Current Issue : April - June Volume : 2019 Issue Number : 2 Articles : 5 Articles
(1) Background: Monoclonal antibodies are used in the treatment of multiple conditions\nincluding cancer, autoimmune disorders, and infectious diseases. One of the initial steps in\nthe selection of an antibody candidate for further pre-clinical development is determining its\npharmacokinetics in small animal models. The use of mass spectrometry and other techniques to\ndetermine the fate of these antibodies is laborious and expensive. Here we describe a straightforward\nand highly reproducible methodology for utilizing radiolabeled antibodies for pharmacokinetics\nstudies. (2) Methods: Commercially available bifunctional linker CHXAâ? and 111Indium radionuclide\nwere used. A melanin-specific chimeric antibody A1 and an isotype matching irrelevant control\nA2 were conjugated with the CHXAâ?, and then radiolabeled with 111In. The biodistribution was\nperformed at 4 and 24 h time points in melanoma tumor-bearing and healthy C57BL/6 female mice.\n(3) The biodistribution of the melanin-binding antibody showed the significant uptake in the tumor,\nwhich increased with time, and very low uptake in healthy melanin-containing tissues such as the\nretina of the eye and melanized skin. This biodistribution pattern in healthy tissues was very close\nto that of the isotype matching control antibody. (4) Conclusions: The biodistribution experiment\nallows us to assess the pharmacokinetics of both antibodies side by side and to make a conclusion\nregarding the suitability of specific antibodies for further development....
Psoriasis is a chronic autoimmune systemic disease with an approximate incidence of 2%\nworldwide; it is commonly characterized by squamous lesions on the skin that present the typical\npain, stinging, and bleeding associated with an inflammatory response. In this work, poly(methyl\nvinyl ether-alt-maleic ethyl monoester) (PMVEMA-ES) nanofibers have been designed as a delivery\nvehicle for three therapeutic agents with palliative properties for the symptoms of this disease\n(salicylic acid, methyl salicylate, and capsaicin). For such a task, the production of these nanofibers\nby means of the electrospinning technique has been optimized. Their morphology and size have\nbeen characterized by optical microscopy and scanning electron microscopy (SEM). By selecting the\noptimal conditions to achieve the smallest and most uniform nanofibers, approximate diameters of\nup to 800â??900 nm were obtained. It was also determined that the therapeutic agents that were used\nwere encapsulated with high efficiency. The analysis of their stability over time by GC-MS showed\nno significant losses of the encapsulated compounds 15 days after their preparation, except in the\ncase of methyl salicylate. Likewise, it was demonstrated that the therapeutic compounds that were\nencapsulated conserved, and even improved, their capacity to activate the transient receptor potential\ncation channel 1 (TRPV1) channel, which has been associated with the formation of psoriatic lesions....
The present study was carried out to investigate the potential of cationic functionalization\non imatinib nanocrystals to improve the mucoadhesiveness and, thus, delivery to the lesion\nof cervicovaginal tumors. Amino-group-functionalized imatinib nanocrystals (NC@PDA-NH2)\nwere prepared with near-spheroid shape, nanoscale size distribution, positive zeta potential,\nand relatively high drug content with the aid of the polydopamine-coating technique. Efficient\ninteraction between NC@PDA-NH2 and mucin was proven by mucin adsorption which was related\nto the positive zeta-potential value of NC@PDA-NH2 and the change in the size distribution\non mixing of NC@PDA-NH2 and mucin. Cellular uptake, growth inhibition, and apoptosis\ninduction in cervicovaginal cancer-related cells demonstrated the superiority of NC@PDA-NH2 over\nunmodified nanocrystals. For practical intravaginal administration, NC@PDA-NH2 was dispersed in\nPluronic F127-based thermosensitive in situ hydrogel, which showed suitable gelation temperature\nand sustained-release profiles. In comparison with unmodified nanocrystals, NC@PDA-NH2\nexhibited extended residence on ex vivo murine vaginal mucosa, prolonged in vivo intravaginal\nresidence, and enhanced inhibition on the growth of murine orthotopic cervicovaginal model\ntumors indicated by smaller tumor size, longer median survival time, and more intratumor\napoptosis with negligible mucosal toxicity. In conclusion, cationic functionalization endowed\nNC@PDA-NH2 significant mucoadhesiveness and, thus, good potential against cervicovaginal cancer\nvia intravaginal administration....
Cyclosporine (CsA) has a selective property of suppressing various T-lymphocyte functions.\nThis is of utmost importance in preventing allograft rejection by several organ transplantations,\nas well as in the treatment of systemic and local autoimmune disorders. However, the poor water\nsolubility of CsA can be a major hurdle for its absorption into the blood stream, which leads to low\nbioavailability and thus less efficacy. The aim of this study was to prepare, characterize, and evaluate\nin vitro as well as in vivo, the potential of the innovative CsA drug delivery system. The latter\ncontains CsA in spherical amorphous solid dispersion (SASD) which is embedded in an original............
In this study, we prepared an injectable drug delivery depot system based on a visible\nlight-cured glycol chitosan (GC) hydrogel containing paclitaxel (PTX)-complexed beta-cyclodextrin...............
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