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In this work, we developed a novel active targeting and pH-responsive system for delivering the drug doxorubicin (DOX) to tumor sites using folic acid (FA)-modified multiwalled carbon nanotubes (MWCNTs). Acid-treated MWCNTs with carboxyl groups were first covalently conjugated with polyethyleneimine (PEI). Subsequent sequential modification with FA (via a polyethylene glycol spacer), fluorescein isothiocyanate (FI), and acetic anhydride/triethylamine resulted in multifunctional FA-bound MWCNT (MWCNT-PEI.Ac-FI-PEG-FA) nanomaterials that possessed exceptional colloidal stability and good biocompatibility in a given concentration range. The FA-bound MWCNTs were characterized using various techniques and exhibited a high drug loading and an encapsulation efficiency as high as 70.4%. DOX/MWCNT-PEI.Ac-FI-PEG-FA nanocomplexes (DOX/MWCNT NCs) exhibited pH-responsive release in acidic environments. Importantly, the DOX/MWCNT NCs targeted tumor cells overexpressing FA receptors (FARs) and effectively inhibited their growth. In vivo anticancer experiments demonstrated that DOX/MWCNT NCs not only enhanced the suppression of tumor growth but also decreased the side effects of free DOX. The developed FA-modified MWCNTs with an unconventionally high DOX loading boosted in vivo anti-tumor efficacy, and the lower systemic toxicity may be utilized for tumor therapy upon clinical translation. [ABSTRACT FROM AUTHOR]

In this work, we developed a novel active targeting and pH-responsive system for delivering the drug doxorubicin (DOX) to tumor sites using folic acid (FA)-modified multiwalled carbon nanotubes (MWCNTs). Acid-treated MWCNTs with carboxyl groups were first covalently conjugated with polyethyleneimine (PEI). Subsequent sequential modification with FA (via a polyethylene glycol spacer), fluorescein isothiocyanate (FI), and acetic anhydride/triethylamine resulted in multifunctional FA-bound MWCNT (MWCNT-PEI.Ac-FI-PEG-FA) nanomaterials that possessed exceptional colloidal stability and good biocompatibility in a given concentration range. The FA-bound MWCNTs were characterized using various techniques and exhibited a high drug loading and an encapsulation efficiency as high as 70.4%. DOX/MWCNT-PEI.Ac-FI-PEG-FA nanocomplexes (DOX/MWCNT NCs) exhibited pH-responsive release in acidic environments. Importantly, the DOX/MWCNT NCs targeted tumor cells overexpressing FA receptors (FARs) and effectively inhibited their growth. In vivo anticancer experiments demonstrated that DOX/MWCNT NCs not only enhanced the suppression of tumor growth but also decreased the side effects of free DOX. The developed FA-modified MWCNTs with an unconventionally high DOX loading boosted in vivo anti-tumor efficacy, and the lower systemic toxicity may be utilized for tumor therapy upon clinical translation. [ABSTRACT FROM AUTHOR]

Current guidelines recommend patients with active and mild-to-moderate ulcerative colitis (UC), who have received initial therapy with 5-aminosalicylic acid (5-ASA). In this study, a novel drug delivery vehicle achieved by pH-sensitive hydrogels was applied to 5-ASA. In our previous work, a novel P(CE-MAA-MEG) pH-sensitive hydrogel was successfully synthesized by the heat-initiated free radical polymerization method. The aim of this study is to investigate its site-specific delivering of drugs to the colon and evaluate its colon-targeting characteristicin vivo. 5-ASA was chosen as a model drug and successfully loaded in the hydrogel.In vitroinvestigations were carried out to evaluate its release process. Above all, animal treatment results reveal an obvious effect on the UC healing. Therefore, all results suggested that the developed 5-ASA-P(CE-MAA-MEG) hydrogel (5-ASA-GEL) as a colon-targeting vector might have a great potential application in the UC therapy. [ABSTRACT FROM PUBLISHER]

Hepatocarcinoma animal models, such as the induced tumor model, transplanted tumor model, gene animal model, are significant experimental tools for the evaluation of targeting drug delivery system as well as the pre-clinical studies of liver cancer. The application of antitumor drug-targeting models not only furnishes similar biological characteristics to human liver cancer but also offers guarantee of pharmacokinetic indicators of the liver-targeting preparations. In this article, we have reviewed some kinds of antitumor drug-targeting models of hepatoma and speculated that the research on this field would be capable of attaining a deeper level and expecting a superior achievement in the future. [ABSTRACT FROM PUBLISHER]

