Journal of Pharmaceutical Innovation最新文献

Purpose

This study aimed to develop spanlastics-loaded buccal films to overcome the oral bioavailability limitations of olmesartan medoxomil (OLM), a sparsely water-soluble antihypertensive agent. Methods: OLM-loaded spanlastics were prepared using the ethanol injection method. A 2⁴ factorial design was employed to investigate the effects of different variables on vesicles’ features and to identify the optimized spanlastic formula (OS). Vesicles were characterized in terms of entrapment efficiency (EE), particle size (PS), zeta potential (ZP), and polydispersity index (PDI). OS was further characterized in vitro, incorporated into buccal films, and its pharmacodynamic performance was assessed in a single-dose study in hypertensive rats, compared to orally administered OLM suspension.

Results

OS showed spherical vesicles with EE% of 67.7±2.97%, PS of 202.6±4.38 nm, ZP of ‒32.00±1.27 mV, and PDI of 0.272±0.00. OS showed markedly higher OLM release over 24 h compared to OLM suspension. Differential scanning calorimetry indicated drug amorphization. In vitro characterization, along with histopathological examination, demonstrated that OS-loaded films were well-tolerated and safe for buccal administration. Furthermore, pharmacodynamic evaluation revealed that these films significantly enhanced and sustained the antihypertensive effect of OLM, achieving a 1.68-fold increase in area under the antihypertensive effect-time curve and a 1.67-fold prolongation in effect half-life.

Conclusion

These findings confirm the enhanced and sustained antihypertensive effect of OLM delivered via spanlastics-loaded buccal films, highlighting them as a promising delivery system for OLM.

This research evaluated the phytochemical composition and investigated the protective potential of an ethanol extract of the marine alga Sargassum polycystum against cisplatin-induced hepatotoxicity and nephrotoxicity in albino rats. Gas Chromatography-Mass Spectrometry (GC-MS) analysis of the extract confirmed the presence of key compounds, including 10-bromodecanoic acid ethyl ester, Z- 26-pentatriacontane-2-one, N-hexadecanoic acid, methyl heptadecanoate, nonadecanoic acid ethyl ester, CIS-11-eicosenoic acid. Toxicity was induced by a single intraperitoneal administration of cisplatin (5 mg/kg of body weight) in rat. The intoxicated rats were subsequently treated orally with the S. polycystum extract (250, 350, 450 mg/kg of b.wt) for 30 days. Cisplatin administration significantly elevated serum markers of hepatotoxicity (ALT, AST, ALP, total bilirubin, total cholesterol, and triglycerides) and nephrotoxicity (urea, uric acid, and creatinine). Furthermore, the drug caused a substantial decrease in essential electrolytes (Ca, K, Na, P) and total protein levels, accompanied by notable histological disruption in the liver and kidney tissues. Oral supplementation with the S. polycystum extract dose-dependently ameliorated all observed biochemical disturbances, leading to the normalization of elevated enzyme and renal markers when compared to the cisplatin-control group. Histopathological examination also confirmed that the extract restored the structural integrity of the liver and kidney tissues. Additionally, the extract appeared to enhance the immune status of the affected organs. The findings demonstrate potent hepato- and nephroprotective properties of the Sargassum polycystum ethanol extract against cisplatin-induced damage.

Introduction

Fungal infections are common in tropical regions like India, with Candida albicans being a major causative agent. Ketoconazole, a broad-spectrum antifungal, is commonly used to treat candidiasis but was restricted for oral use by the Food Drug Administration in 2013 due to liver toxicity. However, its topical efficacy is limited by the skin’s barrier, particularly the stratum corneum (SC).

Objective

Formulation, optimization and evaluation of ketoconazole loaded pegylated bilosomal gel for the treatment of topical fungal infection.

