Drug Development and Industrial Pharmacy最新文献

Objective: Psoriasis is a condition that mostly responds to topical remedies. 5-FU is promising since it is anti-proliferative but has poor permeability. The study aimed to fabricate a novel 5-FU emulgel in order to accomplish enhanced therapy of psoriasis.

Methods: A central composite design (CCD) was employed to optimize the emulgel's key characteristics, including viscosity, spreadability, drug content, and in-vitro release profile. This statistical approach utilized a five-level, two-factor model to construct linear and quadratic relationships between the formulation variables and the desired responses. Design-Expert software version 13 facilitated this process, requiring 13 experimental runs (FU1-FU13) to achieve optimal formulation parameters. The emulgel consisted of an oil phase (oleic acid, Span 80, and Transcutol P) and an aqueous phase (5-FU and Tween 80). High shear homogenization was utilized for emulsification. The emulsion and gel were combined in a 1:1 ratio to form the emulgel. Finally, the optimized emulgel (FU13) underwent assessments for drug-excipient compatibility, ex-vivo drug permeability through the skin barrier, and long-term stability.

Results: The results of optimized formulation FU13 showed viscosity of 5166 ± 9.01 Pa.s, spreadability of 27.56 ± 2.69 g.cm/s, extrudability of 28.49 ± 2.25 g/cm, drug content of 87.9 ± 3.16%, in-vitro drug release of 96.4 ± 1.25 up to 360 min and ex-vivo cumulative permeability of 1056.97 ± 10.33 µg/cm². FU13 showed no significant chemical interactions and was stable throughout stability period.

Conclusion: It is within this context that the present study appears to possess significant potential for topical treatment of psoriasis, as it provides higher therapeutic gain over current treatment modalities with fewer undesired effects.

Objective: This study presents the characterization and evaluation of polyethylene glycol (PEG)-coated liposomal formulations loaded with turmeric (TUR) and cinnamon (CINN) extracts for the treatment of bacterial infections.

Significance: TUR/CINN-loaded PEGylated liposomes enhance the antibacterial effects of TUR and CINN both in vitro and in vivo.

Methods: PEGylated liposomes loaded with TUR and CINN were synthesized using the reverse-phase evaporation method and characterized by dynamic light scattering and spectrophotometry. The formulations were also evaluated for biocompatibility, permeability, and antibacterial efficacy in both in vitro and in vivo environments.

Results: The nanoparticles, with dimensions ranging from 155 to 164 nm, exhibited consistent size distribution (polydispersity index (PDI) of 0.219 to 0.23), stable zeta potentials (-20 to -13 mV), and effective drug encapsulation rates (86.8% to 93.6%), suggesting their potential for targeted drug delivery. In vitro experiments demonstrated their biocompatibility (cell viability exceeding 75% at 40 µg/mL), permeability (transfer rates of 20.2% to 21.5%), antibacterial activity (minimum inhibitory concentrations of 8 to 64 µg/mL), and their ability to generate reactive oxygen species (1.2- to 2-fold increase compared to the control). In an in vivo murine model of Pseudomonas aeruginosa skin infections, significant reductions in viable bacterial counts were observed, with PEG-Lip-TUR/CINN leaving only 10² colony-forming units/mL. Additionally, this formulation displayed anti-metastatic properties, inhibiting cancer cell migration by 99%.

Conclusions: This study highlights the potential of PEGylated liposomal formulations loaded with TUR and CINN as versatile therapeutic platforms for the treatment of antibiotic-resistant infections and cancer metastasis.

Objective: This article provides a substantial review of recent research and comparison on molecular dynamics potentials to determine which are most suitable for simulating the phenomena in graphene-based nanomaterials (GBNs).

Significance: GBNs gain significant attention due to their remarkable properties and potential applications, notably in nanomedicine. However, the physical and chemical characteristics toward macromolecules that justify their nanomedical applications are not yet fully understood. The molecular interaction through molecular dynamic simulation offers the benefits for simulating inorganic molecules like GBNs, with necessary adjustments to account for physical and chemical interactions, or thermodynamic conditions.

