Polymeric micelles for potentiated antiulcer and anticancer activities of naringin

• Published in: International journal of nanomedicine Vol. 13; pp. 1009 - 1027
• Main Authors: Mohamed, Elham Abdelmonem, Abu Hashim, Irhan Ibrahim, Yusif, Rehab Mohammad, Shaaban, Ahmed Abdel Aziz, El-Sheakh, Ahmed Ramadan, Hamed, Mohammed Fawzy, Badria, Farid Abd Elreheem
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2018; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Animals; Anti-Ulcer Agents - administration & dosage; Anti-Ulcer Agents - chemistry; Anti-Ulcer Agents - pharmacology; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antioxidants; antitumor activity; antiulcer; Antiulcer agents; Apoptosis; Ascites; B cells; Bioavailability; Biological Availability; Cancer; Cancer therapies; Cancer treatment; Carcinoma; Cell Line, Tumor; Citrus; Citrus fruits; Colorectal cancer; Cytotoxicity; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Drug delivery systems; Drug dosages; Drug Liberation; Drug resistance; Ethanol; Female; Flavanones - administration & dosage; Flavanones - chemistry; Flavanones - pharmacology; Humans; in vitro cytotoxicity; Interleukins; Liver cancer; Male; Mice; Micelles; Nanoparticles; naringin; Necrosis; Original Research; Particle Size; Permeability; Pharmaceutical sciences; Pharmacy; pluronic F68; Poloxamer - chemistry; polymeric micelles; Rats, Sprague-Dawley; Solubility; Superoxides; Surfactants; Tumor necrosis factor-TNF; Tumors; Ulcer - chemically induced; Ulcer - drug therapy; Ulcers; Egypt; in vitro cytotoxicity; naringin; polymeric micelles; antitumor activity; antiulcer; pluronic F68
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S154325

Naringin is one of the most interesting phytopharmaceuticals that has been widely investigated for various biological actions. Yet, its low water solubility, limited permeability, and suboptimal bioavailability limited its use. Therefore, in this study, polymeric micelles of naringin based on pluronic F68 (PF68) were developed, fully characterized, and optimized. The optimized formula was investigated regarding in vitro release, storage stability, and in vitro cytotoxicity vs different cell lines. Also, cytoprotection against ethanol-induced ulcer in rats and antitumor activity against Ehrlich ascites carcinoma in mice were investigated. Nanoscopic and nearly spherical 1:50 micelles with the mean diameter of 74.80±6.56 nm and narrow size distribution were obtained. These micelles showed the highest entrapment efficiency (EE%; 96.14±2.29). The micelles exhibited prolonged release up to 48 vs 10 h for free naringin. The stability of micelles was confirmed by insignificant changes in drug entrapment, particle size, and retention (%) (91.99±3.24). At lower dose than free naringin, effective cytoprotection of 1:50 micelles against ethanol-induced ulcer in rat model has been indicated by significant reduction in mucosal damage, gastric level of malondialdehyde, gastric expression of tumor necrosis factor-alpha, caspase-3, nuclear factor kappa-light-chain-enhancer of activated B cells, and interleukin-6 with the elevation of gastric reduced glutathione and superoxide dismutase when compared with the positive control group. As well, these micelles provoked pronounced antitumor activity assessed by potentiated in vitro cytotoxicity particularly against colorectal carcinoma cells and tumor growth inhibition when compared with free naringin. In conclusion, 1:50 naringin-PF68 micelles can be represented as a potential stable nanodrug delivery system with prolonged release and enhanced antiulcer as well as antitumor activities.