Drug Development and Industrial Pharmacy最新文献

Introduction: This study aims to develop immediate release tablet formulations of lornoxicam (LRX) using hot melt extrusion (HME)-based fused deposition modeling (FDM) focusing on the adjustment of drug release by arranging infill densities and evaluating microcrystalline cellulose II (MCC II) as a disintegrating agent for HME-FDM purposes. LRX is a poorly soluble drug that exhibits pH-dependent solubility with a high thermal degradation temperature. These characteristics make it an ideal model drug for the HME-based FDM technique.

Methods: Various filament formulations were extruded using an extruder, and suitable filaments were used to produce 3D-printed tablets. Filaments and tablets were characterized. Dissolution studies were performed on tablets with different infill densities. DSC, FTIR, XRD, and SEM analyses were conducted.

Results: Although the solubility of LRX increases with pH, disintegrating agents such as MCC II had a more significant effect on the dissolution of LRX than sodium bicarbonate, which was used as the alkalinizing pore-forming agent. Dissolution studies revealed that the dissolution of LRX was enhanced by tablet erosion. Tablet erosion increased as the infill density decreased, and an immediate release profile was reached with tablets having 25% infill density. Despite the availability of conventional immediate release LRX tablets, this newly developed formulation offers the potential to be modulated for personalized therapy via the 3D printing technique.

Conclusion: This study demonstrates the feasibility of HME-based FDM printing technology for producing immediate-release LRX tablets with consistent quality, highlighting the utilization of MCC II as a disintegrating agent that enhances LRX dissolution in this process.

Objective: Genotoxicity assays include micronucleus test, comet assay, and malformed sperm head used to investigate the protective potential of quercetin (Que) and Que nanoparticles against imidacloprid (IMI)-induced genotoxicity in Swiss albino mice.

Methods: The ionic gelation procedure was used to synthesize the Que nanoparticles and characterized for their hydrodynamic diameter, zeta potential, scanning electron microscopy (SEM), transmission electron microscopy (TEM), FT-IR, and encapsulation efficiency. A total of 48 mice were taken in eight groups with six animals in each group. Groups 1, 2, 3, and 4 received 3% gum acacia, 22 mg/kg IMI, 25 mg/kg Que and 25 mg/kg Que nanoparticles high dose (QNPs (HD)), respectively. Groups 5, 6, 7, and 8 received 22 mg/kg IMI + 25 mg/kg Que (IMI + Que), 22 mg/kg IMI + 25 mg/kg Que nanoparticles (IMI + QNPs (HD)), 22 mg/kg IMI + 12.5 mg/kg Que nanoparticle medium dose (IMI + QNPs (MD)), and 22 mg/kg IMI + 6.25 mg/kg Que nanoparticles low dose (IMI + QNPs (LD)), respectively.

Results: The IMI causes genotoxicity in bone marrow cells by increasing the frequency of micronuclei and the comet tail length. Additionally, IMI is mutagenic to germ cells, as determined by a test for aberrant sperm heads. Both Que and Que nanoparticles lessen the genotoxicity that IMI induces when administered together or separately. Histopathological findings also revealed degenerative changes in bone marrow and testes in IMI administered group as compared to control.

Conclusion: Quercetin and Que nanoparticles showed marked ameliorative effect by restoring the degenerative changes produced by IMI.

Objective: Recent developments in nanotechnology have regained hope in enabling the eradication of lung cancer, while overcoming the drawbacks of the classic therapeutics. Nevertheless, there are still formidable obstacles that hinder the translation of such platforms from the bench into the clinic. Herein, we shed light on the clinical potential of these formulations and discuss their future directions.

Significance of review: The current article sheds light on the recent advancements in the recruitment of nanoformulations against lung cancer, focusing on their unique features, merits, and demerits. Moreover, inorganic nanoparticles, including gold, silver, magnetic, and carbon nanotubes are highlighted as emerging drug delivery technologies. Furthermore, the clinical status of these formulations is discussed, with particular attention on the challenges that they encounter in their clinical translation. Lastly, the future perspectives in this promising area are inspired.