Context: Dexamethasone is the major drug in the treatment of ulcerative colitis (UC). However, the extensive or long-time use of dexamethasone causes many toxic side-effects. Ion exchange resins react with external-ions through their own functional groups and Eudragit S occurs degradation when pH > 7. These features make them suitable for oral delivery system. Objective: Resin microcapsule (DRM) composed by 717 anion exchange resin and Eudragit S100 was used to target dexamethasone to the colon to improve its treatment effect on UC and reduce its toxic side-effects. Results: Dexamethasone sodium phosphate (DXSP) was sequentially encapsulated in 717 anion-exchange resin and Eudragit S100 to prepare the DXSP-loaded resin microcapsule (DXSP-DRM). Thein vitrorelease study andin vivostudy of pharmacokinetics and the intestinal drug residues in rat demonstrated the good colon-targeting of DXSP-DRM. Moreover, the DXSP-DRM can reduce the toxic side-effects induced by DXSP and have good therapeutic effects on colitis mouse induced by 2,4,6-trinitrobenzenesulfonic acid. Discussion: Dexamethasone can be targeted to the colon by DRM, thereby enhancing its treatment effect and reducing its toxic side effects. Conclusion: The resin microcapsule system has good colon-targeting and can be used in the development of colon-targeted preparations. [ABSTRACT FROM PUBLISHER]

Context: As a glucocorticoid drug, dexamethasone has good therapeutic effects for ulcerative colitis. pH-sensitive hydrogels could make conventional changes of volume in response with different pH values. Meanwhile, they could load drugs depending on its internal three-dimensional network structure. Objective: Appropriate methods were used to improve the drug-loading capacity of hydrogel and exploring the colon-targeting character of dexamethasone hydrogel. Materials and methods: Different solvents (ethanol and 1,2-propanediol) were employed to dissolve dexamethasone as well as hydrogel monomer materials (poly(ethylene glycol) methyl ether (MPEG)–poly(lactide acid)–acryloyl chloride macromonomer, itaconic acid (IA) and MPEG–methacrylate), then mixing them together to prepare hydrogel through the heat-initiated free radical polymerization method. Differential scanning calorimetry and X-ray diffraction methods were used to verify whether dexamethasone was loaded into hydrogels.In vitrodrug release behavior andin vivopharmacokinetic study were also investigated in detail. Results: Dexamethasone was successfully loaded into hydrogel, and its loading capacity was improved (5 mg/g). Both thein vitrorelease study and thein vivopharmacokinetic study showed the good colon-targeting character of the pH-sensitive P(LE–IA–MEG) hydrogel (Tmax = 1.0 h, Cmax = 2.16 µg/ml of dexamethasone; Tmax = 3.9 h, Cmax = 0.43 µg/ml of dexamethasone hydrogel). Discussion: Dexamethasone could be targeted to the colon site by P(LE–IA–MEG) hydrogel, thereby improving its therapeutic effect and reduce its side effects. Conclusion: P(LE–IA–MEG) hydrogel might have great potential application in colon-targeted drug delivery systems. [ABSTRACT FROM AUTHOR]

Targeting drug system (TDS) or targeted drug delivery system (TDDS) is a new kind of drug delivery system which could make drug to be directly concentrated on the target site with high curative effects and low side-effects. As the quintessence of Chinese culture, traditional Chinese medicine (TCM) has a large advantage in many disease clinical treatments, especially in cancer, hypertension and many other intractable diseases owing to their low toxicity and side-effects relative to western medicine. This article reviews literatures on development of TCM-targeted preparations which were published in the past 10 years. TDS including active-targeting, passive-targeting and physical-chemical-targeting preparations were introduced through domestic and overseas literatures to reveal the unique advantages of TCM-targeting preparations in drug delivery system. In this article, we have reviewed some kinds of TCM-targeting preparations and indicated that great attention should be paid to the research on the TCM-targeting preparations. [ABSTRACT FROM AUTHOR]