Current Drug Therapy - Online First

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.

Alzheimer's disease (AD) is the world's leading cause of neurological dysfunction, cognitive decline, and neuronal loss in the elderly. The deposition of beta amyloid (Aβ)-containing plaques, and the formation of tau-containing neurofibrillary tangles (NFTs), along with extensive neuroinflammation, are the events that characterize the pathogenesis of AD. The management of this disease remains a significant global challenge, as researchers continuously explore innovative treatment approaches, including the investigation of natural products. Loganin is one of the best-known iridoid glycosides. It is named for the Loganiaceae, having first been isolated from the seeds of a member of that plant family, namely those of Strychnos nux-vomica. It has been reported to have anti-inflammatory effects in various disease models such as Parkinson's disease and acute pancreatitis. Recent investigations have uncovered the preventive effects against Alzheimer's disease and its associated complications. This study focused on the therapeutic potential of loganin in the management of Alzheimer's disease.

The potential molecular target of loganin was identified using the SwissTarget Prediction platform, and the disease target of Alzheimer's disease was identified using the GeneCards database. STRING, Cytoscape, and CB-Dock 2 were used to construct the network pharmacology.

The Venn diagram assisted in shortlisting the top 10 genes from 91 overlapping genes, using Cytoscape, namely ALB, TNF, IL6, EGFR, SRC, IL2, HSP90AA1, MMP2, LGALS3, and REN, which was estimated by the CytoHubba plug-in. The molecular binding score of loganin was determined by using CB-Dock 2 and showed the highest binding energy of -8.7 kcal/mol for the LGALS3 (Galectin-3) protein compared with other proteins.

The integration of in silico network pharmacology with molecular docking thus provides a robust foundation for understanding the multi-target action of loganin, as it regulates the proteins involved in pathways associated with Alzheimer's disease via Galectin-3, supporting the development of natural therapies for the efficient management of Alzheimer's disease.

Combined with a healthy lifestyle, such natural interventions may offer a complementary strategy to help delay or mitigate Alzheimer’s disease progression.

Dragon fruit is a tropical fruit from the cactus family, known for its high nutrient and fiber content. This study investigates the antioxidant potential of red pitaya (Hylocereus polyrhizus), comparing its ethanolic extract with its microencapsulated form using a gelatin-pectin matrix. Red pitaya is rich in betalains, which contribute to its strong antioxidant, anticancer, and antimicrobial properties. However, betalains are unstable and susceptible to degradation under various conditions.

The ethanolic extract of red pitaya was encapsulated through freeze-drying. The resulting nanocapsules were characterized using SEM and FTIR analyses. We also compared the stability of the extract and nanocapsules, total phenol content, and antioxidant activity.

The encapsulation efficiency was approximately 48%. The antioxidant activity of the nanocapsules, with a mean diameter of 0.41 nm, was evaluated using the DPPH assay, which revealed that the nanocapsules exhibited superior antioxidant capacity compared to the ethanolic extract. Although the total phenolic content of nanocapsules was lower than that of the extract, the nanocapsules effectively released phenolic compounds and demonstrated greater stability at high temperatures than the extract.

Encapsulation significantly improved the thermal stability and antioxidant performance of red pitaya extract, demonstrating its effectiveness in preserving sensitive bioactive compounds.

These findings suggest that encapsulation enhances the stability and efficacy of betalains, positioning the nanocapsules as a potential natural additive for functional foods and nutraceuticals.

Acne vulgaris is a dermatological condition that significantly affects the physical appearance and quality of life of patients. The emergence of antibiotic resistance has compromised the therapeutic efficacy of antibiotics in acne management. Burdock is a water-soluble bioactive agent that exhibits antimicrobial, anti-inflammatory, and antioxidant properties.

Burdock was loaded into w/o/w nano-emulsion using the reverse titration method. The globule size, zeta potential, entrapment efficiency, and percentage cumulative drug release of the nano-emulsion were evaluated. The nano-emulsion was incorporated into a Carbopol 940 (0.5%, 1%, and 1.5% w/w) gel, and the drug permeability of the nano-emulsion gel was evaluated. The formulations of the nano-emulsion were optimized using the Box-Behnken design.

The Burdock was loaded into w/o/w nano-emulsion by applying the Quality by Design (QbD) approach considering the effect of the factors (phase volume ratio: PVR, time of primary emulsification: TPE, and concentration of Transcutol P: TLP) on globule size (GS) and % entrapment efficiency (%EE) of the drug.

