Pharmaceutical Development and Technology最新文献

Topical muscle relaxants are gaining interest in pharmaceuticals. Dantrolene sodium (DS), an FDA-approved relaxant targeting ryanodine receptors, is limited in topical use by poor physicochemical properties, delayed onset, and hepatotoxicity. This study introduces the first optimized hyalubilosome-based nanocarrier for non-invasive DS delivery. Two anionic surfactants were used as edge activators to improve drug encapsulation and permeation. The optimized nanocarrier had a spherical shape, 165 nm particle size, -31.2 mV zeta potential, and 97.47% entrapment efficiency. Ex vivo studies showed superior permeation compared to DS suspension (10% in water, pH 6.8), with 30% of the dose permeating within 15 min. In vivo, efficacy was tested in Wistar mice using the Straub tail test with a single 30 mg/kg topical dose. Behavioral analysis showed a fivefold increase in muscle relaxation vs. untreated controls (p < 0.0001). The formulation had an onset within one minute and complete relief within two minutes, unlike the conventional topical DS, which showed no effect for 90 min. This highlights hyaluronic acid-based transbilosomes as a promising nanoplatform for fast, effective topical DS delivery and potential muscle spasm treatment.

Abiraterone acetate (ABT) is an androgen biosynthesis inhibitor approved for the treatment of prostate cancer. However, the treatment course of ABT is constrained by its high dose, poor solubility and permeability issues. A solid supersaturated self-nanoemulsifying drug delivery system (ssSNEDDS) is an excellent approach for improving drug loading. The aim was to increase the solubility and drug loading of ABT in SNEDDS via supersaturation by using a polymeric precipitation inhibitor (HPMC E5). Liquid SNEDDS were thoroughly optimized with a mixture design followed by solidification with Aerosil^® 200 by the adsorption method. The developed ABT-ssSNEDDS showed a nano-ranged particle size of 106.23 ± 4.15 nm and PDI of 0.234 ± 0.0069. Furthermore, the powder showed an angle of repose of 34.86 ± 0.30° indicating good flow properties with smooth morphology under SEM analysis. DSC and PXRD studies revealed amorphization of ABT in the ABT-ssSNEDDS group. Furthermore, the dissolution study demonstrated significantly higher ABT release from ABT-ssSNEDDS in comparison to free ABT after 2 h in pH 1.2 and 6.8 pH buffer. In-vitro cell culture studies in the PC-3 cell line denoted significantly enhanced anticancer activity and cellular uptake. Thus, ABT-ssSNEDDS could be an encouraging approach for improved oral therapy and enhanced drug loading of ABT.

The authors carried out a comprehensive review of the application of peptides known as cell-penetrating peptides (CPPs) in various drug delivery systems (DDS), with the prospect of achieving novel solutions and ideas to overcome the challenges of DDS, by making them more able to penetrate cells and biological membranes. A conceptual search was conducted in relevant literature databases (Scopus, PubMed, Web of Science, and Google Scholar) up to 1 April 2025 using keywords such as drug delivery systems, cell-penetrating peptides, CPPs, complexes, conjugates, nanoparticles, dendrimers, exosomes, liquid crystalline, liposomes, micelles, nanospheres and lipid nanoparticles. The studies demonstrate that the antimicrobial effect of drugs, including curcumin, gentamicin, and antifungal drugs like imidazoacridinone derivatives, can be enhanced when they are conjugated or complexed with CPPs. CPPs possess positive charges, which make them suitable for gene therapy applications by facilitating the delivery of plasmids and siRNAs with negative charges in modern delivery systems. Medicinal formulations containing CPPs in combination with liquid crystals or nanostructured lipid carriers (NLCs) increase drugs penetration to the skin. Additionally, several investigations showed that CPPs could have a positive impact on the pharmacokinetic and pharmacodynamic of chemotherapy agents, reducing their side effects. CPPs have significant potential in enhancing penetration, bioavailability, targeting, and optimization of DDS. By using computer modeling and designing CPPs with more desirable features and conducting more clinical studies, new methods for treating diseases and better formulations can be achieved.

