Journal of Pharmaceutical Innovation最新文献

Background

Hibiscus rosa-sinensis L, a widely used medicinal plant, has been traditionally recognized for its therapeutic properties, prompting investigations into its phytochemical composition and bioactivity.

Purpose

This study investigates the extraction and characterization of phytochemicals from H. rosa-sinensis L., focusing on their potential antioxidant, antimitotic, and antiproliferative activities.

Methods

The extraction was conducted using various solvents by maceration method. Then different dilutions of extracts were used to carry out phytochemical analysis and bioactivities assessment.

Results

The yield analysis revealed that n-butanol produced the highest extraction yield (6.05%), while chloroform yielded the lowest (3.6%). Qualitative and quantitative assessments confirmed the presence of flavonoids, tannins, and phytosterols, with High-Performance Liquid Chromatography (HPLC) revealing Myricetin and Quercetin as the predominant flavonoids in the acetone extract, highlighting their potential health benefits due to their antioxidant properties. Furthermore, the antioxidant activity was highest in the acetone extract (71.13 ± 0.03%) at a concentration of 2 mg/ml. The antimitotic activity was assessed using Allium cepa root tips, where the methanolic extract showed the strongest action, reducing the mitotic index significantly to 10% at 0.25 mg/ml. The presence of chromosomal abnormalities, such as micronuclei and fragmented nuclei, confirmed the cytotoxic effects of the extracts. Additionally, the chloroform extract exhibited the lowest cell viability (25 ± 0.557%) in antiproliferative assays against yeast models, suggesting a significant cytotoxic potential.

Conclusion

The study concludes that H. rosa-sinensis possesses considerable antioxidant, antimitotic, and antiproliferative properties, warranting further exploration of its phytochemical constituents for potential therapeutic applications in drug discovery.

Background

Carica papaya L. leaf extract has long been recognized for its therapeutic potential in dengue-associated thrombocytopenia through enhancement of platelet production and inhibition of dengue viral proteases. However, its oral delivery is hindered by poor bioavailability, instability of phytochemicals, and lack of optimized delivery platforms.

Novelty and Objective

This study reports, for the first time, the development and optimization of an oral pro-transferosome tablet of Carica papaya leaf extract, enabling improved bioavailability, storage stability, and therapeutic efficacy. Furthermore, it elucidates a new mechanistic hypothesis the complementary and differential molecular targeting of ALOX-12 by carpaine and PTAFR by quercetin providing deeper insight into its platelet-enhancing and anti-dengue actions.

Methods

Using a Box-Behnken Design, three critical formulation variables phospholipid concentration, edge activator content, and extract-to-lipid ratio were optimized for entrapment efficiency, particle size, and zeta potential. The resulting tablets underwent physicochemical characterization, vesicle morphology assessment, tablet quality evaluation, in vitro drug release, and accelerated stability testing. Molecular docking was performed to determine binding affinities of carpaine and quercetin to platelet-production-related proteins (ALOX-12, PTAFR) and dengue viral proteases.

Results

The optimized oral pro-transferosome tablets achieved 87.4% entrapment efficiency, 145.7 nm particle size, and − 32.5 mV zeta potential, indicating a stable vesicular system. Morphology confirmed nanosized spherical vesicles with narrow distribution. Tablet evaluation showed consistent weight uniformity, optimal hardness, low friability, and rapid disintegration (~ 4.2 min). In vitro release revealed sustained carpaine release (88% over 12 h), supporting prolonged therapeutic effect. Docking revealed strong binding of carpaine to ALOX-12, while quercetin showed high affinity to PTAFR and negligible interaction with ALOX-12, suggesting dual but distinct platelet-regulating pathways.

Conclusion

This is the first report of an oral pro-transferosome tablet formulation of Carica papaya leaf extract, combined with the discovery of distinct molecular targets for its key bioactives. These findings not only establish a novel, clinically relevant delivery system but also propose a new mechanistic basis for its efficacy against dengue-induced thrombocytopenia.