The optimized nano-emulsion was prepared using Burdock and showed a GS of 176.2 nm and an EE of 99.24% with a PVR of 4.60, a TPE of 3.1 minutes, and a TLP concentration of 8.92%.

The optimized nano-emulsion was transformed into a gel and characterized for morphology, viscosity, pH, drug content, in-vitro release, and ex vivo drug permeation. Finally, skin irritation study and histopathological evaluation suggested that the obtained nano-emulsion gel was effective in the treatment of Acne vulgaris.

Malaria, a life-threatening disease caused by Plasmodium parasites, still poses a severe threat to public health safety in Africa, South America, and Asia. It is transmitted via Anopheles mosquito bites and has been reported to be a major cause of toddler mortalities in these regions. Due to its mutation-mediated drug resistance and continued spread of the disease, there still exists a need to investigate and discover more effective antimalarial drugs. Hydromorphone is a semi-synthetic opioid agonist and a hydrogenated ketone of morphine with pain-relieving qualities and serves as a second-line drug to morphine in the treatment of both chronic and acute pain.

High-throughput virtual screen of hydromorphone analogues was done using Autodock Vina. The results of protein-ligand complexes were visualised using Discovery Studio Visualizer, and ligands with the best binding scores were used to perform MD simulations using GROMACS software.

The promising candidate derivatives included analogues of both hydromorphone and morphine with hydroxy and ether constituents in the benzene ring. The best performing docking scores were carried forward to molecular dynamics using the GROMACS software. The ligands showed stability during these simulations and thus serve as promising inhibitors of DXR.

During molecular docking, all ligands docked in chain A did not bind in the active site. This may be due to the small binding pocket in chain A. For chain B, eight ligands (four with NADPH and without NADPH) with the best docking score were further taken for molecular dynamics simulations, and their RMSDs were calculated after molecular dynamics, which all showed stability in the binding pocket.

The Hydromorphone derivatives explored in this study showed promising results when interacting with chain B of PfDXR (4gae) protein.

Diabetes management is critical for patient health, yet many individuals lack essential knowledge about their condition.

This study aimed to develop and validate a patient information leaflet (PIL) focused on diabetes, assessing its effectiveness in enhancing patient knowledge among individuals with diabetes.

The primary objective was to prepare and validate a patient information leaflet (PIL) on diabetes and evaluate its impact on patient knowledge among diabetic individuals. The secondary objective was to analyze demographic factors, education, family history, and comorbidities influencing baseline knowledge and post-intervention knowledge improvement.

Quasi-experimental pre and post-test design was carried out enrolling 78 inpatients and outpatients diagnosed with T1DM or T2DM. The PIL was developed using evidence-based resources and validated through expert panel reviews. Its readability was evaluated using Flesch Reading Ease (FRE) and Flesch-Kincaid Grade Level (FK-GL) scales, with additional validation through user testing. The leaflet’s design adhered to Baker-Able Leaflet Design (BALD) principles. Pre- and post-intervention knowledge was measured through a structured questionnaire, and participant feedback on the leaflet's content and layout was collected.

The FRE and FK-GL scores for the PIL were 60.3 and 8, respectively. The BALD scores for the English and Kannada versions were 25 and 24, respectively. User testing revealed significant improvements in knowledge, with mean scores increasing from 33.85 ± 23.43 to 93.23 ± 8.58 for the Kannada PIL and from 59.23 ± 24.31 to 93.08 ± 9.47 for the English PIL. A total of 85.9% of participants rated the leaflet as effective in improving their understanding of diabetes management.

The validated PIL significantly enhanced patient knowledge of diabetes. These findings suggest that such educational tools can effectively support patient education in both T1DM and T2DM populations.

Type 2 diabetes mellitus (T2DM) is the leading cause of chronic kidney disease (CKD). Thiamine has shown efficacy in microalbuminuria reduction, but its effect on estimated glomerular filtration rate (eGFR) is still uncertain.

To determine the effect of thiamine on increasing eGFR in patients with T2DM with CKD stage 3.

This RCT was conducted in 35 T2DM with CKD stage 3 patients. 18 received 300 mg thiamine once daily (150 mg/capsule) and 17 received a placebo for 24 weeks. The primary outcome was the difference in the median change in the eGFR with thiamine at 24 weeks. Secondary outcomes included median changes within and between groups in the serum creatinine level, HbA1C level, urinary albumin level, total cholesterol level, LDL level, HDL level, triglyceride level, and adverse events.

