RESUMO
Nanotechnology-based chemotherapy is efficient in cancer treatment due to the targeted delivery of small molecules via nano-carriers, which are usually regarded as "inert". However, nano-materials are more preferred as carriers since many cause synergistic anti-tumor effects along with the drug cargo. In this study, a "bioactive" tocopherol succinate (TOS) was grafted to hyaluronic acid (HA) via of disulfide bonds to obtain HA-ss-TOS conjugates which can assemble into nano-micelles but dissociate when exposed to reducing environments in vitro and in vivo. Moreover, paclitaxel-loaded HA-ss-TOS micelles (HA-ss-TOS-PTX) can be efficiently taken up by B16F10 cells overexpressing CD 44, thereafter exhibiting enhanced cytotoxicity. The in vivo imaging study here revealed much greater tumor accumulation of Dir-labeled HA-ss-TOS compared to the free Dir group. In vivo antitumor activities further ensured that the PTX-loaded HA-ss-TOS micelles provided superior antineoplastic responses versus PTX-loaded HA-TOS micelles and Taxol. Moreover, the subcellular dissociated TOS from HA-ss-TOS showed synergistic effects with PTX. These experimental results revealed that reduction-responsive PTX-loaded polymeric nano-micelles with multi-functional properties hold great potential for anti-tumor treatment and, thus, should be further studied.
Assuntos
Dissulfetos/química , Sistemas de Liberação de Medicamentos , Ácido Hialurônico/química , Melanoma Experimental/tratamento farmacológico , Micelas , Paclitaxel/farmacologia , alfa-Tocoferol/química , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/administração & dosagem , Nanopartículas/química , Oxirredução , Paclitaxel/administração & dosagem , Paclitaxel/química , Microambiente TumoralRESUMO
In the present report, we review the technical guidelines and principles on impurity research and control for antibiotics established by various agencies, including the International Conference of Harmonization (ICH), the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the China Food and Drug Administration (CFDA). Progresses with the US Pharmacopoeia (USP), the European Pharmacopoeia (EP) and the Chinese Pharmacopoeia (ChP) to control impurities in antibiotics are also presented. Next, our discussion is focused on analyzing the CFDA's requirements on impurity research and control for antibiotics, and the implementation of ICH, FDA and other technical guidelines for generic drugs impurity control in China. Existing problems are further reviewed, in order to improve the overall process for the control of antibiotic purity.