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Purpose: Supersaturated formulations have been widely explored for improving the oral bioavailability of drugs by using mesoporous silica (MS) to generate supersaturation via molecular adsorption; however, this is followed by precipitation. Several precipitation inhibitors (PI) have been explored to prevent precipitation and maintain the drug in solution for a longer period. However, the combined approach of MS and PIs, the impact of MS and Silica, and the loading of high-molecular-weight neutral molecules such as Cyclosporine A (CsA) have not yet been explored. The present study aimed to explore the impact of MS and a hydroxypropyl methylcellulose (HPMC) matrix on the supersaturation and bioavailability of the neutral drug CsA. Methods: A CsA-loaded mesoporous silica/HPMC ternary matrix and CsA-HPMC and CsA-MS controls were prepared, and physicochemical characterization was carried out. The ternary matrix and controls were investigated for the Non-sink Mini FaSSIF dissolution and biorelevant transfer studies. Furthermore, drug release modeling was performed using DDSolver, and pharmacokinetic studies were performed to assess the impact on oral bioavailability compared with the marketed formulation. Results: The study suggested that the co-loaded CsA, HPMC, and MS demonstrated higher supersaturation than CsA-loaded silica and CsA-HPMC controls. A significant improvement in FaSSIF single medium (2-fold) and biorelevant transfer (3.37-fold) increase in the dissolution profile was observed for the co-loaded CsA-MS-HPMC samples. The in vitro dissolution profile was corroborated by pharmacokinetic studies, which showed a 1.19-fold higher oral bioavailability of CsA-MS-HPMC compared to that of CsA-MS and CsA-HPMC. Conclusion: The pharmacokinetics indicated that CsA-MS-HPMC co-loaded samples demonstrated supersaturation and improved bioavailability compared with the physical mixture. [ABSTRACT FROM AUTHOR]

Vulvovaginitis is a growing concern worldwide because of increasing drug resistance, drug toxicity, low bioavailability, and limitations of topical administration. The purpose of the study was to develop a novel mucoadhesive in situ gel of quercetin–cyclodextrin (CD)-loaded chitosan nanoparticles (NPs) for the treatment of vulvovaginitis. In this work, an innovative association between mucoadhesive (chitosan) and thermosensitive polymers (poloxamer 188 and 407) was used to treat vulvovaginitis. The formulation showed compatible pH (4.08) and a desired rheological behavior (viscosity—158.9 cps at 25.9°C, gelation temperature—37°C, and gelation time—65 s) suitable for vaginal application. The quercetin/sulfobutyl-ether-β-cyclodextrin-loaded chitosan NPs (QCD-NPs), prepared by the ionic-gelation method, showed higher in vitro antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa compared with the quercetin solution because of the ionic interaction between chitosan NPs and bacteria. Moreover, upon incorporating the QCD-NP in in situ gel, the clearance from the vagina might further reduce and longer residence can be achieved at the site of vaginal infection because of sol–gel transition at body temperature. The developed formulation was confirmed to be biocompatible, nonirritant (hen's egg chorioallantoic membrane assay), and bioadhesive (mucoadhesion test) with good antimicrobial efficacy and sustained drug release profile, paving the path for improved therapeutic interventions in the treatment of vulvovaginitis. [ABSTRACT FROM AUTHOR]

In recent years, dyslipidemia, a major risk factor for cardiovascular diseases is on the rise globally due to sedentary lifestyles and unhealthy diets. Though abundant data pertaining to the factors influencing dyslipidemia, the mechanism of action of various drugs and the pathogenesis of the disease are available in the literature, the disease is poorly understood. Animal models play a crucial role in investigating the pathophysiology and aid in developing effective formulations. Despite extensive research being carried out in the arena of dyslipidemia, there is no adequate knowledge about the most suitable in vivo model. A systematic literature search was carried out to review the animal models such as rats, mice, rabbits and zebrafish models with chemical-induced, diet-induced and drug-induced methods that have been used to study dyslipidemia. This review focuses on the mechanism involved in the dyslipidemia induction techniques explored by researchers along with their applications and limitations. The induction methods reported are expected to provide better insight in selecting an appropriate model to draw precise conclusions. [ABSTRACT FROM AUTHOR]

Background: Dandruff caused by Malassezia furfur is a prevailing fungal infection. Although ketoconazole (KTZ) is widely intended for anti‐dandruff treatment, poor solubility, and epidermal permeability limits its use and the marketed KTZ shampoo adversely effects scalp and hair. Objective: To prepare a novel shampoo loaded with KTZ‐coated zinc oxide nanoparticles using green tea extract and evaluate its antifungal activity. Methods: The KTZ‐coated zinc oxide nanoparticles was prepared by green synthesis and was characterized by UV, FTIR, XRD, and the drug entrapment efficiency was investigated. The antifungal activity of the nanoparticles with respect to standard drug, KTZ was tested against Malassezia furfur. Further, a novel antidandruff shampoo was developed by incorporating the prepared nanoparticles into the shampoo base. Results: The formation of KTZ‐coated ZnO nanoparticles was confirmed by UV and FTIR analysis. XRD analysis confirmed the amorphous phase of KTZ in nanoparticles. The drug entrapment efficiency was found to be 91.84%. The prepared nanoparticles showed enhanced activity against Malassezia furfur compared to drug of choice, KTZ (1%). The evaluation of shampoo showed an ideal result. Conclusion: KTZ‐coated ZnO nanoparticles loaded novel shampoo in comparison to marketed anti‐dandruff shampoo could be an effective alternate for the treatment of dandruff. [ABSTRACT FROM AUTHOR]

