Drug Development and Industrial Pharmacy最新文献

Objective: D-Limonene (D-LMN) is a potential anti-oral cancer agent. The incorporation of D-LMN into a nanoemulsion enhances its potential efficacy against oral cancer cells by improving its aqueous compatibility. This study evaluated the impact of surfactant type and concentration on their properties through experimental and molecular dynamics studies.

Methods: D-LMN nanoemulsions were produced using different polyoxyethylene nonionic surfactants. The nanoemulsions were compared on droplet size, size distribution, zeta potential, droplet morphology, stability, interaction among molecules, anticancer activity, and cell death mechanism. Molecular dynamics simulations were also conducted to elucidate the dynamics of the components.

Results: Cremophor RH40 and Tween 60 yielded a nanoemulsion with a small droplet size (<100 nm). Cremophor RH40 also produced the nanoemulsion with the narrowest size distribution. Two-dimensional nuclear Overhauser effect spectroscopy-nuclear magnetic resonance and molecular dynamic simulation studies revealed that Cremophor RH40 effectively produced nanoemulsions with small droplets and high stability. The nanoemulsions formulated with Tween 60 exhibited more potent inhibitory effects against oral cancer cells than those with Cremophor RH40. However, surfactant type did not influence the mechanism underlying the apoptotic.

Conclusions: This study demonstrated that surfactants with an intermediate hydrophilic-lipophilic balance of approximately 15, particularly those with large polar heads and multiple hydrocarbon chains, were suitable for the production of anti-oral cancer D-LMN nanoemulsions by phase-inversion temperature technique.

Objective: To explore the mechanisms, applications, and future potential of microneedle-based wearable sensors for continuous, minimally invasive monitoring of biomarkers in interstitial fluid (ISF), highlighting their role in revolutionizing healthcare diagnostics and personalized medicine.

Significance: Microneedle-based sensors offer a groundbreaking alternative to conventional invasive techniques by enabling real-time monitoring of critical biomarkers such as glucose, lactate, electrolytes, pH, and oxygen. Their ability to access ISF-biochemically similar to blood-allows for accurate physiological assessment without the need for blood draws, thereby improving patient compliance and enabling broader clinical and non-clinical applications.This review synthesizes findings from recent studies on the design, sensing mechanisms (enzymatic, electrochemical, and potentiometric), and fabrication technologies of microneedle-based sensors. It evaluates current research trends, clinical trials, and advances in materials science aimed at overcoming existing limitations in sensor stability, manufacturing scalability, and cost.

Results: Microneedle-based sensors have demonstrated promising results in applications including diabetes management, athletic performance monitoring, and assessment of metabolic and hydration status. Innovations in biocompatible materials and sensor integration have improved precision and functionality. However, issues related to sensor longevity, calibration accuracy, and environmental robustness remain under active investigation.

Conclusions: Microneedle-based wearable sensors represent a transformative approach in continuous health monitoring, offering significant benefits in noninvasive diagnostics and personalized medicine. Ongoing research and development efforts are expected to address current challenges, paving the way for wider clinical adoption and integration into routine healthcare practice.

Objective: The goal of this research was to create inhalable microparticles to ensure the continuous delivery of sildenafil citrate (SC) to treat pulmonary arterial hypertension (PAH). This was done to address the limitations of SC, including its short half-life and systemic side effects.

Methods: To create the inhalable microparticles, a particle engineering method called the quasi-emulsion solvent diffusion method was utilized. The study employed quality by design (QbD), a regulatory-based approach, to enhance the final product's quality. The optimization of microparticles was achieved using central composite design to enhance micromeritics properties and sustain drug release profiles. Characterization studies, including FTIR, differential scanning calorimetry (DSC), scanning electron microscopy, XRD, and surface morphology analysis, were conducted to evaluate the microparticles. Aerodynamic properties were measured to predict where particles will be deposited in the respiratory tract.