Key findings: Nanoformulations have a promising potential in improving the physico-chemical properties, pharmacokinetics, delivery efficiency, and selectivity of lung cancer therapeutics. The key challenges that encounter their clinical translation include their structural intricacy, high production cost, scale-up issues, and unclear toxicity profiles. The application of biodegradable platforms improves the biosafety of lung cancer-targeted nanomedicine. Moreover, the design of novel targeting strategies that apply a lower number of components can promote their industrial scalability and deliver them to the market at affordable prices.

Conclusions: Nanomedicines have opened up new possibilities for treating lung cancer. Focusing on tackling the challenges that hinder their clinical translation will promote the future of this area of endeavor.

Introduction: 4-methyl umbelliferon (4MU) is a coumarin with anti-inflammatory, anti-thrombotic, enzyme-inhibiting, and antioxidant properties. Despite the benefits of the compound, it is eliminated very quickly from the blood circulation through the liver, kidney, and digestive system due to its hydrophobic properties. In this study we proposed to improve the durability of 4MU by binding of 4MU to poly vinyl alcohol (PVA) and graphene oxide (GO).

Methods: The PVA-4MU-GO complex was synthesized and characterized. Release of 4MU from the complex was investigated. H9C2 cells viability was investigated and the entry of complex to the cell was analyzed using flow cytometry.

Result: UV-Vis and FTIR studies confirmed the interaction of 4MU with PVA and GO. SEM measurement also revealed a particle size around 101 nm for PVA-4MU-GO complexes. The obtained results confirmed the assembly of PVA-4MU-GO. A continuous drug release for 8 d (160 h) was achieved. Cytotoxic studies on H9C2 cell showed that PVA-4MU-GO complex is dependent to the concentration of GO and also the relation of 4MU to GO. Sustained release and penetration of PVA-4MU-GO complex into the H9C2 cell were observed.

Conclusion: PVA-4MU-GO complex is recommended as an alternative for 4MU. Synthesis the complex of PVA-4MU-GO, verifying the correct binding, showing the in vitro release of the 4MU, as well as checking its toxicity and its gradual entry into the H9C2 cell, were performed in this study.

Objective: The preparation of safranal-containing invasomes for fluconazole (FLU-IN) is investigated in the current research work to augment FLU permeation, bioavailability, and solubility via nail for transungual delivery.

Methods: FLU-IN was prepared utilizing the 'thin-film hydration process', and for optimization, 'Box-Behnken design (BBD)' was employed. Entrapment efficiency (EE), Poly-dispersity index (PDI), in vitro FLU release, vesicle size and zeta potential were used to characterize FLU-INopt. Confocal microscopy (CLSM), nail permeation investigation, and Transmission electron microscopy (TEM) were also carried out for further examination.

Results: The FLU-INopt demonstrated tiny, spherical, sealed-shape vesicles with a vesicle size of 140.3 nm, PDI of 0.1604, in vitro release of 84.32%, and entrapment efficiency of 74.65%. According to the CLSM investigation, the prepared formulation exhibits better FLU penetration over the nail than FLU suspension gel. Compared to the standard fluconazole marketed gel, the anti-fungal investigation showed that the FLU-IN gel has good anti-fungal potential against Trichophyton rubrum, Nakaseomyces glabrata and Candida albicans. Additional research on Wistar albino rats' skin irritancy supports the new FLU-IN formulation's safety for topical treatment.

Conclusion: The present study supported the claim that the developed invasomal formulation is a desirable vesicular carrier for FLU transungual delivery for the management of onychomycosis.