In drug development, conventional preclinical and clinical testing stages rely on cell cultures and animal experiments, but these methods may fall short of fully representing human biology. To overcome this limitation, the emergence of organ-on-a-chip (OOC) technology has sparked interest as a transformative approach in drug testing research. By closely replicating human organ responses to external signals, OOC devices hold immense potential in revolutionizing drug efficacy and safety predictions. This review focuses on the advancements, applications, and prospects of OOC devices in drug testing. Based on the latest advances in the field of OOC systems and their clinical applications, this review reflects the effectiveness of OOC devices in replacing human volunteers in certain clinical studies. This review underscores the critical role of OOC technology in transforming drug testing methodologies. [ABSTRACT FROM AUTHOR]

Fungal keratitis, an ocular fungal infection, is one of the leading causes of monocular blindness. Natamycin has long been considered the mainstay drug used for treating fungal keratitis and is the only US Food and Drug Administration (USFDA)-approved drug, commercially available as a topical 5% w/v suspension. Furthermore, ocular fungal infection treatment takes a few weeks to months to recover, and the available marketed antifungal suspensions are associated with poor residence time, limited bioavailability (< 5%) and high dosing frequency as well as minor irritation and discomfort. Despite these challenges, natamycin is still the preferred drug choice for treating fungal keratitis, as it has fewer side effects and less ocular toxicity and is more effective against Fusarium species than other antifungal agents. Several novel therapeutic approaches for the topical delivery of natamycin have been reported to overcome the challenges posed by the conventional dosage forms and to improve ocular bioavailability for the efficient management of fungal keratitis. Current progress in the delivery systems uses approaches aimed at improving the corneal residence time, bioavailability and antifungal potency, thereby reducing the dose and dosing frequency of natamycin. In this review, we discuss the various strategies explored to overcome the challenges present in ocular drug delivery of natamycin and improve its bioavailability for ocular therapeutics. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to establish the dose of streptozotocin required to induce Type -1 diabetes in Wistar rats. Background: Streptozotocin is currently employed worldwide to induce insulin-dependent diabetes mellitus also known as Type 1 diabetes mellitus in experimental animals. Though many reports on the use of streptozotocin induction of diabetes are reported in the literature, they were not reproducible. Moreover, there was no mention of the mortality associated with the same as well as the conditions followed during the study. Materials and Methods: In the present study, the dose, route, and solvent used for streptozotocin were investigated. Various doses of streptozotocin 55, 50, 40, and 35mg/kg dissolved in either freshly prepared cold 10mM sodium citrate buffer (pH 4.5) or normal saline solution was administered intraperitoneally as well as intravenously. For intraperitoneal administration, the dose-volume was 10mL/kg whereas for intravenous administration the dose-volume was 2mL/Kg. Different routes were employed to ascertain the cause of mortality for which an autopsy was performed. Besides mortality rate was also determined. Results and Discussion: The findings of the study revealed that a 35-40mg/kg dose of streptozotocin showed less percentage mortality and successful induction of diabetes. Conclusion: Mortality (10-20%) was observed at a dose of 35-40mg/kg streptozotocin. Therefore, streptozotocin (35-40mg/kg) was confirmed to be safe and effective for the induction of diabetes in Wistar rats. This paper highlights subtle intricacies observed during induction of diabetes in Wistar rats using streptozotocin. [ABSTRACT FROM AUTHOR]

Cervical cancer is an aggressive type of cancer affecting women worldwide. Many affected individuals rely on smear tests for the diagnosis, surgery, chemotherapy, or radiation for their treatment. However, due to a broad set of undesired results and side-effects associated with the existing protocols, the search for better diagnostic and therapeutic interventions is a never-ending pursuit. In the purview, the bio-concentration of trace elements (copper, selenium, zinc, iron, arsenic, manganese, and cadmium) is seen to fluctuate during the occurrence of cervical cancer and its progression from pre-cancerous to metastatic nature. Thus, during the occurrence of cervical cancer, the detection of trace elements and their supplementation will prove to be highly advantageous in developing diagnostic tools and therapeutics, respectively. This review provides a detailed overview of cervical cancer, its encouragement by human papillomavirus infections, the mechanism of pathology, and resistance. Majorly, the review emphasizes the less explored role of trace elements, their contribution to the growth and inhibition of cervical cancer. Numerous clinical trials have been listed, thereby providing a comprehensive reference to the exploration of trace elements in the management of cervical cancer. [ABSTRACT FROM AUTHOR]

A novel isocratic stability-indicating chromatographic method was developed, optimized and validated using Design-Expert® following ICH guidelines for the quantification of Timolol maleate (TM). The intrinsic stability of TM was assessed by force degradation studies, which concluded no extensive degradation except under alkaline and oxidative conditions. TM was quantified accurately in the surfactant-based elastic vesicular system by separating it on Hypersil BDS C8 column using triethylamine in H2O (0.15%v/v; pH 3.0) and acetonitrile (ACN; 65:35%v/v). The influence of variable factors like mobile phase pH, injection volume (μL), flow rate (mL/min) and ACN content (%) on method responses were assessed using a full factorial design. The method was linear between 0.05 and 10 μg/mL with an R2 value of 0.9993. Limit of detection and limit of quantification were found to be 0.90 and 27.2 ng/mL. The method was specific, with recovery in plain drug solution of 89–92% and elastic nanovesicles of 90–93%. The experimental model was significant (P  < 0.0001) as indicated by deliberate changes in the method analyzed through analysis of variance. The total drug content in elastic nanovesicles was estimated to be 9.53 ± 0.01 mg/20-mL dispersion and entrapment efficiency was 44.52 ± 0.73%. The developed method was rapid, economic and precise for the quantification of TM in bulk and vesicular system. [ABSTRACT FROM AUTHOR]