The baseline characteristics of the two groups were similar except for body mass index (BMI). After 24 weeks, the median change in eGFR was 1.59 ml/min/1.73 m2 of body-surface area (BSA) in thiamine group as compared to 1.78 ml/min/1.73 m2 of BSA in placebo group, leading to treatment difference of -0.19 ml/min/1.73 m2 of BSA (p = 0.61). The patients who received thiamine had a significant decrease in median HbA1c compared to the placebo (median change difference of -1.35, p < 0.01). The urinary albumin level and all lipid profiles were not significantly different between the two groups. No serious adverse events were reported.

The effects of the two agents on eGFR were not significantly different, but patients who received thiamine had a significant decrease in median HbA1C.

Deprescribing is a physician-led approach to mitigating polypharmacy, particularly among the elderly, to lower adverse events and medication errors. This study explores physicians' attitudes, practices, and barriers to deprescribing.

A cross-sectional survey, framed by existing literature and expert insights, was conducted among 150 physicians to gather data on their experiences with deprescribing, along with associated motivators and barriers. Descriptive statistics and chi-square analyses were utilized to identify factors influencing deprescribing practices.

Weekly deprescribing was practiced by 44% of participants and was associated with the average number of patients seen (p=0.048) and patient age group (p=0.019). Key motivators included cost reduction (70%) and decreased pill burden (66%), while barriers included time constraints (52%) and adherence to prescribing guidelines (50%). Prescribing guidelines (68%) and multidisciplinary approaches (40%) were proposed as suggestions by physicians.

Addressing barriers through structured guidelines, adequate time allocation, and multidisciplinary collaboration could enhance deprescribing practices.

Hypothyroidism causes various disorders in the reproductive system. The use of honey and black seed in traditional medicine is well-established.

possible effects of hydroalcoholic extract of black seed and honey (Dosin) on pituitary-gonadal hormones, spermatogenesis, as well as the level of lipid peroxidation and the expression level of inflammatory and apoptosis genes was determined.

Hypothyroidism was induced with methimazole, and the animals were then divided into four groups: control, hypothyroid, hypothyroid + Dosin 100, and hypothyroid + Dosin 200. Dosin was administered orally for 45 days and serum concentrations of LH, FSH, testosterone and malondialdehyde were measured by ELISA. Sperm analysis was also performed. Histopathological examination was conducted and the expression levels of genes related to apoptosis (Bax, Bad and Bcl-2) and inflammation (IL6, TNFα and IL10) were investigated.

Sperm analysis showed that motility, morphology, and count indices decreased in the hypothyroidism group and significantly improved in the treatment groups (P<0.05). Histological studies showed that the length, diameter and volume of seminiferous tubules, basement membrane thickness, number of Leydig and Sertoli cells and testosterone levels increased in treatment groups (P<0.05). The mean serum levels of LH, FSH and malondialdehyde decreased in treatment groups significantly (P<0.05). Also, the expression of inflammatory genes and Bax and Bad genes decreased in treatment groups while Bcl2 increased (P<0.05). The expression of IL6 and TNFα genes decreased in the treatment groups and IL10 increased significantly (P<0.05).

Dosin probably improves testicular spermatogenesis and strengthens the antioxidant, anti-inflammatory, and anti-apoptotic thyroid systems by regulating pituitary-gonadal hormones.

The study developed a rectal in-situ gel of diazepam using thermosensitive polymer poloxamer 407 (P407). The newer form of in-situ rectal diazepam gel holds great promise in terms of effectiveness and ease of use. This in-situ gel is a remarkable combination of two pharmaceutical forms: a solution and a gel.

The study aims to formulate a rectal in-situ gel of diazepam to improve rectal residence time for treating insomnia, convulsions, and status epilepticus. This innovative approach holds great potential for future application and the study of the effect of the addition of HPMC into the formulation.

Ten formulations with varying concentrations of P407 (14%-19%) and HPMC (0.25%-1%) were prepared and assessed for gelation temperature and time, mucoadhesive force, in-vitro drug release, and FTIR compatibility.

The optimized formula, F5 (18% P407), demonstrated a gelation temperature of 37±3.775°C, gelation time of 341 seconds, mucoadhesive force of 4021 dyne/cm², 100% in-vitro drug release within 8 hours, and 65.23% ex-vivo permeation in 12 hours.

The study concluded that diazepam can be effectively formulated as a thermosensitive in-situ gel for rectal administration. However, the addition of HPMC negatively impacts the physicochemical properties of the gel.