Graphical Abstract

This study addresses the rising incidence of breast cancer by developing advanced therapeutic and analytical solutions. The anticancer potential of biochanin A and quercetin was assessed through in silico molecular docking against hormone-positive breast cancer receptors, with docking scores ranging from − 5.63 to − 6.85 kcal/mol, indicating binding affinities towards hormone positive breast cancer receptors. An analytical quality-by-design (AQbD) approach guided the development of a novel reversed-phase high-performance liquid chromatography (RP-HPLC) method for the simultaneous identification and quantification of both compounds. Key method parameters were identified using an Ishikawa fishbone diagram and optimized using a four-factor two-level fractional factorial design. The optimal chromatographic conditions employed a C18 column with a mobile phase of 0.1% formic acid and acetonitrile (40:60, v/v), pH 2.5, at 34 °C and a flow rate of 1 mL/min. The method demonstrated excellent specificity, linearity, precision, and accuracy in accordance with the ICH Q2 (R1) guidelines. Fruther, comprehensive greenness assessments using the Analytical Eco-Scale, Green Analytical Procedure Index, and Analytical GREEnness Metric (score: 0.72) confirmed the eco-friendly profile. The validated method was applied to dual drug-loaded nanofibers to successfully determine the entrapment efficiency, in vitro release, and release kinetics. The nanofibers exhibited sustained drug release over 48 h and followed a non-Fickian diffusion mechanism. This comprehensive approach not only provides a robust analytical solution for the simultaneous analysis of advanced matrices but also extends its applicability to other pharmaceutical formulations. It distinguishes itself from existing literature through the integration of green chemistry, systematic optimization, and direct relevance to drug delivery system.

Purpose

This study reports the first statistically optimized dual-surfactant wintergreen oil nanoemulsion, developed using a Box–Behnken design (BBD), that demonstrates enhanced antioxidant activity, stability, and topical permeation of methyl salicylate for dermal therapy. The research aimed to formulate and characterize a stable nanoemulsion system to improve the topical delivery efficiency and antioxidant performance of methyl salicylate.

Methods

The nanoemulsion was prepared using a high-speed homogenization–ultrasonication method, employing Tween 80 and sodium dodecyl sulfate (SDS) as surfactants. Critical formulation parameters affecting particle sizeand zeta potential were optimized using BBD. Comprehensive characterization included droplet size, polydispersity index (PDI), zeta potential, pH, viscosity, and stability under accelerated conditions. Antioxidant potential was evaluated through DPPH radical scavenging, permanganate assay, and superoxide dismutase (SOD) enzymatic assays, complemented by cellular ROS inhibition imaging. Ex vivo permeation was conducted using goat skin in a Franz diffusion system to validate improved diffusion behavior (Modi et al.in Braz J Pharm Sci. 2023;59:e01672, 2023.

Results

The optimized nanoemulsion displayed a mean droplet size of 420 nm, PDI 0.28, and zeta potential − 45 mV, evidencing strong colloidal stability. The formulation’s pH 5.5 was within the physiological skin range. In vitro release demonstrated a sustained 24-hour profile, whereas ex vivo results confirmed enhanced diffusion flux compared to the free oil. The nanoemulsion exhibited 56.7% DPPH radical scavenging and a 67.3% increase in SOD activity, indicating significant antioxidant efficacy. Fluorescence imaging further revealed decreased intracellular ROS accumulation. Stability analysis over three months confirmed minimal alterations in physicochemical parameters.

Conclusion

The developed BBD-optimized dual-surfactant wintergreen oil nanoemulsion offers an innovative, thermodynamically stable platform with improved antioxidant activity, skin permeability, and storage stability. Its synergistic surfactant system ensures enhanced topical bioavailability of methyl salicylate, highlighting its potential for antioxidant and anti-inflammatory dermatological applications. Future research should focus on in vivo efficacy and biochemical antioxidant evaluation (CAT, GPx, and MDA) for clinical translation.

