Journal of Pharmaceutical Innovation最新文献

Purpose

Diabetic nephropathy (DN), complication of diabetes, is caused by persistent hyperglycemia leading to oxidative stress and inflammation in renal tissues. Carvacrol, natural phenolic compound, shows protective effects but has issues with solubility and bioavailability. The current study aimed to prepare and characterize carvacrol loaded cubosomes to improve delivery and therapeutic efficacy on HFD-STZ induced diabetic nephropathy in rats.

Methods

Carvacrol- loaded cubosomes were prepared and optimized using Box-Behnken Design and compatibility of the drugs and the excipients were established by using various analytical techniques. The optimized formulation (Batch F16) exhibited an entrapment efficiency of 92%, nano-sized particles (265.1 nm), a polydispersity index of 0.281, and a stable zeta potential of -16.7 mV was selected for Ex-vivo (intestinal permeability) and In vivo (HFD-STZ induced diabetes in rats) studies.

Result

Ex-vivo permeability showed greater intestinal absorption of carvacrol- loaded cubosomes as compared to carvacrol. In vivo, carvacrol- loaded cubosomes substantially improved body weight, glucose levels, lipid profile and renal function markers such as BUN, creatinine, albumin and urine albumin, creatinine. Carvacrol cubosomes raised levels of antioxidants and lowered lipid peroxidation and TNF- α in kidney homogenates. Molecular docking results were also supported a high affinity of carvacrol toward some important proteins related to glucose metabolism, lipid metabolism and oxidative stress.

Conclusion

The results indicated that carvacrol- loaded cubosomes possessed strong nephroprotective, antioxidant, and anti-inflammatory effects than plain carvacrol and therefore, can act as a new therapy in the treatment of diabetic nephropathy.

Background

Medicinal plants are good sources of secondary metabolites, which are important in disease control and drug development.

Objectives

The present study aimed to investigate the phytochemical composition and antimicrobial potential of Glinus lotoides L. leaf ethanolic extracts.

Results

Qualitative phytochemical screening revealed the presence of carbohydrates, alkaloids, tannins, glycosides, phenols, steroids, flavonoids, saponins, and terpenoids, while oils, resins, amino acids, and quinones were absent. GC-MS analysis of the ethanolic extract identified 16 bioactive compounds, with 9,12-Octadecadienoic acid (Z, Z)- (36.31%) as the most abundant, while the chloroform fraction was dominated by Bis(2-ethylhexyl) phthalate (90.16%). Antibacterial assays demonstrated significant activity, with the ethyl acetate fraction exhibiting the highest zones of inhibition (ZOI) against R. solanacearum (18.5 mm) and X. axonopodis (19.5 mm). The chloroform fraction showed potent antifungal activity against F. oxysporum and A. niger (ZOI: 18 mm each). Anti-biofilm assays revealed strong inhibition by chloroform extract against R. solanacearum (SBF: 1.035) and ethyl acetate against X. axonopodis (SBF: 0.848). Additionally, the chloroform fraction displayed broad-spectrum anti-pellicle activity, inhibiting all tested bacterial and fungal strains.

Conclusion

These findings highlight G. lotoides as a promising source of antimicrobial and anti-biofilm agents, warranting further exploration of its bioactive compounds for pharmaceutical applications.

Bromocriptine mesylate (BCM) on oral administration shows low bioavailability due to limited gastric absorption (30%) and is susceptive to substantial first pass metabolism in the liver. Bromocriptine is classified under Biopharmaceutics Classification System (BCS) as a Class II drug (low solubility, high permeability), which rationalizes the need for an alternative route to bypass dissolution-limited absorption and first-pass metabolism. It shows a biological half-life 2 to 6 h. It is used as a dopaminergic agonist indicated for Parkinson’s disease (PD). This study aims to develop, characterize and statistically optimize a BCM entrapped ultra-flexible deformable liposome (UDL) loaded into a gel formulation to study its efficacy in transdermal penetration and thereby improve its pharmacokinetic profile. Impact of different formulation factors on crucial qualities including entrapment efficiency was analyzed using a full factorial design. Hydration of deposited thin film was done to develop BCM entrapped UDL. The Optimized formulation shown zeta potential value (–) 13.0 mV and mean vesicle size of UDL was found to be 148.5 nm. In an ex-vivo diffusion study, UDL showed a significant increase in transdermal penetration across isolated rat skin was observed as compared to an aqueous BCM solution. In the in-vivo pharmacokinetic studies in Wistar rats showed a higher and prolonged drug release from UDL loaded gel formulation as compared to oral, intravenous aqueous BCM solution and BCM impregnated DIA transdermal patch. In the in-vivo pharmacokinetic studies AUC0–t for developed formulation, oral, intravenous BCM solution and BCM in adhesive based transdermal patch was found to be 30979.83, 7705.75, 20282.58 and 14753.51 ng/ml h respectively. The results of studies suggest that the BCM entrapped UDL loaded gel might be a preferable and patient compliant alternative than oral administration of BCM for management of Parkinson’s disease.

