Drug Development and Industrial Pharmacy最新文献

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.

ObjectivePsoriasis 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 thirteen 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 mins 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.

ObjectiveThe 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.MethodsFormulation 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 rats model.ResultsThe 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 kineticsIn vivo studies showed significant reduction in viable count and infection severity with complete curing of Staphylococcal skin rat infection after 8 days of treatment.ConclusionThe 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.

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.

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: The fabrication of furosemide (FSM) with enhanced oral bioavailability and encapsulation was achieved using a nanostructured lipid carriers (NLCs) drug delivery system.

Significance: The uniform drug distribution is a barrier due to its low dose. The lipid-based delivery system was selected based on its poor solubility and permeability, limiting its poor partitioning and solubility in water-based polymeric delivery systems. The lipophilicity of the FSM makes it favorable to partition with triglyceride-based Compritol 888 ATO and oleic acid with minimized drug expulsion, high drug payload, and sustained release over extended time frames.

Methods: The Organic and aqueous phases of the microemulsion were stabilized using Tween 80, a hydrophilic surfactant. Box-Behnken design-based optimization was done using alteration in various formulation variables to obtain nano-formulation with the lowest particle size and polydispersity, maximal zeta potential and entrapment efficiency.

Results: Design-Expert yielded several optimized formulations with the desirability function. Maximum desirability was obtained at a particle size of around 178 nm, a surface charge of -19.6 mV, and an EE of above 85%.The in vitro release profile depicted 86.5% of cumulative release after 24 h whereas, in vivo pharmacokinetic study revealed an increase in C_max from 0.48 µg/mL (FSM-Suspension) to 0.77 µg/mL (FSM NLCs) to increase the bioavailability to approx. 241% in FSM NLCs. The half-life escalation demonstrated that the residence time of the nanoparticles prolonged at the physiologic pH.

Conclusions: FSM-NLCs exhibited sustained release over a prolonged period, improved residence time in the body, and their action was prolonged.

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.

Objective: The objective of the study was to tackle the recurrence of prostate cancer (PCa) post-surgery and to re-sensitize the docetaxel (DTX)-resistant PC-3 cells to chemo-therapy using NIC.

Significance: Prolonged DTX therapy leads to the emergence of chemo-resistance by overexpression of PI3K-AKT pathway in PCa along with tumor recurrence post-surgery. Suppression of this pathway could be essential in improving the anticancer activity of DTX and re-sensitizing the resistant cells.

Method: Niclosamide (NIC), an anthelmintic drug has shown tremendous anticancer potential and has re-sensitized the resistant cells to various drugs. To mitigate the post-surgical tumor recurrence, an implant-based system facilitating the sustained release of DTX and NIC could be beneficial. DTX and NIC were incorporated within a nanofiber (NF) system to prevent on-site recurrence by local release and re-sensitize the DTX-resistant cells.

Key findings: The fabricated DTX-NIC NF via electrospinning were 334 ± 96.14 nm in diameter and demonstrated sustained release profile till 6 d. Elevated mitochondrial damage, reactive oxygen species levels and apoptotic index revealed improvement in the cytotoxicity of DTX-NIC post incorporation into the NF owing to their sustained release profile. Re-sensitization of PC-3/DTX cells was observed by introduction of NIC which could be due to the suppression of p-Akt1, which was overexpressed in resistant cells.

Conclusion: From superior activity of DTX-NIC NF and re-sensitization of resistant cells, we conclude that DTX-NIC NF could be a beneficial therapeutic regimen in preventing tumor recurrence in PCa.

Background: Tontelea micrantha, a notable plant species, has garnered interest for its medicinal properties, including anti-inflammatory, antibacterial and antiviral effects. A vaccine for Chikungunia virus is still under evaluation and no specific antiviral drug has been licensed to date.

Objective: The work investigated antiviral activity of ethyl acetate (EAEF) and methanolic (EMF) extracts from T. micrantha leaves in mammalian cells exposed to Alphavirus chikungunya (CHIKV).

Methods: The cytotoxicity, antiviral activity, selectivity index, effect on viral gene expression, virus production, and mechanisms of action were evaluated.

Results: EAEF and EMF extracts showed anti-CHIKV effects at non-cytotoxic concentrations, with CC₅₀ above 300 μg/mL, EC₅₀ of 18 and 43 μg/mL respectively, and selectivity Index above 4. These concentrations drastically reduce viral yields and CHIKV gene expression and have shown activity both directly on viral particles and at different stages of the viral cycle.

Conclusion: EAEF and EMF showed robust antiviral activity against CHIKV, making them promising candidates for the development of anti-CHIKV drugs.

Objective: Highly branched poly(β-amino ester) (HPAEs)-based gene therapy holds promise for treating lung cystic fibrosis (CF). However, the translation of HPAEs/DNA nanoparticles into clinical applications poses a significant challenge due to the requirement for high concentrations of the formulation.

Methods: In this work, a straightforward and scalable concentration method was developed for concentrating HPAEs/DNA polyplexes. A series of different buffers with various pH values and ionic components were initially tested to develop the optimized HPAEs/DNA polyplex formulation. Subsequently, the optimized HPAEs/DNA polyplex formulation was concentrated through lyophilization and ultrafiltration.

Results: The ultrafiltration outperformed the lyophilization in concentration capacity, showing a 24-fold increase in the concentrated formulation compared to the original non-concentrated formulation. The concentration does not disturb the transfection efficiency in lung CF epithelial cells, indicating its potential for lung delivery applications. Moreover, the concentrated HPAEs/DNA polyplex successfully restored the production of CF transmembrane conductance regulator (CFTR) protein in primary lung CF epithelial cells, surpassing the performance of the non-concentrated common gene transfection reagents such as Lipofectamine 3000 and Xfect.

Conclusion: The concentrated HPAEs/DNA formulation represents a promising step forward for preclinical testing (e.g. in vivo evaluation), with further research needed to confirm its potential for clinical use.