Method: In this review, we explore various molecular dynamics potentials (force fields) used to simulate interactions and phenomena in graphene-based nanomaterials. Additionally, we offer a brief overview of the benefits and drawbacks of each force fields that available for analysis to assess which one is suitable to study the molecular interaction of graphene-based nanomaterials.

Result: We identify and compare various molecular dynamics potentials that available for analyzing GBNs, providing insights into their suitability for simulating specific phenomena in graphene-based nanomaterials. The specification of each force fields and its purpose can be used for further application of molecular dynamics simulation on GBNs.

Conclusion: GBNs hold significant promise for applications like nanomedicine, but their physical and chemical properties must be thoroughly studied for safe clinical use. Molecular dynamics simulations, using either reactive or non-reactive MD potentials depending on the expected chemical changes, are essential for accurately modeling these properties, requiring careful selection based on the specific application.

Objective: The increasing prevalence of antimicrobial resistance and the adverse effects associated with systemic administration of antibiotics necessitate the development of alternative therapeutic strategies. The new benzoic acid derivative: (E)-2-(1-isobutyl-2-oxoindolin-3-ylideneamino)-4-chlorobenzoic acid (IOACA) was reported to have a potent activity against Gram-positive bacteria including S. aureus and B. subtilis. That significant activity of IOACA and its log P value of 1.66 prompted us to formulate IOACA as a topical gel for the treatment of skin infections.

Methods: Formulation of a topical gel using Carbopol 934 as gelling agent; physicochemical characterization including drug content, viscosity, spreadability, pH determination, in vitro release study, and release kinetics; in vitro assessment of the antimicrobial efficacy of the gel against Staphylococcus aureus and Bacillus subtilis by agar diffusion method; in vivo evaluation of skin irritation effect and antimicrobial activity of the gel using male albino rat model.

Results: The prepared gel showed homogeneity and consistency. The pH values range from 5.8 to 6.5, with good viscosity and spreadability. The drug content was in an acceptable range. The cumulative amount released of the drug ranged from (72.2 ± 1.3% to 107.6 ± 4.7%). F3 approaches zero-order kinetics. In vivo studies showed significant reduction in viable count and infection severity with complete curing of staphylococcal skin rat infection after eight days of treatment.

Conclusion: The novel benzoic acid derivative-based topical gel is a promising candidate for the treatment of skin infections, offering an effective alternative to systemic antibiotics and contributing to avoid the antimicrobial resistance.

Introduction: Liquisolid (LS) technology is particularly advantageous for poorly water-soluble drugs administered in very low doses because of the improved dissolution rate and superior content uniformity. However, there is a lack of research papers describing the application of this concept on an industrial scale. Thus, we present trials conducted to develop tablets containing 0.5 mg of water-insoluble dutasteride (DTS) according to the LS approach.

Methods: We divided the study into two stages: developing a placebo formulation and producing LS tablets containing DTS on a pilot scale. We tested all the manufactured tablets for mass uniformity, resistance to crushing, disintegration time, dissolution, stability, and presence of impurities.

Results: We demonstrated that a standard high-shear granulator mixer with a spraying system is effective for LS formulation development and transfer to the pilot scale. We were able to compress the system into tablets with the desired assay, content uniformity, dissolution, and mechanical strength.

Conclusion: Multiple operations can be performed on one piece of equipment - that is, pre-mixing a carrier, wetting of the carrier with a solution of an active ingredient in a nonvolatile liquid, mixing of the resulted mass with a coating agent, as well as additional excipients. Preparation of powder blends ready for tableting in line with the one-pot process approach is especially advantageous for the safety of staff engaged in the manufacturing of highly potent drug products.

Background: Prednisolone-derived corticosteroid (PDC) has anti-inflammatory activity in ocular administration. However, drug administration to the eye is extremely difficult due to the complex structure of the eye. Because of the ability of the eye to retain the drug and its physiology, the bioavailability of drugs applied to the eye is very low.