Background

Urolithiasis is often complicated by urinary tract infections caused by uropathogens, posing a significant healthcare challenge due to high recurrence rates. This necessitates the development of alternative phytotherapeutic approaches. Ficus religiosa, a traditionally valued medicinal plant, offers potential in this regard.

Objectives

The study aimed to investigate the antimicrobial and antiurolithiatic potential of F. religiosa seed extracts, focusing on their phytoconstituents, functional groups, and biological efficacy.

Methods

Seeds of F. religiosa were extracted using Soxhlet methodology with solvents of varying polarity to obtain a broad spectrum of phytochemicals. Functional groups in the extracts were characterized using Fourier transform infrared (FTIR) spectroscopy. Antimicrobial activity was assessed against three gram-positive, gram-negative, and fungal strains via the well diffusion method. Minimum inhibitory concentration (MIC) values were determined. The antiurolithiatic activity was studied through calcium oxalate nucleation assays, with Cystone as a standard. Principal component analysis (PCA) was employed to correlate phytochemical contents with biological activity.

Results

The ethyl acetate extract exhibited superior antimicrobial efficacy, showing the lowest MIC values: Escherichia coli (27.40 ± 0.10 µg/mL), Vibrio cholerae (26.43 ± 0.07 µg/mL), and Candida albicans (22.00 ± 0.577 µg/mL). All extracts displayed significant, concentration-dependent antimicrobial activity. In nucleation studies, the ethyl acetate extract effectively inhibited calcium oxalate crystallization, outperforming Cystone, producing smaller crystals (2.30 μm vs. 2.68 μm at 500 µg/mL), compared to the control (4.07 μm). PCA analysis revealed that phenolic, flavonoid, and tannin contents synergistically contributed to antimicrobial activity.

Conclusion

The ethyl acetate extract, in particular, exhibited strong efficacy, highlighting F. religiosa seeds as promising candidates for urolithiasis prevention and urinary tract infection management. This is the first comprehensive report on F. religiosa seeds demonstrating both antimicrobial and antiurolithiatic potential.

Purpose

Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disorder frequently observed in infants, where safe and effective therapies remain a clinical challenge. Methylprednisolone aceponate (MPA), a fourth-generation corticosteroid, is widely preferred due to its favorable risk–benefit profile and pediatric approval from four months of age. This study aimed to develop and evaluate novel MPA-loaded microemulsions (MEs) as safe topical formulations for infantile AD.

Methods

Oil-in-water (O/W) MEs containing 0.1% MPA were prepared using different oils and surfactant/cosurfactant (Smix) ratios. Pseudo-ternary phase diagrams were constructed to identify appropriate component ranges. The optimized ME was characterized by FTIR spectroscopy, viscosity, droplet size (DS), polydispersity index (PDI), and zeta potential (ZP). In vitro drug release was performed, and cytotoxicity was assessed by MTT assay using L929 fibroblast cells.

Results

The optimized ME formulations exhibited nano-sized droplets with low PDI, negative ZP, and suitable viscosity, indicating high stability. MPA release was 3.69 times higher in formulation A3 and 4.12 times higher in formulation A4 compared to the MPA suspension. In cell culture studies, approximately 90% cell viability was maintained after 24 h of incubation, and MTT assays confirmed that the formulations provided high biocompatibility without inducing cytotoxicity in fibroblast cells.

Conclusion

The formulated MPA-loaded ME is a secure, stable, and novel topical delivery method with significant promise for addressing infantile AD. This is, to our knowledge, the first report of an MPA-ME particularly formulated for newborns, substantiated by physicochemical characterisation and in vitro biocompatibility assessments.

Purpose

This research aims to develop a pulmonary delivery system of axitinib (AXT) as a spray-dried microparticle to address its poor solubility, variable oral bioavailability, and systemic adverse effects, thereby enhancing its potential application in LC therapy.

Methods

The microparticles were produced via spray drying using lactose and L-leucine as stabilizing carriers. The spray drying was carried out at an inlet/outlet temperature of 105 °C/60 °C, and feed rate of 2 mL/min. The formulations were characterized for production yield, drug content, solid-state analysis using DSC, PXRD, FTIR, morphology by SEM, aerosolization efficiency, and in vitro cytotoxicity activity against A549 lung carcinoma cells. Further, the stability of the optimized formulation was examined under accelerated conditions at 40 °C ± 2 °C and 75% ± 5% RH.

Results

Among the prepared formulations, the D6 formulation (84.56% of lactose, and 14.71% of L-leucine) demonstrated the most desirable performance, showing a high emitted dose (98.42%) and fine particle fraction (44.33%) with an MMAD of 2.11 μm. The solid-state studies confirmed the transformation of AXT into an amorphous form, improving the solubility of AXT. SEM images revealed smooth, spherical microparticles with good dispersibility. The cytotoxicity studies indicated greater anticancer activity for D6 (IC₅₀ = 4.85 µg/mL) compared to pure AXT (IC₅₀ = 5.95 µg/mL). The stability testing confirmed that drug integrity and aerosolization properties were retained over three months.

