Current Drug Therapy - Online First

Glaucoma is a common eye condition characterized by elevated intraocular pressure (IOP), which can lead to gradual vision loss or serious ocular issues. An effective dosage form is needed to address challenges, such as poor bioavailability and short retention time on the ocular surface. The current study aims to develop a sustained-release in-situ gel formulation by modifying its polymeric composition, thereby overcoming the barriers of existing ocular drug delivery systems.

The formulations were prepared using the cold method and optimized with experimental design software to assess the effect of different concentrations, with viscosity as the dependent variable. The optimized formulation (S2) was tested for clarity, viscosity, pH, gelling capacity, rheological behavior, and drug–polymer interactions in-vitro, ex-vivo, and in-vivo.

The in-situ gel was transparent, with a pH of 7.1, viscosity of 16327 CP, and transformed from sol to gel at ocular pH. Additionally, the formulation demonstrated sustained drug release in both in vitro and in vivo studies, yielding a favorable result in reducing IOP.

Among all the polymers used in the formulation, Aristoflex and sodium alginate make an excellent formulation with a more extended gelling period and increased ocular residence.

The optimized formulation (S2), unlike traditional eye drops, may offer improved ocular delivery at lower doses and enhance patient compliance.

The Defined Daily Dose (DDD) is a statistical metric for quantifying drug utilization that does not always align with the Prescribed Daily Dose (PDD). This study aimed to identify the discrepancies between prescribed daily dose (PDD) and defined daily dose (DDD) among congestive heart failure (CHF) patients.

A single-center, prospective observational study was conducted among patients with heart failure at the outpatient Cardiology Department over a period of three months. All eligible prescriptions containing guideline-directed medical therapy (GDMT) were included, irrespective of the patient’s sex, and for those aged ≥18 years with New York Heart Association (NYHA) class I–III heart failure. Standard definitions of DDD and PDD were employed. A drug registry was curated on an ad hoc basis that encompassed all relevant patient and medication data, from which DDD and PDD were computed.

A total of 84 eligible patients [63 (75%) males and 21 (25%) females] with a mean age of 60.08 ± 10.11 years were recruited to the study with consent. The majority (94%) were diagnosed with heart failure with reduced ejection fraction (HFrEF), 44% were de novo, and 48% belonged to NYHA class III. A total of 685 medicines were used among participants, with an average of 8.2 (mean 10.54). However, only 37% of medicines were from GDMT, where the most commonly prescribed drugs per patient were β-blockers (89%; n = 253), followed by 68% of SGLT2 inhibitors, 67% of ARNI, and 50% of MRA. The average PDD: DDD ratio for four-pillar therapy ranged from 0.23 (β-Blockers) to 0.33 (MRA) and 1 (SGLT2-i). Except for GDMT, the PDD was 0.06 DDD for Enoxaparin, 1.14 DDD for Glimepiride, and 2.0 DDD for Rosuvastatin.

The PDDs were lower than the DDDs for most of the prescribed drugs. These discrepancies do not necessarily relate to real-time patient characteristics.

The variability of PDD and DDD for most drugs suggests the need for further monitoring to optimize patient care.

Therapeutic anticoagulation is essential for the prevention and treatment of both venous and arterial thromboembolic events. This study aims to present clinically relevant evidence on the use of enoxaparin (also known as Lovenox or Clexane) in various conditions, including stroke and atrial fibrillation.

This focused literature review was conducted using keywords relevant to the research topic in PubMed, Scopus, and Web of Science. The reference lists of eligible articles published up to April 29th, 2025, were also screened to identify additional studies of relevance to the aims of the investigation. Comprehensive, methodologically appropriate, well-informed, and high-quality articles were selected for inclusion (n = 102).

Enoxaparin is an anticoagulant that inhibits clot formation by enhancing antithrombin-mediated inactivation of factor Xa (and, to a lesser extent, factor IIa), but its use is associated with an increased risk of bleeding. Factor XI plays a minimal role in physiological hemostasis but contributes substantially to thrombus propagation, making it an appealing therapeutic target for reducing bleeding risk while maintaining antithrombotic efficacy. To achieve the desired therapeutic effect, individualized dosing strategies may be required, particularly in women, who may have different pharmacokinetic responses compared with men. The standard treatment dose of enoxaparin is 1 mg/kg administered every 12 hours for the prevention and treatment of thromboembolic events in various clinical conditions. Dose adjustments may be necessary in patients with impaired kidney function, whereas individuals with obesity often require standard or higher, not lower, weight-based doses to achieve therapeutic anti-Xa levels.

Early initiation of direct oral anticoagulants (DOACs) after ischemic stroke has been shown to reduce the risk of recurrent thromboembolic events and vascular death within the first 30 days in appropriately selected patients. Enoxaparin should be used cautiously with nonsteroidal anti-inflammatory drugs (NSAIDs), such as naproxen, ibuprofen, or aspirin, because these agents impair platelet function and increase the risk of bleeding. In addition, antiplatelet medications, including prasugrel, ticagrelor, and clopidogrel, as well as certain herbal supplements, such as ginkgo biloba, fish oil, garlic, ginseng, and ginger, may further inhibit platelet function and heighten bleeding risk.

To evaluate efficiency and hemorrhage risk, anti-Xa agents may serve as a therapeutic option in populations treated with enoxaparin for thromboembolic disorders. Hemorrhagic bullous dermatosis, hepatotoxicity, loss of control or numbness, hypoaldosteronism, osteoporosis, and thrombocytopenia are some are some reported side effects of enoxaparin. A considerably lower dose of enoxaparin should be prescribed in women due to sex differences when compared to men.