Objective: One of the methods to overcome bioavailability problem is to formulate the drug as a nanoemulsion (NE). NEs are thermodynamically stable, colloidal drug delivery systems. They have small globule size and high surface area. These properties give them the ability to cross the biological membrane and increase the therapeutic efficacy of the drug molecule.

Methodology: The high energy method was used to create an NE eye drop formulation containing PDC, and the effects of changing homogenization processes on NE formation were investigated. After deciding on the optimum formulation; characterization, assay, and in vitro release studies were performed, and the stability of the formulation was followed for 12 months.

Results: The optimum formulation selected initially had 126.6 ± 40.12 nm and 99.9 ± 1.2% PDC, it had 125.4 ± 41.20 nm and 99.29 ± 1.3% PDC after 12 months in 25 °C 40% RH conditions. Cytotoxicity studies have shown no significant cytotoxic effects in NE-containing PDC.

Conclusion: The preparation and optimization of topical NE formulations containing PDC for ocular inflammation treatment were achieved. The developed formulation was stable for 12 months and no toxic effect was found in cell culture studies. This formulation could be useful as an alternative to PDC for ocular applications.

Objective: Amid the escalating global cancer incidence, the development of effective and safe anticancer drugs is a critical priority in medical research. Addressing the clinical shortcomings of ruthenium-based anticancer drugs are currently a prominent focus of research.

Significance and methods: Since the pioneering work with platinum derivatives, significant progress has been made in the fundamental studies of metal complexes for the treatment of a wide range of cancers, and there has been a growing interest in their properties and biomedical applications. Although chemotherapy is crucial in clinical tumor management, platinum(II) anticancer drugs like cisplatin and carboplatin suffer from severe toxicity and drug resistance issues. Among various metal-based drugs, ruthenium(III) complexes are notable for their selectivity, cytotoxic activity in vitro, and effective anticancer properties in vivo. Despite some drug candidates reaching late-stage clinical trials, their clinical application remains constrained by problems such as low solubility, poor stability, and inadequate cellular uptake.

Results: The development of efficient and stable nanocarrier-based drug delivery systems for ruthenium(III) complexes, enhancing pharmacokinetic properties, and enabling slow, controlled release and targeted drug delivery, offers potential solutions to these limitations.

Conclusions: This review delves into the recent strides in nanomaterial-based drug delivery for ruthenium complexes, encompassing research on platinum (II) and ruthenium (III) metal complexes, nano-delivery system designs, and addresses pivotal challenges and future trajectories in this domain.

Objective: In this study, a liposomal gel with anti-inflammatory, antibacterial, and antioxidant effects and improving atopic dermatitis (AD) was prepared using Vaccinium vitis-idaea polyphenol as the main active ingredient, which is safe, effective, of stable quality and has anti-inflammatory and antimicrobial effects.

Methods: The polyphenol extract from Vaccinium vitis-idaea was obtained through ultrasonic extraction and subsequently purified using macroporous resin. A liposome gel incorporating this extract was formulated using poloxamer 188 and poloxamer 407 as the base materials. The gel's physical characteristics, including appearance, vesicle size, and zeta potential, were systematically characterized. Furthermore, its anti-inflammatory, antioxidant, anti-aging, and anti-AD effects were assessed through both ex vivo and in vivo studies.

Results: After process optimization, the yield of Vaccinium vitis-idaea polyphenol was 4.33%; the encapsulation rate of Vaccinium vitis-idaea liposome was 90.45%. The liposome gel prepared by the optimal process had a zeta potential of -33.67 mV, a particle size of 119 nm, a PDI of 0.147, and showed good stability under the conditions of 60 °C, 75% relative humidity, and light intensity of 4500 ± 500 Lux. The results of in vitro studies showed that Vaccinium vitis-idaea polyphenols have antibacterial and antioxidant effects, and the results of in vivo studies showed that the Vaccinium vitis-idaea liposome gel is safe for skin application, effectively reduces dandruff and erythema, reduces the degree of keratinization, reduces the degree of congestion and inflammatory infiltration of local tissues as well as increasing the content of collagen fibers in skin tissues, promotes the restoration of the structural integrity of the skin, and by reducing the inflammatory factors TNF-α, IL-4. By reducing the expression level of inflammatory factors TNF-α, IL-4, IL-13, and MDA, increasing the expression level of SOD, and reducing the diversity of bacterial flora in AD tissues, it can play the role of anti-inflammatory, anti-bacterial, and antioxidant effects and improve the symptoms of AD.