Conclusions

The optimized AXT spray-dried microparticles exhibited promising aerodynamic and biological properties, suggesting their suitability for pulmonary delivery. This formulation strategy offers a promising alternative to systemic administration, potentially improving local drug concentration in the lungs while limiting systemic toxicity in lung cancer therapy.

Graphical Abstract

Background

Lutein, a natural carotenoid with potent antioxidant and anti-inflammatory properties, has shown protective effects in various oxidative stress-related disorders. However, its potential to mitigate doxorubicin, an anthracycline chemotherapeutic agent known to induce atherosclerotic vascular injury, remains poorly understood. This study therefore investigated the protective role of lutein against doxorubicin-induced vascular injury in male Wistar rats.

Methods

Atherosclerotic vascular injury was induced by intraperitoneal administration of doxorubicin (15 mg/kg) for three consecutive days, followed by treatment with lutein (40 mg/kg) for 25 days. After day 28, animals were euthanized and aorta removed for biochemical and histological studies. Meanwhile, blood was collected and centrifuged for lipid profile.

Results

Doxorubicin administration led to increased vascular oxidative stress, inflammation, apoptosis, hyperlipidemia, impaired vascular tone, and loss of endothelial integrity, hallmarks of atherosclerotic injury. Lutein treatment markedly ameliorated these effects by exerting antioxidant, anti-inflammatory, anti-apoptotic, and anti-atherogenic actions. Additionally, lutein enhanced cell adhesion and improved vascular tone, suggesting a role in promoting angiogenesis and endothelial recovery.

Conclusion

Lutein effectively attenuates doxorubicin-induced atherosclerotic vascular injury in male Wistar rats, likely through modulation of oxidative stress, inflammation, and endothelial repair mechanisms.

Introduction

Breast cancer continues to be one of the primary causes of cancer-related fatalities among women globally. Missing in metastasis (MIM) is a multi-functional protein that belongs to the family of I-BAR (Inverse BAR) domain proteins and is associated with the actin cytoskeleton. 

Objectives

This study investigates the impact of the human Amniotic Mesenchymal Stem Cell (hAMSC) secretome on the migration and protein expression in breast cancer cells (MDA-MB-231).

Methods

For this purpose, hAMSCs and MDA-MB-231 cells were co-cultured for 72 h in Transwell plates, allowing the cancer cells to be exposed to the stem cell secretome. Additionally, the motility of treated MDA-MB-231 cells was assessed after 48 h using the scratch assay. Protein levels were analyzed via Western blot, focusing on MIM and ten other proteins involved in metastasis regulation, including pro-metastatic proteins (EGFR, Cortactin, Rac1, RhoA, c-Src, p-Src (Y416, Y527)), and EMT-related markers (E-cadherin, Vimentin, and Slug).

Results

Our findings indicate that the hAMSC secretome led to an increased expression of MIM and E-cadherin, alongside a reduced expression of all other proteins in MDA-MB-231 cells.

Conclusion

These results suggest that the hAMSC secretome may help inhibit breast cancer metastasis through modulation of MIM and associated pro-metastatic proteins, offering preliminary insights into its potential therapeutic application.

Purpose

Tablet sticking and film surface formation upon compaction of clopidogrel bisulfate (CB) are related to the occurrence of sintering, in which particles are fused as a result of pressure in tablet compaction. Sintering might increase tablet strength, but it also prolongs tablet disintegration. Mixing CB with a disintegrant could reduce the sintering effect and enhance tablet disintegration. Yet, the mechanism by which the disintegrant could overcome sticking is still unclear. Three disintegrants were investigated: starch, partially pregelatinized maize starch (PPS), and croscarmellose sodium (CCS).

Methods

Three ratios of CB/disintegrant were prepared (90/10, 85/15, and 80/20 w/w) to produce an 800 mg tablet with a diameter of 14 mm, and each was compacted at compaction forces of 10,000 N and 15,000 N. Visual observation, tablet structure examination by SEM and XRD, tablet tensile strength, friability, and disintegration were evaluated.

Results

SEM results showed that CB underwent sintering only on its compacted surface. At 10,000 N, CB/starch and CB/CCS 80/20 did not show sticking, but all tablets failed to pass friability test. At 15,000 N, no tablet sticking was observed at any ratio of CB/CCS and friability was less than 2%.

Conclusion

CCS was superior in reducing tablet sticking compared to starch and PPS. The variability in particle sizes and shapes of CCS enables it to fill the void surrounding CB particles, in conjunction with its good tabletability, hence it could hinder particle fusion of CB. Yet, a higher compaction pressure or a combination with other excipients is still required to increase tablet tensile strength and reduce tablet friability.