Pharmaceutical Development and Technology最新文献

Purpose: This work aimed to develop fenbendazole nanocrystals to evaluate their effects on the energetic metabolism of Taenia crassiceps cysticerci, following an intracranial inoculation in mice.

Methods: Fenbendazole was nanoformulated by the antisolvent method using poloxamers 188 and 407 as stabilizers. The nanosuspensions were lyophilized without cryoprotectants and the nanocrystals were characterized in terms of particle size, zeta potential, and dissolution performance. The in vivo study was performed in infected animals treated with nanoformulated fenbendazole and raw drug and their metabolic impact was quantified by analyzing specific metabolites.

Results: Fenbendazole samples were obtained by nanoprecipitation in > 80% yield. The average particle size of the freeze-dried samples was between 372 nm and 1600 nm. The nanosystems released a greater amount of the drug into the solution, compared to the raw drug. The in vivo studies showed that the fenbendazole-treated groups induced gluconeogenesis, partial blockage of the TCA cycle, and increased protein catabolism. As seen, the nanoformulation presented a greater effect on these parameters than the raw drug leading to remarkable modifications in the metabolism of the parasite, which in turn can influence the overall course of the infection and treatment outcomes.

Conclusion: These findings suggest that nanoformulated fenbendazole may be considered a valuable approach for an effective treatment of neurocysticercosis.

This study aimed to provide an alternative and effective delivery system to combat polymyxin B (PMB) toxicity and bacterial resistance through inhalation therapy. PMB was formulated as liposomal dry powder for inhalation using thin-film hydration and spray-dried methods. PMB formulations were characterized physically. The aerodynamic properties were determined using next-generation impactor (NGI). In vitro drug release was done in a phosphate buffer pH 7.4 for 2 h. Cytotoxicity was evaluated by the MTT cell viability assay. Antimicrobiological activities were done using bioassay and flow cytometry. Particle sizes of the spay-dried formulations were between 259.83 ± 9.91 and 518.73 ± 27.08 nm while the zeta potentials ranged between 3.07 ± 0.27 and 4.323 ± 0.36 mV. The Fourier-transform infrared spectroscopy shows no interaction between PMB and other excipients. Differential scanning calorimetry thermograms revealed amorphousness of the formulated powders and SEM revealed spherical PMB formulations. Similarly, mass media aerodynamic diameter results were 1.72-2.75 nm, and FPF was 25%-26%. The cumulative release of the PMB formulations was 90.3 ± 0.6% within 2 h. The killing kinetics revealed total cell death at 12 and 24 h for Pseudomonas aeruginosa and Escherichia coli, respectively. The PMB inhalation liposome showed better activity and was safe for lung-associated cell lines.

Formononetin (FNT) has limited application due to poor water solubility and substantial phase II metabolism. In the present study, we used phospholipid complex (PC) containing FNT and UDP-glucuronosyltransferase (UGT1A1) inhibitor piperine (PIP) to overcome FNT limitations. We characterized and compared both FNT-PC and FNT-PIP-PC complexes. Our data showed both groups improved FNT water solubility and oil-water partition coefficient. NMR, DSC, and SEM were performed to identify the interaction and the geometrical nature of complex. When compared, FNT-PIP-PC released more FNT in in vitro release and permeation through Caco-2 monolayer than FNT-PC and pure FNT. In vitro data was consistent with the in vivo pharmacokinetic profile that showed increased, C_max and AUC_(0-24) by 7.16 and 23.33-fold and 29.65 and 23.33-fold at 5 and 10 mg/kg in FNT-PIP-PC, compared to pure FNT. Additionally, co-treatment of PIP and FNT improved in vitro pharmacological action in dexamethasone-induced osteoporosis. Thus, our study showed addition of PIP in FNT-PC further increases FNT water solubility and protects it from phase II metabolism, leading to enhanced bioavailability with improved pharmacological activity.