Results: The optimized formulated microparticles had an acceptable mean particle size and an entrapment efficiency greater than 90%. The optimized microparticles demonstrated a sustained drug release of 80.42 ± 0.23% over 24 h. Aerodynamic properties showed a mass median aerodynamic diameter of 3.45 ± 0.0 µm, a fine particle fraction of 21%, and 77.29 ± 2.9% of the dose recovered from the inhaler. Modified tapped density measurements indicated improved flow properties of the microparticles.

Conclusion: The QbD approach was successfully employed to formulate inhalable microparticles for sustained pulmonary delivery. The optimized microparticles exhibited enhanced micromeritics properties and sustained drug release profiles, making them a promising option for the treatment of PAH.

Objective: To establish a comprehensive pharmacognostic, physicochemical, phytochemical characteristics analysis and toxicity potential of Ehretia microphylla leaves.

Significance: The phytochemical profile of medicinal plants varies with environmental and climatic factors making the preliminary analysis essential. This study is the first to report the GC-MS profile and toxicity using brine shrimp lethality assay of E. microphylla leaves contributing new data on its phytochemical profile and toxicity profile supporting its safety and potential for herbal drug development.

Methods: Organoleptic and fluorescence analyses were conducted to determine sensory and chemical properties. Physicochemical parameters such as ash values, extractable values and moisture content were measured. Phytochemical profiling was carried out using Gas Chromatography-Mass Spectrometry. Toxicity was evaluated using brine shrimp lethality assay and the IC₅₀ was determined.

Results: The sample exhibited army green color, characteristic odor, bitter taste and coarse texture in organoleptic analysis. Fluorescence analysis showed the sample with changes from green to pink on UV and visible light. The physicochemical evaluation also established the standard values of ash content, extractive values and moisture content. GC-MS revealed 32 bioactive compounds. The brine shrimp lethality assay indicated moderate toxic activity with an IC₅₀ of 472.24 µg/mL according Meyer's cytotoxicity index.

Conclusion: This study presents a detailed scientific profile of E. microphylla leaves, which gives evidence for their potency as potential therapeutic agents. The findings validate the traditional medicinal applications and provide a basis for drug development studies in the future.

Purposes: The limitations of current sunscreens in protecting against skin cancer and aging have been acknowledged. The use of Rheum ribes extract, rich in phenolic compounds and with strong antioxidant activity, for sunscreen applications has not been extensively studied. This study aims to develop a sunscreen gel containing Rheum ribes (Rhubarb) root extract-loaded solid lipid nanoparticles (SLNs) and evaluate its sun protection factor (SPF) through in vitro testing.

Methods: Rheum ribes extract-loaded SLNs were manufactured by an emulsification-solvent evaporation method. The impact of glyceryl monostearate (GMS) concentration on SLN size, polydispersity index (PDI), entrapment efficiency (EE), and in vitro drug release was investigated. The optimized formulation was incorporated into a gel base, and its SPF was determined using spectrophotometric techniques. Skin permeation and retention studies, as well as skin irritation and cytotoxicity assessments, were conducted.

Results: The optimized extract-loaded SLN formulation exhibited a nano-sized diameter (298.07 ± 14.54 nm), uniform distribution (PDI = 0.308 ± 0.001), high entrapment efficiency (69.18 ± 2.60%), and significant skin permeation (32.03 ± 1.44% after 24 h) and retention (6.42 ± 0.39 mg/cm² after 24 h). This formulation demonstrated a substantially higher SPF (17.435) than the simple extract gel (SPF = 1.913). All gel preparations were found to be nonirritating and non-cytotoxic.

Conclusion: This study demonstrates the potential of Rheum ribes extract-loaded SLNs for developing effective and safe sunscreen gels. The optimized nanogel formulation achieved significant SPF enhancement while maintaining skin compatibility, highlighting its promising application in cosmetic sun protection.

Objective: Biocompatible drug delivery systems that endure stomach acidity while enabling controlled release in the colon are essential for enhancing bioavailability.