Sulpiride (a model class IV drug) is a central dopamine antagonist, that is commonly used in the treatment of various psychiatric and gastrointestinal conditions. However, its poor aqueous solubility and low oral bioavailability (20-30%) limit its therapeutic efficacy. Electrospun nanofibers offer a promising method to enhance the oral absorption of poorly water-soluble drugs. This study, for the first time, aimed to investigate the feasibility of electrospun Eudragit S100-loaded Sulpiride nanofibers as an enhanced oral delivery system, compared to drug-loaded solid dispersion. The physicochemical properties of the nanofibers were characterized. The drug's intestinal permeability was evaluated using an ex vivo non-everted sac technique. Sulpiride-loaded nanofibers exhibited uniform morphology with a very narrow nanosize range of (98.4-123.6 nm) and a high drug-loading efficiency of >98%. In vitro, dissolution demonstrated a significant enhancement in the Sulpiride's dissolution rates from the nanofiber formulations (>94% of the drug released within 4 h) compared to the solid dispersion formulation (˂77% of the drug released). The nanofiber formulations exhibited a 2-fold increase in the drug's intestinal permeability and a 4-fold increase in apparent permeability (Papp) compared to the free drug. The improved dissolution and intestinal permeability of Sulpiride-loaded nanofibers suggest their potential application for enhancing the oral delivery and therapeutic efficacy of class IV drugs.

Transfersomes (TFS) are deformable vesicles, known for their ability to enhance transdermal drug penetration. This study aimed to evaluate whether TFS can also enhance ocular delivery of poorly soluble tonabersat. TFS were prepared using Phospholipon^® 90G with Tween^® 80 as the edge activator. The effect of formulation parameters (edge activator and cryoprotectant concentrations) on TFS characteristics were evaluated using a full factorial design. The optimized TFS eyedrop was characterized for particle size, zeta potential, deformability, entrapment efficiency (EE), drug content, pH, osmolality and TFS stability over 3 months at different storage conditions. Furthermore, drug penetration into the cornea, conjunctiva, eyelid, and sclera-choroid after topical application was studied ex vivo using a tonabersat solution in medium chain triglycerides as the control. The optimized TFS formed spherical unilamellar vesicles with a mean diameter <130 nm, EE >80%, and were stable at -20 and 5 ± 3 °C for up to 3 months. The TFS eyedrop resulted in significantly greater ocular penetration than the control without affecting the barrier properties of the tested tissues. Drug penetration into different ocular tissues was compared, shedding light on the penetration mechanism of TFS. Overall, this study demonstrates that TFS provide a promising alternative for the ocular delivery of tonabersat.

Regulating hemorrhage is crucial during dental procedures, particularly surgical interventions where substantial blood loss may occur. Hemostatic sponges are effective instruments for controlling hemorrhage, facilitating hemostasis, preparing the surgical area, and enhancing the healing of injuries. This work aimed to present a novel hemostatic sponge created by integrating antihemorrhagic chemicals with the natural polysaccharide tragacanth. Gum tragacanth (GT) (derived from the species Astragalus gossypinus) was solubilized in water and combined with nanoclay (NC) and tranexamic acid (TXA) at varying doses. Subsequently, they were freeze-dried in cubic silicone molds. Scanning electron micrographs revealed that the incorporation of TXA and NC significantly increased the porosity of the sponges. No evidence of chemical bonding was present in our converted infrared spectra. Prothrombin time (PT), activated partial thromboplastin time (aPTT), and whole blood coagulation index showed improvement with the administration of hemostatics, with TXA demonstrating a more pronounced impact. The cytotoxicity assay of the hemostatic GT exhibited no notable difference from the control sample. The hemostatic GT has demonstrated significant potential for medical applications, particularly in dentistry, and applies to procedures such as endodontics and prosthesis placement.

The purpose of this study was to investigate the impact of glycyrrhizic acid (GL) concentrations on in vitro and in vivo behavior of quercetin (QT) nanocrystals stabilized by GL (QT-NCs/GL), with a particular focus on its influence on liver targeted drug delivery. QT-NCs/GL with similar particle size around 200 nm were successfully prepared by media milling technique using different concentrations of GL, which were 10%, 20% and 40% (w/w) of the QT. All QT-NCs/GL showed oval and rod shapes, and remained in crystalline state with a reduced crystallinity as GL concentrations increased. All QT-NCs/GL exhibited significant solubility increase and drug release improvement of QT as compared to raw QT. Pharmacokinetics revealed similar plasma concentration-time profiles of QT after intravenous of all QT-NCs/GL. All QT-NCs/GL exhibited rapidly distribution of QT to liver with the maximum QT concentration more than 750 μg/g at 5 min after intravenous administration, and the AUC0∼t of QT for three formulations in liver were significant difference with the following order: QT-NCs/GL-40% > QT-NCs/GL-20% > QT-NCs/GL-10%. These results suggested that different GL concentrations exhibited significant influence on liver targeted delivery of QT-NCs/GL, and more GL used in QT-NCs/GL may contribute more liver distribution of QT.