The European Medicine Agency has approved canagliflozin (CGF) drug to improve glycemic control in patients with type II diabetes. Our study aimed to enhance the solubility and pharmacokinetics of canagliflozin. Since crystalline canagliflozin is insoluble in water, its absolute bioavailability is less than 65%. Gelucire 50/13 was used as a lipid-based drug carrier to create solid dispersions of canagliflozin. SEM, PXRD, and DSC analysis all pointed to canagliflozin as having a crystal structure. Fusion and solvent evaporation methods were used to prepare the solid dispersions. In solid dispersions, the medication was found to be amorphized according to SEM, DSC, and PXRD studies. The water solubility of canagliflozin increased significantly by 11-23 fold using the solvent evaporation approach and by 12-25 fold using the fusion method. The pharmacokinetic parameters are improved at higher concentrations of gelucire. With pure canagliflozin, the AUC values climbed over 4 h (t_max) to 23440 µgh/mL, while with GDF 1:7, they grew to 52217. Gelucire 50/13 is an excellent option as a biomaterial carrier for drug delivery systems that use solid dispersion because it enhances biological membrane penetration. By dispersing the canagliflozin and gelucire, bioavailability may be enhanced by the fusion process that achieves molecular binding.

Aim: Oral candidiasis is often challenging due to limited effectiveness of topical treatments. This study aimed to develop novel caspofungin formulations for administration onto the oral mucosa to enhance drug retention and efficacy.

Method: Five caspofungin (2%, w/v) formulations were developed to assess their permeability, retention and mucoadhesiveness. Ex vivo permeability assays were performed on buccal and sublingual mucosae, and histological analyses conducted to evaluate tissue tolerance.

Results: Formulation composed of chitosan demonstrated the highest retention in both buccal (5183.24 ± 587.32 µg/cm²) and sublingual (1090.72 ± 110.26 µg/cm²) mucosae. Other formulations exhibited significantly lower retention, ranging from 7.53 ± 0.81 to 1852.10 ± 193.24 µg/cm² in buccal mucosa and 1.64 ± 0.14 to 317.74 ± 31.78 µg/cm² in sublingual mucosa. Chitosan-based formulation exhibited the highest mucoadhesive strength, with values of 5179.05 ± 31.99 mN/cm² for buccal and 7026.10 ± 123.41 mN/cm² for sublingual mucosae, and also superior extensibility, which facilitates application in the oral cavity. All formulations showed antifungal activity against Candida spp., and histological analyses revealed minor epithelial alterations.

Conclusion: The developed formulations offer distinct advantages for treating oral candidiasis, with chitosan formulation emerging as the most promising due to its superior retention, mucoadhesion force, and spreadability, making it a potential candidate for further clinical investigation.

Traditional chemotherapeutic drugs lack optimal efficacy and invoke severe adverse effects in cancer patients. Polydatin (PD), a phytomedicine, has gradually gained attention due to its antitumor activity. However, its low solubility and poor bioavailability are still cornerstone issues. The present study aimed to fabricate and develop hyaluronic acid/lactoferrin-double coated PD/PLGA nanoparticles via a layer-by-layer self-assembly technique for active targeting of CD44 receptors in lung cancer. Different molecular weights (M.wt.) of HA (32 and 110 kDa) were exploited to study the relationship between the HA M.wt. and the NPs targeting efficacy. The optimized formulations were fully characterized. Their cytotoxicity and cellular uptake were investigated against A549 cell line by CCK-8 kit and fluorescence imaging, respectively. Finally, HA110/Lf-coated PD/PLGA NPs (F9) were subjected to a competitive inhibition study to prove internalization through CD44 overexpressed receptors. The results verified the fabrication of F9 with a particle size of 174.87 ± 3.97 nm and a zeta potential of -24.37 ± 1.19 mV as well as spherical NPs architecture. Importantly, it provoked enhanced cytotoxicity (IC₅₀ = 0.57 ± 0.02 µg/mL) and superior cellular uptake efficacy. To conclude, the current investigation lays the foundation for the prospective therapeutic avenue of F9 for active targeting of CD44 receptors in lung cancer.

The electrospinning method involves the production of different drug delivery systems using various polymers. The production of proliposomes with electrospinning provides the hybridization of two novel drug delivery systems. Retinoic acid, also known as all-trans retinoic acid (ATRA), is a common and effective drug for acne therapy. This study aimed to prepare ATRA-loaded proliposomal nanofibers and evaluate their effectiveness on microbial biofilm inhibition. Blank and ATRA-loaded proliposomal nanofiber formulations were fabricated in various polyvinylpyrrolidone, phosphatidylcholine and cholesterol ratios. TEM images verified the rapid formation of the liposomes after the hydration of nanofibers. The vesicle size, polydispersity index and zeta potential values of self-assembled liposomes were measured. The vesicle size values were found to be 321.9-363.8 nm with PDI values varying between 0.332 and 0.511 and zeta potential values of (-16.8) to (-20.5)mV. ATRA-loaded proliposomal nanofibers provided higher bioadhesion (0.25 mJ/cm²) than the commercial cream (0.07 mJ/cm²). The short-term stability results showed that the initial characteristics remained for three months at 4 °C. The proposed ATRA-loaded self-assembled proliposomal system provided antibacterial, fungistatic or fungicidal effects superior to retinoic acid itself and inhibited biofilm formation in lower concentrations. This approach can combine the stability advantage of nanofibers in the dry state with the high effectiveness of liposomes in acne treatment presenting antibacterial and anti-biofilm-forming activity against Candida albicans and Cutibacterium acnes.