Methodology

Pegylated bilosomes were developed via ethanol injection and optimized using Central Composite Design with Brij^® C2, Span^® 60, bile salt, and stirring speed as variables. The optimized pegylated bilosomes were characterized by polydispersity index (PDI), vesicle size, zeta potential (ZP), and entrapment efficiency (%EE). Then the optimized pegylated bilosome was incorporated into Carbopol^® 980NF to form a bilosomal gel, which was evaluated for in vitro release, antifungal activity, stability, ex vivo skin permeation, Confocal Laser Scanning Microscopy (CLSM), in vivo pharmacodynamics, and histopathology studies.

Results

The optimized pegylated bilosomes showed small vesicle size (229.9 nm) with PDI (0.206), ZP (-36.8 mV), & %EE (70.88). Transmission electron microscopy and deformability studies indicated vesicle morphology and elasticity. The 0.3% w/w bilosomal gel achieved 63.60 ± 1.93% in vitro drug release in 8 h and demonstrated enhanced antifungal activity against Candida albicans. Ex vivo studies showed a 2.4-fold increase in skin permeation, and CLSM confirmed deeper epidermal penetration. In vivo, the gel significantly reduced fungal load in infected rats, with histopathology confirming its safety and non-irritancy.

Conclusion

The optimized pegylated bilosomes offer a promising platform for targeted topical antifungal delivery, ensuring improved drug penetration, and site-specific action. This nanocarrier approach can significantly enhance therapeutic outcomes while reducing systemic exposure, establishing a clinically relevant, and good alternative to conventional antifungal formulations.

Objectives

The study aims to investigate the potential of digoxin as an inhibitor of PD-1 through an integrated approach involving in silico methods, NMR NOESY, and in vitro evaluations (MTT assay), followed by the formulation and evaluation of digoxin-loaded glycerosomes for the treatment of skin cancer.

Methods

Initially, we performed molecular docking to determine the binding energy and interaction profile of digoxin with PD-1. Then, NOESY analysis confirmed molecular interactions and hydrogen bonding between digoxin and the target protein. Furthermore, to estimate the cytotoxicity of digoxin, an MTT assay was carried out, resulting in an IC₅₀ value of 2 µM against skin cancer cells (A431). Based on these findings, digoxin-loaded glycerosomes were prepared using the thin film hydration method and optimized with the Box-Behnken Design (BBD). The formulation was assessed for entrapment efficiency (%), in vitro penetration (%), particle size, zeta potential, TEM analysis, stability, and skin penetration using confocal microscopy.

Results

The molecular docking analysis revealed a binding affinity of -7.6 kcal/mol, suggesting a significant interaction between digoxin and PD-1. In NOESY analysis, downfield shifts (0-3 ppm), deshielding of protons, and broadening of peaks indicate that interactions are occurring between the ligand and the protein. The MTT assay revealed significant cytotoxicity with an IC₅₀ of 2 µM. The optimized digoxin-loaded glycerosomes have displayed an entrapment efficiency of 92.93± 2.15%, an in vitro penetration of 85.026± 1.12 %, a particle size of 228.1± 1.27 nm, and a zeta potential of -26.9 mV, highlighting their potential for enhanced skin permeation and drug delivery.

Conclusion

The step-by-step process from computational evaluation to laboratory testing confirmed digoxin’s interaction with PD-1 and cytotoxicity, highlighting its potential to serve as a PD-1 inhibitor. The digoxin-loaded glycerosomes, optimized using the Box–Behnken design, demonstrated enhanced drug entrapment, release, stability, and skin penetration. This makes them a promising transdermal drug delivery system for treating skin cancer.

Purpose

Migraine, a prevalent neurological condition, necessitates innovative treatments beyond existing symptomatic remedies. Drug repurposing presents a fast-track solution, with naloxone identified as a candidate for migraine therapy, despite challenges such as limited blood-brain barrier permeability, short half-life, and extensive hepatic metabolism. However, the therapeutic potential of naloxone can be enhanced through lipid-drug conjugation technique, which improves lipophilicity, optimizes pharmacokinetic parameters, and bypasses hepatic metabolism by facilitating lymphatic targeting when taken orally, allowing extended therapeutic effects.