Graphical Abstract

Purpose

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and the second leading cause of cancer-related deaths, representing a major global health burden. The limitations and toxicity of conventional therapies have motivated extensive research into medicinal plants as alternative or complementary anticancer agents. Silymarin is recognized as a natural compound with significant anti-inflammatory and antioxidant properties. However, its clinical application is limited by poor solubility and low oral bioavailability. To address these challenges and enhance its therapeutic potential against CRC, this study focused on developing a nanoemulsion (NE) formulation of silymarin.

Methods

First, a silymarin-loaded NE was prepared using the spontaneous emulsification method, and the formulation that successfully passed the physical stability tests was selected for further studies. This formulation was evaluated in terms of particle size, morphology, surface potential, and antioxidant activity. In addition, its antiproliferative and apoptosis-inducing effects were assessed in the human colorectal carcinoma cell line HCT-116.

Results

Silymarin exhibited the highest solubility in fish oil, and an optimized NE containing 15 mg/mL of silymarin was stable and transparent, whereas higher concentrations resulted in turbidity and instability. Thermodynamic stability tests confirmed its robustness under stress conditions. The selected NE displayed particle sizes below 20 nm, spherical morphology, and favorable zeta potential values. Antioxidant assays demonstrated that silymarin-loaded NEs had significantly enhanced radical scavenging activity compared to free silymarin or unloaded NEs. In HCT-116 cells, silymarin-loaded NEs showed the strongest cytotoxic effect, with the lowest IC50, surpassing free silymarin and other controls. Apoptosis assays further confirmed that silymarin-loaded NEs induced markedly higher apoptotic cell death compared to the free compound.

Conclusion

These results indicate that silymarin-loaded NE is a promising delivery system capable of significantly enhancing the therapeutic efficacy of silymarin against CRC.

Introduction

The objectives of evaluating the toxicological study of polysaccharide-based multiparticulate formulation should be explicitly the safety of oral drug deliver through clinical observations, biochemical tests, and histopathological analyses in animal models. The safety of oral drug delivery using biopolymer-based multi-particulate formulation was assessed by acute and sub-acute toxicity. The acute and sub-acute studies were conducted on male and female rats, following the OECD Guideline 423 & 407 for the formulation based on polysaccharides as a biomaterial.

Methods

The white albino rats were split into four groups (I-IV), and the polysaccharide-based formulation was administered in different dosages of 50 mg/kg, 100 mg/kg, and 200 mg/kg of body weight, except for the control group (I), which did not receive any treatment. The rats were observed for sub-acute toxicities, while body weight, food intake, necropsy, haematology, biochemistry and histopathology were examined in animals.

Results

In the acute toxicity study, no toxic signs were observed during the study and no abnormalities were observed after oral administration. Sub-acute toxicity studies showed no death and no abnormalities in the rats treated with the multi-particulate formulation. A repeated-measures analysis of variance (ANOVA), which uses food intake, water intake, and body weight to evaluate the changes over time, was used. The statistical significance was determined by a P-value less than or equal to 0.05.The histopathology results of the vital organs did not show any abnormalities.

Conclusion

Study results confirmed that a polysaccharide-based multi-particulate formulation was not toxic and does not pose a significant safety risk. It is possible that oral delivery of drugs could be made safe and efficient by using such formulations.

Graphical Abstract

Purpose

COVID-19 pandemic has driven the urgent need for effective antiviral treatments and strategies to combat its life-threatening complications. This study aims to develop a combination therapy approach using daclatasvir, as an antiviral agent, and xanthone, as a potent anti-inflammatory and antithrombotic compound, delivered via Bilosome-Chitosan Nanoparticles (BCNP).

Methods

The impact of varying the bilosome-to-chitosan ratio on the particle size (PS), zeta potential (ZP), and encapsulation efficiency (EE%) was evaluated. An optimized formula was prepared and tested for its antiviral activity and its potential for pulmonary protection in acute respiratory distress syndrome (ARDS) on mice model.