Conclusion: The present study demonstrated that the prepared Vaccinium vitis-idaea liposome gel had an ameliorating effect on AD.

Objective: It has been reported that cancer cells get protected by a complex and rich multicellular environment i.e. the tumor microenvironment (TME) consisting of varying immune cells, endothelial cells, dendritic cells, fibroblasts, etc. This manuscript is aimed at the characteristic features of TME considered as potential target(s) for developing smart anticancer hydrogels.

Significance: The stimuli-specific drug delivery systems especially hydrogels that can respond to the characteristic features of TME are fabricated for treating cancer. For developing anticancer formulations, TME targeting can be considered an alternative way as it enhances the cytotoxic potential and reduces the unwanted effects. This manuscript shall be of quite interest to academicians, researchers, and clinicians engaged in oncology.

Methods: The manuscript was prepared by using the data available in the public domain in online resources such as Google Scholar, PubMed, Science Direct, Scopus, Web of Science, Research Gate, etc.

Results: Smart hydrogels, sensitive to some specific features of TME such as low pH, high concentration of glutathione, specific enzymes, etc., are promising anticancer formulations as these improve the efficacy and lower the side effects of chemotherapy.

Conclusion: The stimuli-responsive hydrogels have been gaining more attention for delivering cytotoxic drugs to the TME in response to specific stimuli. The stimuli-responsive hydrogels, comprising of cytotoxic drug(s) and specific polymers have some special features such as similarity with biological matrix, ability to respond to various internal as well as external stimuli, improved permeability, porosity, biocompatibility, resemblance with soft living tissues, etc.; and are considered as the promising anticancer candidates.

Background: Paracetamol (PAC) overdose causes acute liver injury through oxidative stress, inflammation, and apoptosis. While N-acetyl cysteine (NAC) is the standard treatment, fucoxanthin (FUC), a carotenoid from brown seaweed, has shown hepatoprotective effects in animal studies, but its role in PAC toxicity is unclear.

Objective: Compared to NAC, this study assessed the hepatoprotective potential of oral FUC solution toward PAC-induced injury to the rat's liver.

Method: FUC was formulated as a pharmaceutical solution and characterized via UV-VIS spectroscopy. Six groups of male Wistar rats each contain five animal which are in total 30 rats: negative control (NC), positive control (PC, 2 g/kg PAC), NAC (1200 mg/kg), and three oral FUC doses (100, 200, and 500 mg/kg) for seven days, with PAC administered on day-8. Liver tissues were analyzed for oxidative stress, gene expression, and histology.

Results: FUC solution was clear with absorbance at 433 nm. PAC caused 30% mortality (p < .01 vs. others). NAC reduced ALT (56%), AST (78%), ALP (28%), and increased TP by 25% (p < .001 vs. PC). FUC at 500 mg/kg (F500) was superior, reducing ALT (82%), AST (93%), ALP (40%), and increasing TP (35%) (p < .001 vs. NAC). PAC increased oxidative stress, CYP2E1/CYP3A2 expression, apoptosis markers, and suppressed Nrf2/AMPK/AKT1. F500 improved antioxidants, reduced oxidative stress, and apoptosis, enhanced the Nrf2/AMPK pathway, and downregulated CYP2E1/CYP3A2 (p < .01).

Conclusion: FUC, particularly at 500 mg/kg, offers significant hepatoprotection against PAC-induced liver injury by modulating drug metabolizing enzymes and enhancing antioxidant defenses, warranting further research.