Methods

The present investigation employed in silico methods to study naloxone and its lipid conjugates, focusing on their modified physicochemical, pharmacokinetic, and pharmacodynamic characteristics. The investigation integrated computational ADMET assessments, therapeutic target forecasting, and molecular docking simulations to validate the interactions of naloxone and its lipid-based derivatives with serotonin, toll-like, and μ-opioid receptors using SwissADME, PKCSM (Deep-PK), Protox, SwissTarget, and SwissDock, respectively.

Results

The results revealed that lipid conjugation significantly modified the physicochemical and pharmacokinetic profiles of naloxone by increasing its half-life, decreasing volume of distribution, altering metabolic profile, and decreasing clearance rate. Target prediction profile of drug and its conjugates revealed its neuroprotective, anti-inflammatory, vasomodulatory, immunomodulatory, analgesic, antidepressant activity. The binding affinity for serotonin, toll-like, and μ-opioid receptors demonstrated its effectiveness for migraine treatment, including pain modulation, neuroinflammation, and serotonergic dysregulation.

Conclusion

In silico predictions suggest that naloxone and its lipid conjugates are promising candidates for migraine treatment. This approach has potential for the design of novel, brain-targeted, and serotonin-modulating compounds for migraine treatment following in vitro and in vivo validation.

This study introduces a novel Acyclovir-loaded cubosomal nanoparticle system incorporated into an in-situ gelling formulation, designed to address the limitations of conventional eye drops in treating herpes keratitis—a leading cause of corneal blindness. Herpes keratitis symptoms, including redness, itching, tearing, and irritation, are driven by inflammatory mediators released from mast cells, eosinophils, and corneal nerves. To combat these, Olopatadine Hydrochloride, a dual-acting H1 antihistamine and mast cell stabilizer, was integrated into the formulation for rapid symptomatic relief. Monoolein was selected as the lipid matrix for cubosome formation, stabilized with Poloxamer 407 using a top-down technique, and embedded in a thermosensitive Gellan gum gel for improved pre-ocular retention and controlled release. The optimized system demonstrated 93.58% Acyclovir and 95.24% Olopatadine release with zero-order kinetics, excellent bioadhesion, isotonicity, and sterility after 14 days of UV sterilization. Stability studies revealed no significant changes in physicochemical parameters, highlighting robustness. The cubosomal in-situ gel significantly enhanced ocular bioavailability and permeability, reduced dosing frequency, minimized systemic side effects, and provided controlled drug release. This innovative approach offers a promising therapeutic solution for herpes keratitis, combining targeted antiviral action with effective anti-inflammatory relief, and represents a major advancement in ocular nanomedicine for improved patient outcomes.

Background

Psychedelic compounds such as ketamine, LSD, psilocybin, and MDMA have emerged as promising therapeutic options for mental health disorders including depression, anxiety, and PTSD. Unlike conventional psychotropic medications, these compounds demonstrate rapid onset and sustained therapeutic benefits, primarily through modulation of serotonin receptor pathways. In recognition of their potential to address significant unmet clinical needs, the U.S. Food and Drug Administration (USFDA) has introduced the Breakthrough Therapy Designation (BTD) to accelerate their clinical development and approval.

Methods

A comprehensive review of clinical trials registered under the BTD was conducted, focusing on psychedelic-assisted psychotherapy for mental health disorders. Data were extracted from public regulatory databases, including ClinicalTrials.gov, and official sponsor announcements. The analysis centred on clinical trial design with respect to USFDA guidelines, sponsoring organisations, therapeutic indications, clinical outcomes, the innovative aspects, legal and the regulatory progression of these compounds.

