia, benign prostate hyperplasia, and osteoporosis.

Objective: The present work intends to explore the preclinical pharmacokinetics, including the absolute bioavailability of CA and its influence on the gene expression of cytochrome P450 enzymes in the liver.

Methods: Quantifying CA and probe drugs samples and preclinical serum samples of male rats were performed using LC-MS/MS.

Ophthalmic nano-bioconjugates: critical challenges and technological advances.

Ophthalmic disease can cause permanent loss of vision and blindness. Easy-to-administer topical and systemic treatments are preferred for treating sight-threatening disorders. Typical ocular anatomy makes topical and systemic ophthalmic drug delivery challenging.

Simultaneous Intranasal Codelivery of Donepezil and Memantine in a Nanocolloidal Carrier: Optimization, Pharmacokinetics, and Pharmacodynamics Studies.

This work focuses on developing nanoemulsions using a low-energy emulsification method for the codelivery of donepezil and memantine in one dosage form intended to be administered via the intranasal route for enhanced brain delivery. The nanoemulsion formulation was prepared using a low emulsification technique and characterized using various microscopy and nasal ciliotoxicity studies. The safe nanoemulsion was intended for preclinical pharmacokinetics with brain distribution and pharmacodynamics in a scopolamine-induced murine model.

LC-MS/MS based quantification of steroidal biomarkers in polycystic ovary syndrome induced rats.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that causes reproductive hormones imbalance, missed periods, infertility and distributed steroidogenesis. Reportedly, during PCOS, the endogenous levels of P4 (Progesterone), 17OHP4 (17-α hydroxy progesterone), and T4 (Testosterone) were significantly altered. Thus, quantification of steroid biomarkers involved in the steroidogenesis pathway of PCOS, such as P4, 17OHP4, and T4, holds significant importance.

Recent Update on Pharmacokinetics and Drug Metabolism in CNS-based Drug Discovery.

Despite significant advancements in CNS research, CNS illnesses are the most important and serious cause of mental disability worldwide. These facts show a tremendous unmet demand for effective CNS medications and pharmacotherapy since it accounts for more hospitalizations and extended care than practically all other disorders combined. The site-targeted kinetics of the brain and, pharmacodynamics of CNS effects are determined/regulated by various mechanisms after the dose, including blood-brain barrier (BBB) transport and many other processes.

Preclinical pharmacokinetics of 4-hydroxy isoleucine using LC-MS/MS: a potential polycystic ovary syndrome phytopharmaceutical therapeutics.

To study the preclinical pharmacokinetics of 4-hydroxy isoleucine (4-HIL) targeted for polycystic ovary syndrome. The quantitative bioanalysis of 4-HIL in different biological matrices in female Sprage-Dawley rats using LC-MS/MS. At 50 mg/kg, 4-HIL had 56.

A QbD-led simple and sensitive RP-UHPLC method for simultaneous determination of moxifloxacin, voriconazole, and pirfenidone: An application to pharmaceutical analysis.

A novel, quick and precise RP-UHPLC analytical method for the simultaneous determination of moxifloxacin (MFX), voriconazole (VCZ) and pirfenidone (PIR) was developed and validated according to the International Conference on Harmonization guidelines using a QbD-driven response surface Box-Behnken design. The developed method was validated considering the selectivity, sensitivity, linearity, accuracy-precision, robustness, stability, limit of detection and limit of quantification, respectively. Resolution between MFX, VCZ and PIR was achieved using a gradient elution protocol against a Waters Symmetry Shield C column (150 × 4.

Simultaneous estimation of voriconazole, moxifloxacin, and pirfenidone in rabbit lacrimal matrix using LC-MS/MS: an application to preclinical ocular pharmacokinetics.

Dynamic emergence of microbial keratitis (MK) requires a promising therapeutic arsenal of antifungal and antibacterial agents like voriconazole (VCZ) and moxifloxacin (MOXI), respectively. Parallelly, another paradigm of MK associated with ulcerative wounds cannot be left unnoticed and requires antifibrotic remedy (pirfenidone, PIR) as an authalic antimicrobial to retain the primordial vision. For designing an effective clinical cure, a combination of these three agents is required at a therapeutic dosage regimen.

Design, synthesis and evaluation of novel pyrrole-hydroxybutenolide hybrids as promising antiplasmodial and anti-inflammatory agents.

In the pursuance of novel scaffolds with promising antiplasmodial and anti-inflammatory activity, a series of twenty-one compounds embraced with most promising penta-substituted pyrrole and biodynamic hydroxybutenolide in single skeleton was designed and synthesized. These pyrrole-hydroxybutenolide hybrids were evaluated against Plasmodium falciparum parasite. Four hybrids 5b, 5d, 5t and 5u exhibited good activity with IC of 0.