Drug Development and Industrial Pharmacy最新文献

Objectives: This study aimed to develop and evaluate rifampicin (RIF) and isoniazid (INH) co-loaded liposome for sustained drug delivery to enhance therapeutic efficacy against tuberculosis (TB) and overcome challenges associated with prolonged treatment and drug resistance.

Significance: The novel biocompatible liposomal system enables sustained co-delivery of RIF and INH, providing a scalable and stable platform with enhanced antimicrobial efficacy and strong potential to advance tuberculosis therapy.

Methods: Liposome were prepared using soybean lecithin and cholesterol (L-CH) via rotary evaporator-assisted thin film hydration, optimized by Box-Behnken design, and characterized for size, PDI, entrapment efficiency, and physicochemical properties (FT-IR, DSC, HR-TEM). In vitro release, accelerated stability, antimicrobial efficacy against M. smegmatis and M. tuberculosis H₃₇Rv, and LC-MS/MS-based metabolomic profiling were systematically evaluated.

Results: The optimized liposome exhibited a mean size of 129.5 ± 2.20 nm, PDI of 0.369 ± 0.06, and entrapment efficiencies of 63.84 ± 1.62% (RIF) and 56.92 ± 1.69% (INH). The release study indicated sustained diffusion-controlled kinetics consistent with the Higuchi model, achieving cumulative releases of approximately 92% for INH and 85% for RIF over a 45-hour period. The accelerated stability studies confirmed negligible drug degradation, while antimicrobial assays demonstrated a twofold reduction in MIC relative to free drugs, and metabolomic profiling indicated modulation of glutathione, citric acid, and tyrosine pathways associated with enhanced redox balance and antimicrobial activity.

Conclusions: The co-loaded RIF-INH liposomal system offers a promising, clinically translatable approach for sustained drug release and improved tuberculosis therapy.

Objective: To develop a green and efficient ultrasound-assisted extraction (UAE) process to obtain bioactive resins from Cannabis sativa with potential pharmaceutical applications, optimizing extraction parameters to maximize antioxidant capacity and total polyphenol content.

Significance: UAE using ethanol under mild temperature and time conditions as a green technique was applied to reduce solvent consumption, energy demand, and extraction time while preserving thermolabile bioactive compounds. Optimizing UAE enables the recovery of cannabinoid- and terpene-rich extracts that may serve as natural active pharmaceutical ingredients or functional excipients for drug development. This study integrates a Doehlert-based optimization of UAE with a functional evaluation of antioxidant efficiency and antimicrobial activity, providing a comprehensive framework for the development of cannabis-derived pharmaceutical ingredients.

Methods: A Doehlert experimental design combined with response surface methodology was employed to optimize temperature and extraction time. The optimized extract was characterized for its phytochemical composition. Antimicrobial activity was evaluated against Gram-positive and Gram-negative bacterial strains to assess potential therapeutic relevance.

Results: Under optimal conditions (54.5 °C, 28 min 25 s), the extract showed a total phenolic content of approximately 0.11 mg gallic acid/mg resin and an IC₅₀ value of about 0.24 mg resin/mL extract, indicating enhanced antioxidant performance compared to non-optimized conditions. Also, it showed selective bactericidal activity against Staphylococcus aureus ATCC 25923 and Staphylococcus epidermidis ATCC 12228, while Gram-negative strains remained resistant.

Conclusion: UAE extraction efficiently recovered antioxidant and selectively antimicrobial compounds from Cannabis sativa resins under mild, eco-friendly conditions, supporting their potential use as bioactive ingredients in pharmaceuticals.

Objective: The aim of this study was to develop a chemotherapy drug paclitaxel (PTX) and a tumor-specific ROS generation agent β-lapachone(LAP) co-loaded human serum albumin (HSA)-based nanoparticles (ANPs) for synergistic anticancer therapy.

Significance: Albumin-based nanoparticles (ANPs) offer unique advantages for antitumor drug delivery system, including non-immunogenicity and inherent tumor-targeting capacity. In this study, we mimicked the natural fatty acid binding process in vivo to construct ANPs to synergistically elevate ROS with β-lapachone for cooperative cancer therapy.