Objectives: Sepsis-associated acute kidney injury (SA-AKI) is a significant clinical challenge with high morbidity and mortality. Low bioavailability of protopanaxadiol (PPD) limits its clinical application. In this study, PPD was encapsulated with chitooligosaccharide (COS) modified polylactic-co-glycolic acid (PLGA) to develop novel nanomedicines for the treatment of SA-AKI.

Methods: COS-PLGA-PPD nanoparticles were prepared by emulsified solvent evaporation method, and their properties were evaluated. In vitro, the anti-inflammatory and protective effects of COS-PLGA-PPD NPs were investigated in a cellular model of LPS-induced NRK-52E cells and their uptake in Caco-2 cells. Indicators of renal injury, inflammation, and NF-κB signaling pathway were evaluated by injecting LPS into SD rats and inducing SA-AKI model in vivo. The oral bioavailability of nanoparticles was evaluated by pharmacokinetics.

Results: Compared with PPD and unmodified nanoparticles, COS-PLGA-PPD NPs were more stable, with a particle size of 139.69 nm, which enhanced the viability of NRK-52E cells, increased the uptake of Caco-2 cells, alleviated the symptoms of SA-AKI in rats, inhibited the NF-κB signaling pathway, reduced the expression of inflammatory factors, and had a bioavailability 1.7-fold that of PPD.

Conclusion: COS-PLGA-PPD NPs ameliorate LPS-induced SA-AKI in rats by inhibiting the NF-κB signaling pathway, providing a basis for the treatment of SA-AKI.

Objective: Poly(lactic-co-glycolic acid) microsphere containing leuprolide acetate - an extended-release drug delivery system whose characteristics (i.e. loading capacity, particle size and initial burst phase) depend on processing parameters.

Methods: Microspheres were prepared by water/oil/water double-emulsion solvent evaporation method; drug content in microspheres was determined by high-performance liquid chromatography (HPLC); peptide concentration in the release medium was measured by fluorescence spectrometer; particle size and particle size distribution were measured by laser diffraction method; interaction between poly(lactic-co-glycolic acid) (PLGA) and leuprolide acetate (LA) was determined by differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR).

Results: DSC curves and assay results proved LA adsorption ability of PLGA film. FTIR spectra proved ionic interactions between positive charged LA molecules and negative charged PLGA chains in phosphate buffer pH 7.4. Ten processing parameters including LA concentration (mg/mL), PLGA concentration (mg/mL), W1/O ratio (v/v), the first homogenization time (min), the first homogenization speed (rpm), O/W2 ratio (v/v), PVA concentration of W2 phase (mg/ml), the second homogenization time (s), the volume of diluted solution (ml) and nitrogen aeration time (min) have impacts on loading capacity, particle size and initial burst phase of microspheres. The release exponent (n) of Korsmeyer-Peppas model was 0.3571 (lower than 0.43), indicating that Fickian diffusion manipulated release kinetics of initial burst phase.

Conclusions: Processing parameter modification contributes to small microspheres with high loading capacity and controlled initial burst phase.

Objective: The objective of this study is to create predictive models utilizing machine learning algorithms, including Artificial Neural Networks (ANN), k-nearest neighbor (kNN), support vector machines (SVM), and linear regression, to predict critical quality attributes (CQAs) such as hardness, friability, and disintegration time of fast disintegrating tablets (FDTs).

Methods: A dataset of 864 batches of FDTs was generated by varying binder types and amounts, disintegrants, diluents, punch sizes, and compression forces. Preprocessing steps included normalizing numerical features based on industry standards, one-hot encoding for categorical variables, and addressing outliers to ensure data consistency. Four machine learning models were trained and evaluated on R² values and mean squared error (MSE). Feature importance was analyzed using permutation importance, and statistical validation (p < 0.05) and confidence intervals were computed for model performance. The 'differential_evolution' function was used to optimize the formulation.