Introduction: The present study evaluates the sticking propensity of Uncoated steel, and chromium nitride (CrN), zirconium nitride (ZrN), titanium nitride (TiN) and Ultracoat punch coatings during the tableting process of microcrystalline cellulose (MCC) conducted on a Manesty^® F3 single station tableting press.

Methods: Surface properties including surface roughness, surface free energy (SFE) and its components, the atomic percentage of surface polar functional groups and oxides measured with X-ray photoelectron spectroscopy were used to characterize the surface propensity to sticking.

Results: After five hours of tablet pressing, MCC powder particles were found to adhere to the TiN coated and the uncoated steel punches. Surface analysis show that surface roughness of all the tested punches was similar. The Lewis base SFE component (LB-comp) was found to govern the acid-base interactions of the tested surfaces, and its value was higher for punch surfaces affected by sticking. The surfaces exhibiting higher LB-comp are more prone to strong acid-base interactions with water molecules that evaporate from the powder bed during compression. Therefore, these surfaces adsorbed water and allow sticking through capillary adhesion force.

Conclusion: The total atomic percentage of the surface polar functional groups (PFG) and oxides was also high for the surfaces that stick to MCC during tableting, suggesting that hydrophilic molecules on the punch surface favor sticking.

Asthma and Chronic Obstructive Pulmonary Disease (COPD) are major global health concerns, with inhalation therapy being a primary treatment method. Dry powder inhalers (DPIs) often face challenges related to particle aggregation, which can diminish drug delivery efficiency. This study investigates particle aggregation and aims to optimize the cohesion-adhesion balance to improve inhalation efficiency. Advanced techniques like atomic force microscopy and Raman imaging were used to analyze particle interactions, focusing on lactose ratios, particle morphology, and drug-drug interactions. The therapeutic efficacy of optimized formulations containing budesonide (BUD) and Arformoterol (AFT) was assessed using an asthma model, showing significant improvements in sRAW, neutrophil count, and tidal volume compared to the positive control, with p-values below 0.01. AFT exhibited comparable efficacy to Formoterol at half the dose. Additionally, pharmacokinetic studies demonstrated similar in vivo behavior between the drugs, confirming the therapeutic advantage of AFT, with p-values for AUC_0-t and Cmax of .646 and .153, respectively. The fine particle fractions for AFT and BUD were 39.4% and 50.6%, respectively, indicating improved drug delivery efficiency and potential for better clinical outcomes in asthma and COPD patients.

The extent and rate of release of active substances from topical products must be sufficient to ensure their effectiveness, which depends on selecting the most appropriate formulation. This study examined allantoin emulsions and gel formulations. In water-in-oil (W/O) and oil-in-water (O/W) emulsions, the main emulsifier was varied, while the same gelling agent was used in all formulations to test the effects of oil phase presence and emulsifier type on allantoin release, as well as the formulations' rheological and textural characteristics. O/W emulsions exhibited similar release rates and the overall amount released over six hours (11-14.8%), while the highest amount of allantoin (20.9%) was released from the gel formulation. Conversely, the amount of allantoin released from the W/O emulsion (0.77%) was insufficient. Experimental data generally fit best with the Higuchi model kinetics. The formulations demonstrated shear-thinning thixotropic behavior. The greatest deviation from the Newtonian type of flow, with the smallest value of constant n (0.106-0.13) and the largest thixotropic loop area (6602.67-8140 Pas^-1) were shown by O/W emulsions. The W/O emulsion exhibited the highest constant n (0.70) and smaller hysteresis area (991.23 Pas^-1). Firmness and consistency values increased in the order: gel < W/O emulsion  < O/W emulsions. The O/W emulsions showed similarity in microstructure and textural characteristics, likely explaining their similar release behavior.