Methods: First, a polyethylene glycol monostearate(PGM) modified redox-sensitive paclitaxel prodrug(PTX-SS-PGM) was synthesized and stearic acid capable of binding with HSA was introduced. Further, a LAP/PTX-SS-PGM complex was engineered through the π - π stacking interaction and H-bonding between LAP and PTX. The PTX and LAP co-loaded ANPs (PTX-SS-PGM&LAP@HSA) were obtained through the binding between LAP/PTX-SS-PGM complex and HSA.

Results: The percentage of apoptosis for PTX, Abraxane^®, PTX-SS-PGM@HSA ANPs, and PTX-SS-PGM&LAP@HSA ANPs was 8.17%, 9.53%, 15.17%, and 28.6%, respectively, demonstrating synergistic cytotoxicity effect. The in vivo imaging test confirmed that PTX-SS-PGM&LAP@HSA had targeting ability to tumor tissues. The obtained ANPs exhibited better tumor growth inhibition in vitro and in vivo.

Introduction: In the early stages of drug development, evaluating physicochemical properties is crucial for anticipating a compound's absorption, distribution, and therapeutic efficacy. The distribution coefficient (logD), which accounts for both ionized and unionized species at physiological pH, provides a more biorelevant parameter than the traditional partition coefficient (logP).

Objective: The aim of the paper was to determine the distribution coefficient of gliclazide (weak acid, BCS class II) and metformin (weak base, BCS class III) under different experimental conditions.

Methods: The n-octanol-water system was used as a model for in vivo gastrointestinal absorption, and cyclohexane-water for in vivo blood-brain barrier permeation. The influence of deoxycholic acid as a potential permeability enhancer was also examined. The data were compared with in vivo results in healthy and diabetic rats.

Results: Metformin showed logD values from -1.70 to -1.20 (without DCA) and from -1.64 to -1.16 (with DCA) in the n-octanol/water system, while in cyclohexane/water, values ranged from -2.06 to -1.18 (without DCA) and from -1.61 to -1.20 (with DCA). Gliclazide exhibited logD values of 0.25-2.02 (without DCA) and 0.24-2.17 (with DCA) in n-octanol/water, and -0.64-0.93 (without DCA) vs. 0.09-1.60 (with DCA) in cyclohexane/water.

Conclusion: These results confirm the usefulness and cost-effectiveness of simple water-organic solvent models in early drug and formulation development.

Objective: Alkaloids from Evodia rutaecarpa exhibit strong antihypertensive and antioxidant effects, but oral administration suffers from low bioavailability. This study aimed to develop and optimize a transdermal gel patch containing a vinegar-water extract of E. rutaecarpa to enhance therapeutic efficacy.

Methods: Gel formulations were optimized using single-factor tests and a Box-Behnken design (BBD), with adhesion and organoleptic properties as evaluation indices. In vitro permeation and kinetic modeling were used to characterize drug release, while antihypertensive effects were assessed in L-NAME-induced hypertensive rats. Serum lactate dehydrogenase (LDH), atrial natriuretic peptide (ANP), estradiol (E2), testosterone (T), and interleukin-6 (IL-6) were quantified by ELISA. Histopathological evaluation of the heart, kidney, and aorta was also performed.

Results: Optimized formulation: NP-700 (6.8 g), DAA (0.15 g), PVP K-90 (0.1 g), tartaric acid (0.15 g), glycerol (25 g), and distilled water (60 g). In vitro, the 72 h cumulative permeation of dehydroevodiamine, evodiamine, and rutaecarpine was 302.64 ± 0.74, 129.11 ± 0.41, and 41.50 ± 0.14 μg·cm^-2, respectively. The release kinetics fitted the Weibull model. In the L-NAME-induced hypertensive rats, patch treatment reduced systolic blood pressure (SBP) from 158.5 ± 4.9 to 122.5 ± 2.5 mmHg (p < 0.001) and significantly restored serum LDH, ANP, IL-6, E2, and T (p < 0.05). Histological analysis showed attenuation of myocardial hypertrophy and fibrosis, endothelial injury and smooth muscle proliferation, and reduced renal edema, tubular atrophy, and inflammatory infiltration.

Conclusions: The E. rutaecarpa vinegar-water extract gel patch exhibited marked antihypertensive activity and protection against target organ damage, highlighting its promise as a novel transdermal therapy for hypertension.