Schizophrenia is a typical psychotic disorder, also known as a split mind disorder, characterized by symptoms like delusions, hallucinations, and lack of insight. Chlorpromazine HCl is an antipsychotic medication commonly used to treat schizophrenia. The drug has an extensive hepatic first-pass metabolism and poor bioavailability. In addition, it is poorly permeable, resulting from its hydrophilicity.

A niosomal in-situ nasal gel loaded with chlorpromazine HCl was developed for brain delivery in the current study. The thin-film hydration method was used to formulate noisome, 3² randomized full factorial design was used for optimization. They were evaluated for in-vitro drug release, zeta potential, EE%, particle size, and shape and morphology. To create an in-situ gel, these noisome were subsequently incorporated into a Carbopol-934P and HPMC-K4M liquid gelling solution.

The vesicle size ranged from 111.3 nm to 171.4 nm, with the optimized F5 batch having a zeta potential of -32.0 mV. Entrapment efficiency ranged from 74.71% to 91.78%, and cumulative percent release ranged from 83.83% to 95.61%. Ex-vivo studies showed 93.74% drug permeation through sheep nasal mucosa after 8 hours.

The nasal niosomal in-situ gel of chlorpromazine HCl offers a promising approach for targeted brain delivery in schizophrenia, improving drug retention and patient compliance. Its potential for rapid relief makes it suitable for patients with poor oral absorption or compliance, and may help reduce hospital admissions during acute episodes.

This research demonstrated that niosomes have the potential for intranasal delivery of Chlorpromazine HCl, offering advantages over conventional formulations.

Zearalenone (ZEN) is an estrogenic mycotoxin produced by a specific species of Fusarium fungus. This experimental animal study investigated the antioxidant effects of Lactobacillus acidophilus on oxidative stress caused by ZEA in the ovarian and uterine tissues of an animal model.

This experimental animal study was conducted on 40 female mice randomly divided into four groups (n=10). The groups received normal saline, ZEN (40 μg/kg/day, IP), L. acidophilus [5×10^9 CFU/ml, intraperitoneally (IP)], or a combination of ZEN and L. acidophilus for one week. At the end of the intervention, blood samples were collected under deep anesthesia, and the uterine and ovarian tissues were isolated. Biochemical markers (MDA, TAC, thiol groups, sex hormones) and histological changes were evaluated. GraphPad Prism 5 was used for statistical analysis.

ZEN significantly reduced total antioxidant capacity (TAC) and thiol levels while increasing malondialdehyde (MDA) in ovarian and uterine tissues (p<0.0001), indicating heightened oxidative stress and disrupted hormonal balance by elevating progesterone and lowering estrogen levels (p < 0.0001). L. acidophilus treatment mitigated these effects, partially restoring TAC, thiol, and hormone levels (p < 0.01) while reducing MDA (p < 0.01). Histopathologically, ZEN caused a reduction in follicle count in the ovaries, which was significantly alleviated by L. acidophilus co-treatment.

The findings highlighted the significant protective role of Lactobacillus acidophilus against ZEN-induced oxidative stress and endocrine disruption in the murine reproductive system. ZEN markedly impaired antioxidant defenses (reduced TAC and thiol levels, elevated MDA) and altered sex hormone profiles (increased progesterone, decreased estrogen), consistent with its known estrogenic and pro-oxidant effects. These adverse outcomes were accompanied by notable histopathological damage in ovarian and uterine tissues. L. acidophilus supplementation effectively attenuated these effects, likely through multiple mechanisms: direct free radical scavenging, activation of the Nrf2-mediated antioxidant pathway, physical binding and detoxification of ZEN, anti-inflammatory actions, and modulation of the gut-reproductive axis via short-chain fatty acids.

The present study has demonstrated L. acidophilus to exert significant protective effects against ZEN-induced oxidative stress, hormonal disruptions, and tissue damage in the ovary. Thus, probiotic supplementation may serve as an effective strategy to mitigate the adverse effects of ZEN exposure on reproductive health; however, further studies are warranted.

This review explores the advancements in drug delivery systems using microspheres, developed to overcome the limitations of traditional drug administration methods. Microspheres are engineered to deliver therapeutic agents to specific sites with controlled release, thereby improving treatment efficacy and reducing systemic side effects.

A comprehensive literature search was conducted using PubMed, Science Direct, Google Scholar, Bentham Science, Elsevier, Springer Nature, ResearchGate, Wikipedia, Frontiers, and Scribd. The search included English-language articles published between 2010 and 2025 using keywords such as “microspheres,” “drug delivery,” “controlled release,” “biodegradable polymers,” “encapsulation,” “targeted delivery,” “vildagliptin microspheres,” and “fenugreek extract delivery.” A total of 119 articles were screened, and studies were selected based on their relevance to microsphere formulation techniques, polymer characteristics, drug release mechanisms, and their applications.

Microspheres are being utilised as vehicles for transporting medicinal substances to particular locations in controlled release systems. They are made up of synthetic polymers or proteins that degrade naturally. By combining the advantages of floating and high adhesiveness, microspheres can enhance the absorption into the bloodstream and regulate the release of medications, limiting dose regularity and improving conformity among patients. Using microspheres as a depot mechanism allows parenteral formulations to be administered under controlled conditions.

The utilisation of microspheres represents a significant advancement in drug delivery technology. Their ability to improve drug stability, bioavailability, and patient compliance has been well-documented. However, challenges such as manufacturing scalability and consistency remain key obstacles to widespread clinical adoption.

Microspheres have sparked great curiosity about their ability to target various diseases. In the future, microspheres will be crucial for innovative medicine delivery by merging several methods, particularly in the domains of genetic data and mutations, pathological cell categorisation, diagnosis, reliable, effective, and targeted in vivo delivery, and additives that serve as microscopic models of the human body's damaged tissues and organs.