Results: Among the models, ANN demonstrated the highest predictive accuracy, achieving R² values up to 0.9550 with the lowest MSE across training and test datasets, outperforming kNN, SVM, and linear regression. The ANN's ability to model complex, non-linear interactions between formulation variables was statistically significant, as validated through six checkpoint batches of acetylsalicylic acid FDTs. The feature importance analysis revealed compression force, binder type, and punch size as the most influential factors affecting hardness, while disintegrant type influenced friability. The 'differential_evolution' function effectively optimized the CQAs, resulting in FDTs with ideal characteristics.

Conclusion: The ANN model, integrated with differential evolution, provided a robust tool for optimizing FDT formulations by accurately predicting CQAs and reducing the need for extensive experimental trials. Compared to traditional optimization methods, ANN excels in capturing intricate multi-variable relationships, making it a valuable approach for scaling beyond acetylsalicylic acid to other formulations. This method enhances the consistency and efficiency of tablet formulation, supporting broader pharmaceutical applications.

Background: Liver in the body plays vital role including digestion, detoxification, metabolism and even production of hormones. Hepatocellular carcinoma is recognized as one of leading cause of death worldwide. Infection with hepatitis B and C virus, nonalcoholic fatty liver disease and excessive consumption of alcohol are among the most common risk factors associated with the development of hepatocellular carcinoma.

Objective: The present research study involves formulation of liposomal delivery of methanolic extract of Annona muricata as an alternative for the treatment of hepatocellular carcinoma.

Methods: The methanolic extract of Annona muricata was subjected for both nonvolatile and volatile content analysis by performing phytochemical screening and GCMS. The methanolic extract was entrapped within the liposomes for its effective delivery. The prepared liposomes were characterized in-vitro, and the optimized formulation was further evaluated against hepatocellular carcinoma induced in the animal model.

Results: The methanolic extract showed the presence of alkaloid, carbohydrate, flavonoid, tannin, proteins and acetogenins, whereas the GMCS analysis depicts presence of 12 different compounds. The optimized in-vitro analysis of prepared liposomes showed a particle size of 107.2 ± 1.7 nm, zeta potential of -30.6 mV and entrapment efficiency of 62.15%. TEM micrograph of the optimized liposome formulation has showed spherical geometry with homogenous distribution and negligible agglomeration. In-vivo anticancer study reveals the potent efficacy of the formulation for the treatment of hepatocellular carcinoma.

Conclusion: The research findings have established the efficacy of the methanolic extract of Annona muricata in the treatment of hepatocellular carcinoma.

Objective: Wound in diabetes is difficult to heal since it possesses excessive inflammation. The aim of the study was to evaluate wound healing activity of chitosan-based hydrogel containing pyroligneous acid in diabetic animals.

Significance: Pyroligneous acid, a byproduct of biochar production from palm kernel shell biomass, contained oxygenated compounds which, with extracting enrichment, could promote wound healing.

Methods: Streptozotocin-induced diabetic male jcl: ICR mice were subjected to create wounds and treat with hydrogel containing pyroligneous extract at dose strengths of 0 (placebo), 100 and 150 µg/g-gel. Commercial gel (Intrasite^®) was used as an active comparator. On 3-, 7-, 10- and 14-day post-wounding, wound contraction was rated and wound site tissues were collected. The specimens were H&E stained and microscopically examined to evaluate histological responses. The underline wound healing related cytokine and polypeptide expressions were determined using real-time PCR and western blot.

Results: It was found that the extract accelerated the healing process in a dose-dependent manner where at dose strength of 150 µg/g-gel was as effective as active comparator. It increased gene expression of the cytokine and related proteins in TGF-β/SMAD signaling pathway and may further activate diabetic induced TGF-β downregulation to restore up to the level that healthy skin tissues express. It also enhanced the expressions of Akt, FAK, RhoA and Rac-1 and evidently activated phosphorylation of Akt and FAK.

Conclusion: The study demonstrated the extract could be a novel biomaterial for healing of such a chronic inflammatory wound as the wound in diabetes.