Objective: Tacrolimus is a potent macrolide immunosuppressant widely utilized in solid organ transplantation and the management of autoimmune disorders. The current study aimed to investigate the compatibility of tacrolimus with four commonly used excipients, including sodium croscarmellose, hydroxypropyl methylcellulose (HPMC), magnesium stearate, and lactose monohydrate.

Significance: The design of Experiments transforms drug-excipient compatibility studies by allowing for a precise, data-driven evaluation of multiple key factors with minimal experimental runs, ensuring reliable formulation development while saving time and resources.

Methods: A total of 14 experimental runs were generated using Design-Expert^® software, incorporating three critical variables: temperature, relative humidity (RH), and drug-to-excipient ratio for each excipient. Tacrolimus was blended with the respective excipients at predetermined ratio and subjected to controlled storage conditions under varying temperature and RH levels. Post-incubation, the residual tacrolimus content was quantified via HPLC. Additionally, to further assess physicochemical interactions, DSC and FT-IR were employed for selected samples.

Results: The model-fitting analysis revealed that all excipients, except HPMC, followed a linear pattern, whereas HPMC exhibited quadratic behavior. In all experimental groups, increasing RH significantly accelerated tacrolimus degradation. Notably, elevated temperature and higher excipient ratio further reduced the remaining drug concentration in all formulations except those containing magnesium stearate. The DSC thermograms revealed no significant alterations. FTIR spectroscopic analysis confirmed that only magnesium stearate-containing formulations exhibited distinct spectral patterns compared to pure tacrolimus.

Conclusion: These findings underscore the need for careful consideration when using magnesium stearate in tacrolimus formulations.

Background: Simvastatin, a lipid-lowering drug, has low oral bioavailability due to poor solubility and extensive first-pass metabolism. Transdermal delivery may overcome these limitations.

Objectives: The present study aimed to develop, optimize, and evaluate a simvastatin-loaded transethosomal gel for enhanced dermal permeation and improved antihyperlipidemic efficacy.

Methods: Critical quality attributes, including particle size (PS), entrapment efficiency (%EE), and polydispersity index (PDI), were established through a Quality Target Product Profile. Transethosomes were optimized using a Face-Centered Central Composite Design (FCCCD) by varying Soya phosphatidylcholine and ethanol concentrations. The optimized formulation was characterized using dynamic light scattering, scanning electron microscope, and transmission electron microscope. It was incorporated into a 2% w/v carbopol gel and evaluated for pH, viscosity, and spreadability. In vitro diffusion, ex vivo skin permeation, and skin irritation studies were performed. Antihyperlipidemic efficacy was assessed in high-fat diet-induced hyperlipidemic rats, comparing oral simvastatin (10 mg/kg/day) and transethosomal gel (1 g containing 10 mg simvastatin).

Results: Optimized vesicles showed nanoscale PS (104.9 ± 0.42 nm), high EE (79.92 ± 0.19%), low PDI (0.113 ± 0.45), and negative zeta potential (-32.1 ± 0.48 mV). Microscopy confirmed spherical morphology. The gel exhibited sustained release, good skin compatibility, and significantly improved lipid profile in high-fat diet-fed rats, reducing total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), while elevating high-density lipoprotein cholesterol (HDL-C) compared to oral simvastatin (p < 0.05).

Conclusion: The simvastatin-loaded transethosomal gel demonstrated superior dermal delivery, efficacy, and safety, supporting its potential as a nanoenabled transdermal alternative for hyperlipidemia management.

Objective: To elucidate the application potential of ferritin nanocarriers in targeted cancer therapy, particularly for central nervous system (CNS) tumors (e.g. glioblastoma), focusing on their structural advantages, drug-loading capacity, targeting strategies, and emerging therapeutic directions.

Review significance: Ferritin, leveraging its natural biocompatibility, biodegradability, and unique cage-like structure, is a highly promising drug delivery platform. Its intrinsic ability to specifically bind the tumor-overexpressed transferrin receptor 1 (TfR1/CD71) and penetrate the blood-brain barrier (BBB) provides a unique solution for the precise delivery of chemotherapeutics, metal ions, gene therapy molecules, and novel therapeutics.