Significance: This study presents Terminalia arjuna (T. arjuna) gum, a plant-based substitute for synthetic excipients and a natural, biodegradable polymer for controlled drug delivery. It helps create safer, more efficient oral formulations with more stability of acid-labile drugs.

Method: T. arjuna gum was utilized to create plain, blended (T. arjuna gum and sodium alginate were used in a blended formulation to increase stability, drug entrapment, and controlled release), and coated (Propylene glycol and gum mixture was used as the coating material) microbeads via the ionic gelation method.

Result: Characterization showed that the size of plain microbeads was 645.67 ± 7.74 μm, while the size of coated microbeads was 586.23 ± 7.18 μm. Drug entrapment efficiency ranged from 67.06% to 88.12%. Swelling studies in pH 7.4 buffer revealed that coated microbeads had a higher swelling index (1.47 ± 0.09) than blended microbeads (1.18 ± 0.06). In vitro release studies demonstrated sustained release, as predicted by the Korsmeyer-Peppas model, indicating non-Fickian diffusion. Scanning Electron Microscopy (SEM) results revealed spherical microbeads with varying surface morphologies, including rough, porous, and smooth textures, depending on the formulation. Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC) confirm the stability of microbeads. Powder X-ray Diffraction (PXRD) confirmed the amorphous form of P-Na within the microbeads, and Fourier-Transform Infrared Spectroscopy (FTIR) validated successful drug entrapment without significant interactions with the polymer. Acute toxicity studies on Swiss albino mice showed no adverse effects, and in vivo pharmacokinetic studies in rabbits demonstrated a prolonged P-Na half-life, increasing from 1.12 to 2.24 hrs with a C_max of 2264.8 ng/mL.

Conclusion: These findings suggest that T. arjuna gum-based microbeads are promising candidates for sustained drug delivery applications. Future research should focus on optimizing these formulations for various drugs, exploring additional therapeutic applications, and investigating the long-term stability of T. arjuna gum-based systems for potential clinical use.

Objective: To investigate the influence of varied actuation forces on the quality assessment of pressurized metered-dose inhalers(pMDIs).

Methods: Both manual and automatic methods were employed to assess the effects of manual actuation and automatic actuation (with different set actuation forces) on the delivered dose uniformity (DDU), emitted dose per actuation (EDPA), and aerodynamic particle size distribution (APSD) results of pMDIs.

Results: When manual actuation was performed, the discrepancies in the DDU were observed, whereas differences in the EDPA and APSD results were not evident. When utilizing automatic actuation, the results for DDU, EDPA, and APSD all exhibited good uniformity. However, it was observed that inadequate actuation force, insufficient to fully open the valve, resulted in lower outcomes for all the aforementioned parameters. And when the actuation speed is excessively low, it results in a decline in the FPF value.

Conclusions: The process of routine manual testing for DDU in inhalation aerosols, as well as methodology transfer in this field, necessitates meticulous attention to the standardization of operation techniques and actuation forces among diverse experimenters. Furthermore, using automated actuation can avoid variations due to manual operation and achieve good uniformity of results. However, when employing automatic actuation, it is crucial to select an actuation force that effectively ensures complete valve opening, thereby safeguarding the accuracy and reliability of the inhalation aerosol product. This suggests that attention should be paid to patients with limited hand strength (such as children and the elderly) when using aerosols.

Objective: This article reviewed the recent research findings of diabetic wound healing including molecular targets, signaling pathways, and nanotherapeutics for diabetic wound healing.

Significance: The prevalence of diabetes (DI) is rising daily throughout the world, and one of the main issues for diabetic patients is poor wound healing. Therefore, new molecular target identification and advanced drug delivery systems development are necessary for the effective treatment of diabetic wounds.

Method: In this review, we briefly discussed the different molecular targets for selective drug delivery to the diabetic wound. This review also elaborated on the recent nanotechnology-based drug delivery systems for the healing of diabetic wounds.