Hypercholesterolemia is one of the main risk factors for cardiovascular diseases and atherosclerosis, which remain the most widespread disease burden worldwide. Statins are the standard procedure for regulating lipid levels, which are recommended as the first medical step to reduce cardiovascular risk; however, many patients present adverse muscle reactions to the treatment. When statin intolerance occurs, other therapies need to be implemented as supportive or substitutive means.

A woman with primary hypercholesterolemia and statin intolerance due to myopathy and headache was treated with 30mg/kg/day of Coriolus Versicolor (L.)Quel. (CV) mushroom extract combined with regular aerobic physical activity and a healthy diet. After 30 days of therapy, the reduction in all lipid profile parameters exceeded 11%. The atherogenic index of plasma AIP decreased from 0.55 to 0.48. Additionally, no adverse reactions to therapy were observed.

Results confirmed the potential of natural products of CV extract in reducing hypercholesterolemia in patients who are intolerant to statins.

A condition associated with neurodegeneration is termed Alzheimer's, characterized by mental as well as memory deterioration. Amyloid beta (Aβ) is a type of peptide that accumulates within the central nervous system and causes plaque, cerebral amyloid angiopathy (CAA), and neurodegeneration (loss of acetylcholine). These peptide forms have a major impact on neuronal damage.

Our goal is to provide an overview of Aβ's potential involvement in developing Alzheimer's condition.

An extensive literature review was done using the standard keywords “amyloid beta”, “amyloid beta precursor protein”, “secretase”, and “Alzheimer’s disease” from the databases SCOPUS, PubMed, Elsevier, and Web of Science.

Amyloid-β precursor protein (AβPP) is converted to Aβ through a series of divisions by β and γ secretases, which are found in lipid rafts. The control of these elements is believed to have a significant role in Aβ production throughout the aetiology of Alzheimer's disease (AD). In conclusion, research on Aβ aggregation and clearance has been active in preventing and curing Alzheimer's disorders. Thus, the purpose of this article was to describe the pharmacological function of Aβ peptide plus its process of aggregation.

Oral, fast-dissolving films are an excellent alternative. The purpose of adopting the solvent casting approach was to create a compelling oral film.

HPMC E15 and sodium alginate polymers were chosen based on their compatibility. The produced films were evaluated in terms of organoleptic characteristics, weight, thickness, folding durability, tensile strength, drug content homogeneity, surface pH, disintegration time, and in-vitro dissolution kinetics.

Among the formulations, F2 had a disintegration time of 14.2 seconds and a phenomenal drug release of 98% in 5 minutes. As a result, formulation F2 emerged as the best option, demonstrating promising qualities for effective drug delivery.

These films are made of thin strips and are easily applied to the tongue or oral mucosal tissue. When they come into contact with saliva, they quickly hydrate and attach, resulting in rapid medicine administration. Fast-dissolving oral films are an excellent alternative for patients who have difficulty swallowing traditional drugs, such as pediatric, geriatric, bedridden, or developmentally impaired people. These films are made of thin strips and are easily applied to the tongue or oral mucosal tissue. When they come into contact with saliva, they quickly hydrate and attach, resulting in rapid medicine administration.

Microneedle technology has emerged as a promising approach for drug delivery, offering advantages such as improved patient compliance and enhanced therapeutic efficacy. This review aims to provide a comprehensive overview of recent advancements in microneedle-based drug delivery systems, emphasizing their potential to overcome limitations associated with traditional transdermal drug delivery methods. The objective is to synthesize existing knowledge, identify key trends, and highlight potential applications of microneedle technology in various medical fields.

A systematic approach was employed to select and analyse relevant studies on microneedle technology. Databases were searched for peer-reviewed articles published and patents or patent applications worldwide within the last decade, focusing on innovations in microneedle materials, design, fabrication techniques, and applications. Studies were evaluated based on their methodology, outcomes, and relevance to current trends in drug delivery. Key data were extracted and synthesized to provide an integrated perspective on the state of microneedle technology.

The review highlights significant progress in microneedle technology; innovations in materials, fabrication techniques, and applications. Advancements include biodegradable microneedles, vaccine drug delivery systems, and integration with biosensors. Innovations led to improved drug bioavailability and reduced side effects. Challenges such as scalability, standardization, and regulatory considerations were also identified.

In conclusion, microneedle technology has evolved significantly, offering a versatile platform for controlled drug delivery and various medical applications. The diversity in design and fabrication methods allows customization for specific therapeutic or diagnostic needs, with numerous patents filed for microneedle innovations, reflecting the intense research and development in this field.