Main findings: Ferritin achieves efficient loading of diverse therapeutics (chemotherapeutic agents, metal ions, siRNA) through pH-mediated reassembly, thermally-gated mechanisms, or high hydrostatic pressure methods. Genetic and chemical engineering enhances its intrinsic TfR1/CD71 targeting affinity, significantly improving penetration specificity toward tumor cells and the blood-brain barrier. Successful delivery of regorafenib and immune checkpoint inhibitors to central nervous system tumors has been demonstrated, while combination therapy with ferroptosis inducers or natural bioactive compounds exhibits synergistic efficacy in breast cancer models. Furthermore, ferritin demonstrates potential for multimodal therapeutic integration with ferroptosis induction, photodynamic therapy, and immune checkpoint blockade strategies.

Conclusion: Ferritin nanocarriers exhibit significant advantages for targeted cancer therapy, particularly in blood-brain barrier penetration and precise delivery. Genetic/chemical engineering enhances their efficacy. However, clinical translation faces key challenges: optimizing drug-carrier compatibility, characterizing in vivo pharmacokinetics, and achieving scalable production. Future research priorities include developing smart stimuli-responsive release systems, establishing multimodal therapeutic regimens, and standardizing manufacturing protocols to advance clinical application.

Objective: The Saudi market offers dosages of metformin that have varying release rates and can lead to different pharmacological reactions. Studying formulation bioequivalences helps patients choose the optimum medicine without affecting pharmacological responses.

Significance: This study affects patient care clinically, which can improve Saudi diabetes management by improving efficacy, safety, adherence, access, and cultural relevance.

Method: The bioequivalence and pharmacokinetic parameters were studied using the convolution method. Similarity factor f₁ and different factors f₂ of different types of metformin tablets were calculated. Furthermore, the pharmacokinetic parameters were estimated using the convolution method.

Results: At pH = 6.8 (phosphate buffer) and 50 rpm, 100% of metformin was released within 2 h. While, after two hours in HCl at pH = 1.1 followed by five hours in phosphate buffer at pH = 6.8, 100% of the medication was released after 7 h. The release kinetics showed zero-order kinetics with r² = 0.961 for Formit^® and 0.971 for Glucophage^®, while the release mechanism showed that it follows the Higuchi equation with r² = 0.974 for Formit^® and 0.971 for Glucophage^®, respectively, indicating that the mechanism of drug release was controlled by diffusion. The two brands were lyo-equivalent, with a similarity factor and difference factor equal to 59.36 and 7.26, respectively.

Conclusion: The convolution approach indicated that Glucophage^® and Formit^® have bioequivalent C_max of 601 and 592 ng/ml, respectively. The two products had the same projected T_max of 2.0 h and a modest AUC_∞ differential that did not violate the FDA's 80-125% limit.

Objectives: This study presents a sustainable extraction process for obtaining plant active substances (PAS) from the leaves of Salvia rosmarinus Spenn. (rosemary) and semi-solid microemulsions (SSME) at the same time. The extraction method uses a sustainable solvent system of surfactants, co-surfactants, and water, yielding high PAS miscibility.

Methods: The method was developed using pseudo-ternary phase diagrams, particle size determination and ultrasound-assisted extraction. Optimization was performed via response surface methodology, assessing antioxidant capacity, total phenols, terpenoids, and flavonoids for efficiency evaluation.

Results: Optimal extraction conditions, identified using response surface methodology, which produced SSME with high antioxidant capacity (0.04 to 0.150 mmol/ml) and significant polyphenolic content (0.055 to 0.219 mg of gallic acid/ml). Additionally, the resulting formulations showed a total terpenoid content of 0.04 to 0.150 mmol/ml and a total flavonoid content of 5.4 to 10.5 mg/ml mg quercetin equivalent/ml. The droplet size and polydispersity index values of the optimized extracts were evaluated, yielding mean droplet sizes below 250 nm, indicating the presence of microemulsions. By means of UPLC-ESI-MS/MS the primary PAS were identified, validating the effectiveness of the extraction process in isolating of bioactive compounds with therapeutic potential.

Conclusions: This eco-friendly method not only aligns with green chemistry principles but also supports the development of PAS-rich SSME as candidates for dermal therapies.