Results: The diabetic wound healing (DIWH) process follows the partial or uncoordinated route and delays the acute and chronic wound healing. Therefore, various molecular targets have been explored for the treatment of DIWH such as growth factors, cytokines, neuropeptides, immunomodulators, chemokines, and epigenetic regulators. Several signaling pathways were also investigated as a molecular target for diabetic wound healing like STAT3 pathway, HIF-1 signaling, AMPK signaling, Akt/mTOR pathway, and Notch signaling. Advanced drug delivery systems such as nanofibers, nanoparticulate systems, nanogels, and gene therapy showed promising results in diabetic wound healing.

Conclusion: This review summarized the pathogenesis, challenges, molecular targets, conventional therapy, and nanotherapeutics for DIWH. Development in the area of new molecular targets and molecular targeting approaches using nanotechnology offer a promising treatment option for diabetic wounds. Further clinical studies are still needed to prove the potential of nanotherapeutics for diabetic wound healing.

Objective: The aerosol delivery of the novel anti-tubercular drug delamanid for pulmonary targeting holds promise for the effective treatment of multi-drug-resistant tuberculosis. Here, we developed a microemulsion formulation of delamanid for nebulization, evaluating its potential bioactivity.

Methods: Herein, we attempted to develop microemulsion formulations loaded delamanid for nebulization and their physicochemical characteristics were assessed. The formulation was checked for aerosol characteristics, cytotoxic potential, in vitro antimycobacterial activity, and autophagy.

Results: The optimized formulations, nebulized into a next-generation impactor, exhibited a fine particle fraction of 63.12%, ensuring efficient in vitro deposition. In vitro evaluations revealed that formulation did not demonstrate any cytotoxic potential on respiratory cell lines up to 2.5 µg/mL and lack of inflammatory cytokines production and nitric oxide from macrophage NR8383 cells, signified its safety. The flow cytometry analysis revealed that the elimination of Mycobacterium bovis by formulation after day 4, with considerably low minimum bactericidal concentration. The formulation demonstrated adequate macrophage autophagic activity when evaluated using confocal laser scanning microscopy and Western blot.

Conclusion: Consequently, the aerosolized microemulsion of delamanid for pulmonary delivery may serve as an effective therapy for MDR-TB, necessitating further in vivo studies.

Background: In this study, we aimed to prepare, evaluate, and compare drug-loaded pellets of ketoprofen coated with different triggering mechanisms for colonic delivery.

Objective: The purpose of this study was to compare Eudragit S100 and Eudragit L100 based pH-dependent, hydroxypropyl cellulose and ethyl cellulose-based time-dependent and high methoxylated pectin and ethyl cellulose-based colonic bacterial enzymatic degradation-dependent coatings over drug-loaded pellets for most efficient colon targeting.

Methods: Any possible drug-polymer interactions were analyzed using Fourier-transform infrared spectroscopy and differential scanning calorimetry. Drug-loaded pellets were prepared using powder layering technology. Different batches of coated pellets were prepared for in vitro evaluation, and optimized batches were selected. These optimized batches were investigated for surface topography by scanning electron microscopy and for colon targeting efficiency by in vivo X-ray roentgenography and gamma scintigraphy studies in white New Zealand rabbits.

Results: The drug and polymers were found to be compatible. The prepared coated multi-particulates exhibited favorable micrometric properties. In vitro dissolution studies showed that the polysaccharide pectin high methoxylated and ethyl cellulose-coated optimized batch limited drug release to 16.724 ± 1.124% in the upper gastrointestinal tract and released up to 91.556 ± 3.144% in the colon following zero-order Korsmeyer-peppas super case-II transport (mean dissolution time 36.1779 h). Scanning electron microscopy analysis confirmed the surface characteristics of the pellets before and after dissolution. In vivo studies in New Zealand white rabbits using X-ray roentgenography and gamma scintigraphy demonstrated the optimized batch's gastrointestinal transit and colon targeting efficiency.

Conclusion: Statistically, the polysaccharide-based formulation showed promising results for targeted drug release in the colon.