Results

Major sponsors such as Compass Pathways, MAPS (now Lykos Therapeutics), Usona Institute, Cybin, and Mind Medicine have led pivotal clinical trials under the BTD framework. These studies demonstrated significant reductions in depressive and PTSD symptom severity, along with improved remission rates compared to standard therapies. Psychedelic-assisted therapies exhibited favourable safety profiles and durable efficacy, underscoring their potential to revolutionise psychiatric treatment paradigms. The nose-to-brain innovative formulations, especially nano formulations may take the psychedelics research to the next level.

Conclusion

The USFDA’s BTD has played a transformative role in advancing psychedelic research and facilitating regulatory progress for novel psychiatric therapies. Clinical evidence supports the efficacy and safety of psychedelics as fast-acting treatments for refractory mental health conditions. Continued regulatory and legal support, alongside rigorous long-term studies, will be essential to integrate these therapies into mainstream psychiatric care and optimise patient outcomes. The development of nasal nanoformulations of psychedelics has great future potential in addressing psychiatric-related issues.

Purpose

This study explores the potential of carboxymethyl ethyl cellulose (CMEC) as a carrier for preparing amorphous solid dispersion (ASDs) of itraconazole (ITZ), a poorly water-soluble drug.

Methods

ASDs were prepared via solvent evaporation at drug-to-polymer ratios of 1:1–1:5 and characterized by FTIR, PXRD, and DSC to assess drug–polymer interactions and amorphization. Solubility was evaluated in pH 1.2 and pH 6.8 media, furthermore, in vitro dissolution was studied in both acidic and basic environments. ASD tablets were formulated to assess performance in solid dosage form. Pharmacokinetic studies were conducted in rats, and accelerated stability testing was performed on the optimized formulation.

Results

FTIR confirmed hydrogen bonding between ITZ and CMEC, while PXRD and DSC indicated complete amorphization in optimized ASDs. Solubility and dissolution studies showed negligible release at pH 1.2 but a marked improvement at pH 6.8, with up to 91% release from ASDs versus 4% from pure ITZ. The ASD tablets retained this dissolution advantage, achieving 93% release in basic medium. Pharmacokinetic analysis revealed significantly higher systemic exposure for ITZ: CMEC (1:5), followed by 1:4, compared to pure ITZ. The optimized ASD remained stable under accelerated conditions.

Conclusion

CMEC-based ASDs effectively improved the solubility, dissolution, and bioavailability of ITZ, demonstrating the potential of CMEC as a promising carrier for poorly soluble, weakly basic drugs.

Graphical Abstract

Background

Effective medical logistics are essential to ensure timely supply of consumables and uninterrupted clinical operations. Many hospitals, especially in low-resource settings, rely on manual systems—oral procurement, handwritten orders, and limited delivery staff—leading to stockouts, delays, and increased workload.

Objective

This study assessed the impact of implementing Lean Six Sigma (LSS) integrated with a Supply, Processing, and Distribution (SPD) model on hospital logistics performance in a tertiary hospital in eastern China.

Methods

A before–after design using the DMAIC framework compared pre-implementation (manual) and post-implementation (SPD-LSS) phases. Data were collected from hospital records and a survey of 152 staff. Key indicators included order fulfillment time, monthly stockouts, delivery delays, and manual workload. Paired t-tests and regression analysis were conducted.

Results

After SPD-LSS implementation, order fulfillment time decreased from 63.55 to 61.09 minutes, stockouts from 10.20 to 9.81 per month, delivery delays from 42.89% to 40.86%, and manual workload from 12.61 to 11.53 units. Paired t-tests showed no significant differences (p > 0.05), but regression analysis indicated that reduced fulfillment time significantly predicted lower stockouts (β = 0.209, p = 0.010).

Conclusion

Although overall changes were modest, SPD-LSS integration with smart cabinets, barcoding, and automated alerts reduced manual bottlenecks and improved monitoring. These results suggest a scalable, evidence-based approach for optimizing hospital consumable logistics.