Luracidone hydrochloride exhibits pH-sensitive solubility, which limits its absorption and results in poor oral bioavailability. To address this problem, the present study focused on the formulation of gastro retentive floating pellets of luracidone hydrochloride using the extrusion-speronization technique to enhance gastric retention, solubility, and plasma concentration. The 33 Box-Behnken design was applied to optimize the formulation batch. For that, the levels of HPMC K100 (X1), ethyl cellulose (X2), and spheronization speed (X3) were varied, and their influence was evaluated on aspect ratio (Y1), floating time (Y2), and in vitro % drug release (Y3). The observed optimized batch was subsequently coated with a 5 % ethyl cellulose and subjected to a comprehensive physicochemical evaluation with % drug release and in vivo pharmacokinetic assessment. The drug release data observed that the coated luracidone hydrochloride pellets release the drug over 18 h, whereas the uncoated pellets release up to 12 h. The ethyl cellulose coating also improved the buoyancy, which minimizes dose dumping and improves the absorption window of luracidone hydrochloride in the upper GI tract. The relative oral bioavailability of uncoated and coated pellets was significantly higher, up to 5-fold and 7-fold, respectively, compared to pure luracidone hydrochloride. It strongly supports the hypothesis that coated luracidone hydrochloride gastro retentive floating pellets could enhance oral bioavailability instead of pure lurasidone hydrochloride. Keywords Lurasidone hydrochloride, spheronization, gastro retentive pellets, buoyancy, oral bioavailability
Flavanones represent an important class of naturally inspired scaffolds with diverse pharmacological activities, including notable anticancer potential. Structural modification of the flavanone core offers opportunities to enhance biological performance and identify new lead molecules. In the present study, a series of nine flavanone-arylhydrazone derivatives was synthesised through the condensation of substituted flavanones with corresponding phenylhydrazines under reflux conditions. The synthesised compounds were obtained in good yields and were structurally confirmed using infrared spectroscopy, nuclear magnetic resonance spectroscopy, and mass spectrometry, which collectively verified the integrity of the hydrazone linkage and aromatic substitutions. The derivatives were evaluated for in vitro cytotoxicity against two human breast cancer cell lines, michigan cancer foundation-7 (hormone-dependent) and MDA-MB-231 (triple-negative), using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Tamoxifen served as the reference standard. All compounds exhibited dose-dependent cytotoxicity, with variable responses across both cell lines. Among them, compounds 3 and 1 demonstrated the highest activity, with IC50 values of 33.54±2.2 µM and 36.60±2.4 µM in Michigan cancer foundation-7 cells and 41.08±2.6 µM and 44.21±2.7 µM in MDA-MB-231 cells, respectively. Structure-activity analysis indicated that derivatives bearing electron-withdrawing substituents, such as nitro and halogens, displayed comparatively enhanced potency. The findings emphasise the possible use of flavanone–arylyhydrazone hybrids as promising anticancer candidates. Compounds 3 and 1, in particular, may serve as lead molecules for further mechanistic investigations and optimisation studies aimed at developing new therapeutic agents for breast cancer. Keywords Flavanone, hydrazone, breast neoplasms, Michigan cancer foundation-7 Cells, MDAMB-231 cells
Cerebral toxoplasmosis is a significant cause of morbidity and mortality, especially in immunocompromised individuals, with treatment hindered by poor drug bioavailability in the brain, systemic side effects, and relapse risk. This study aimed to develop an effective nose-to-brain therapeutic strategy using poly (ε-caprolactone) nanoparticles loaded with trimethoprim and sulfamethoxazole and coated with chitosan. Trimethoprim and sulfamethoxazole and coated with chitosan were synthesized, optimized, and coated with 0.5 % CS. Trimethoprim and sulfamethoxazole and coated with chitosan were characterized using analytical techniques, and their in vitro drug release and efficacy against Toxoplasma gondii-infected rat primary astrocytes were evaluated. For in vivo studies, trimethoprim and sulfamethoxazole and coated with chitosan were labeled with IR820, administered intranasally to mice, and their biodistribution was monitored in live animals to assess nose-to-brain delivery. TMP-SMX-NPsCS showed 174 nm, a 0.14 polydispersity index, and +31 mV zeta potential. Encapsulation efficiencies were 88.93 % for TMP and 85.23 % for SMX. FTIR and thermal analysis confirmed uniform drug dispersion and successful CS coating. In vitro drug release studies showed sustained release of both drugs over 24 hours under simulated nasal conditions. trimethoprim and sulfamethoxazole and coated with chitosan treatment maintained 72% cell viability compared to untreated controls. In vivo imaging and ex vivo analysis in mice confirmed brain accumulation and limited systemic distribution of IR820-labeled trimethoprim and sulfamethoxazole and coated with chitosan after intranasal administration. These findings suggest that intranasal delivery of trimethoprim and sulfamethoxazole and coated with chitosan is a promising strategy for expanding the therapeutic arsenal against cerebral toxoplasmosis by enabling direct drug delivery to the brain. Keywords Cerebral toxoplasmosis, trimethoprim, sulfamethoxazole, chitosan, nanoparticles coated with chitosan, intranasal administration, nose-to-brain delivery
Skin cancer is one of the leading and most significant threats to the current scenario, mainly due to global warming occurring across the world. Anticancer drugs either completely kill most cancer cells or, in some ways, modify their growth. However, the selectivity of most medications is constrained, which makes them the most toxic drugs used in therapy. However, technologies and innovations have attracted the attention of contemporary developments with the help of numerous discoveries in nearly every subject. Additionally, vesicular carriers have been explored for drug discovery in a protracted manner. These carriers improve the drug's permeability, ensure that the drug is delivered at the target site and from approaches such as gels and patches, and, for this reason, nullify the troubles related to the distribution, resistance, specificity, selectivity, and systemic toxicity of drugs. This review highlights the etiology, therapies, and briefings of various vesicular carriers for the treatment of skin cancer. Keywords Transdermal drug delivery, carriers, vesicular, skin, cancer
BACKGROUND:The study aimed to analyze the current trends and spatiotemporal dynamics of research on carrageenan and digestive problems through a bibliometric study from 2019 to 2024.MATERIALS AND METHODS:The literature published on carrageenan and digestive issues from the period of January 2019 until July 2024 was examined using an observational and descriptive approach. The use of a quantitative approach was made in relation to authorship distribution and collaboration, country collaboration, and the evolution of themes. A search of the Scopus database was conducted with different keywords of "Carrageenan" and "Digestive problems." Analysis and visualization of the data were done with the use of SciVal and RStudio software.RESULTS:Between 2019 and 2024, a significant increase in publication activity occurred, with associated variations in publication types and pronounced growth in international collaboration. In regard to scientific production, there was an average year-on-year increase of 18.98%, with an average age of the papers of 3.2 years and an average of 15.72 citations per article. A total of 889 authors produced the articles, with an average of 6.71 co-authors per paper and 21.33% international collaborations. Notable institutions producing articles include the Ocean University of China, which produced seven articles, and Jimei University, which produced five articles. The scientific production was highest in China (40), followed by Brazil and Japan, and while most authors contributed a single article, there was a lack of equal scientific productivity accumulated in the articles.CONCLUSIONS:The results highlight both the importance and the need to investigate carrageenan and its impact on digestive issues that might yield exciting avenues of research. The number of publications being produced regarding this foundational aspect of research continues to be relevant. The examination of literature also illustrated the key role of international collaborations and changing research agendas in dealing with the challenges related to digestive problems.