Metformin is the most common drug used in patients with type 2 diabetes. Our aim is to assess if the in vitro dissolution of Metformin IR 500 mg tablets and its kinetics is altered in the presence of various medication swallowing lubricants used in vivo and to evaluate their rheological properties of tablet lubricant. The dissolution profile of metformin tablets (crushed and whole) mixed with selected medication swallowing lubricants was studied in a Distek^® Dissolution apparatus at 6 different time points (n = 5). Samples were diluted and analysed using a UV-visible Spectrometer at a wavelength of 232 nm using a calibrated absorbance-concentration curve. Dissolution data will be modelled to understand the effect on its dissolution kinetics. Rheology studies were completed using an AR G2 System Rheometer. Gloup^® Forte delayed the in vitro dissolution of metformin from crushed or whole tablets and produced lower peak concentrations, irrespective of the pH of the dissolution media (reduction up to 35% reduction in concentration in pH = 6.8). Gloup^® Forte has changed the release to almost erosion-controlled in different media when mixed with crushed metformin tablets. Further studies evaluating the effects of commonly used thickened fluids on medication may be required to better inform clinical practice.

This study was conducted to develop a lycopene-carrier solid dispersion-loaded lipid liquid crystal nanoparticle (LLC) formulation aimed at enhancing aqueous solubility, bioavailability, and wound healing efficacy. Lycopene was extracted from tomato paste using the Soxhlet method and was formulated into solid dispersions with polyvinylpyrrolidone (PVP) and Poloxamer (Plx) to enhance the solubility of lycopene. The physicochemical properties of the solid dispersion products were characterized. Cytotoxicity on human fibroblast cells, cell migration, and wound healing treatment in the mice were also assessed. PVP demonstrated greater efficacy in enhancing the aqueous solubility of lycopene than Plx. The results indicated that the morphology of the LLC was cubosome, achieving a high encapsulation efficiency of 71.57 ± 2.1%. The LLC formulations demonstrated significantly enhanced release rates of 68.18 ± 1.78% and improved skin permeation compared to the lycopene solid dispersion solution. The results of the cell culture demonstrated the safety of the formulation, and the in vitro scratch test showed the migration of fibroblast cells in the presence of the lycopene-PVP solid dispersion loaded LLC compared to lycopene alone. Based on the obtained results, it can be concluded that the proposed formulation (lycopene-PVP solid dispersion loaded LLC) could be a suitable option for wound healing.

The pandemic caused by the SARS-CoV-2 virus has led scientists to intensify research on antiviral drugs and vaccines. As a result of these studies, it was observed that molnupiravir (MLP) and peramivir (PRV) could be used against pandemic. MLP affects SARS-CoV-2 replication, but it necessitates high doses, which can cause adverse effects in patients. PRV is a neuraminidase inhibitor, but the bioavailability of the drug after oral administration is very low. In this study, MLP-, PRV-loaded and combined liposome (COMB-Lipo) formulations were prepared via the thin film hydration method. Phospholipon 90 G-based formulations exhibited the most favorable characteristics, with a particle size of 111-145 nm, a polydispersity index (PDI) of less than 0.4, and a zeta potential (ZP) of 6-12 mV). Cell culture studies demonstrated that developed stable formulations are nontoxic to L929 and Vero E6 cells. Antiviral activity assessments against SARS-CoV-2 suggested the effectiveness of liposomes in inhibiting viral activity. These findings demonstrate that a possible synergistic effect of the newly developed sustained-release COMB-Lipo formulation is suggested with the complementary antiviral mechanisms of the combined agents. As a result, the therapeutic potential of co-delivery of anti-SARS-CoV-2 drugs for pulmonary application is considered a promising approach for long-acting treatment of COVID-19.