Results

The optimized formulation (O₁) showed a PS of 222.67 nm, a polydispersity index of 0.368, a ZP of -19.10 mV, and EE% of 83.78% for xanthone and 78.98% for daclatasvir. Controlled release profiles were attained, with daclatasvir released over 24 h and xanthone sustained for up to 72 h. The optimized formula showed promising deposition lung profile when tested using MPPD modelling. O₁ demonstrated strong antiviral activity against SARS-CoV-2, with a selectivity index (SI = 5.02) and an IC50 of 3.87 µM. Additionally, the formulation exhibited pulmonary protective effects by modulating the LncGAS5/ACE2 pathway, with significant improvements in the lungs of the mice model, offering a potential therapeutic strategy against ARDS, a severe and often fatal COVID-19 complication.

Conclusion

A successful BCNP formulation combining daclatasvir and xanthone was prepared, providing a promising combination therapy approach for COVID-19 treatment and ARDS prevention.

Lornoxicam-loaded chitosan-coated Litsea lipid nanocarriers (LRX-CS-LLCs) were developed as an innovative oral delivery system, combining the synergistic anti-inflammatory effects of Litsea cubeba oil with the mucoadhesive properties of chitosan. The GC/MS analysis of Litsea cubeba oil identified α-citral (47.56%), β-citral (26.86%), and D-limonene (14.00%). Various LRX-loaded LLCs were prepared and optimized. Fourier transform-infrared (FTIR) and differential scanning calorimetry (DSC) confirmed its structural integrity. The optimized (LRX-CS-LLCs) exhibited a particle size of 165.4 ± 6.3 nm, zeta potential of + 26.3 ± 3.2 mV, and entrapment effectiveness of 98.2%. In vitro release followed a controlled kinetic profile. In vivo, LRX-CS-LLCs significantly reduced carrageenan-induced paw edema (77 ± 1.86% inhibition) and PGE2, COX-2, and TNF-α levels by 4.4-, 3.6-, and 3-fold, respectively, compared to the positive control group. Histopathological examinations confirmed normal tissue architecture. Notably, LRX-CS-LLCs outperformed pure-LRX, marketed-LRX, and uncoated-LRX-LLCs, emphasizing its promise as an effective oral therapeutic approach for enhanced management of inflammatory conditions.

Purpose

Polycaprolactone nanoparticles (PCLNPs) are biodegradable carriers widely investigated for drug delivery applications. Their hydrophobic nature and high encapsulation efficiency make them ideal for sustained drug release. This study aimed to encapsulate licofelone (LF), a dual COX/5-LOX inhibitor, within PCLNPs to enhance its therapeutic efficacy for osteoarthritis treatment through transdermal administration.

Methods

LF loaded PCLNPs were formulated using the nanoprecipitation method. A 2³ full factorial design was employed by varying PCL (100 or 150 mg), PVA (150 or 300 mg), and SDC (10 or 20 mg) at two levels each. The optimum formula was F8, consisting of 150 mg PCL, 300 mg PVA, and 20 mg SDC.

Results

F8 formulation exhibited a spherical shape with a particle size (PS) of 269.3 ± 1.90 nm, an encapsulation efficiency (EE%) of 89 ± 0.56%, a polydispersity index (PDI) of 0.21 ± 0.02, and a zeta potential (ZP) of -27.85 ± 0.07 mV. The F8 gel exhibited a sustained-release profile, with drug permeation across excised rat skin 2.47-fold higher than that of the LF gel (n = 3, p < 0.05). In vivo evaluation revealed significant chondroprotective and regenerative effects in a monoiodoacetate (MIA)-induced osteoarthritis rat model. F8 gel suppressed the release of inflammatory and pain mediators (5-LOX, COX, LTB₄, and PGE2) and serum cartilage degradation products (CTX-II and COMP) after 10 days of treatment. Histological evaluation further confirmed its ability to prevent cartilage surface depletion and matrix loss.

Conclusion

The optimized F8 gel achieved sustained LF release for approximately 20 h, enhanced ex vivo permeation by 2.47-fold relative to LF gel, and significantly reduced inflammatory mediators and cartilage degradation markers in vivo, highlighting its potential as a promising transdermal therapy for osteoarthritis management.

Graphical Abstract