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Stability of freeze-dried pH-responsive dextrin nanogels containing doxorubicin

Asian Journal of Pharmaceutical Sciences 2016年第5期11卷 648-654页

作者： somkamol manchun Crispin R.Dass Pornsak Sriamornsak Department of Pharmaceutical Technology Faculty of PharmacySilpakorn UniversityNakhon Pathom 73000Thailand Pharmaceutical Biopolymer Group(PBiG) Faculty of PharmacySilpakorn UniversityNakhon Pathom 73000Thailand School of Pharmacy Faculty of Health SciencesCurtin UniversityPerth 6845Australia Curtin Health Innovation Research Institute of Ageing and Chronic Disease Bentley 6102Australia

Induction of non-specific toxicities by doxorubicin(DOX) has restricted conventional DOXbased chemotherapy. p H-responsive dextrin nanogels(DNGs) have been fabricated in order to incorporate and deliver DOX to specific(targeted) sites. However, adequate stability studies of DOX-loaded DNGs are required for selection of storage conditions. The aim of this study was therefore to evaluate the accelerated(25 °C/60% RH) and long-term(5 °C) stability of DNGs prepared with formaldehyde(FDNGs) and glyoxal(GDNGs) as cross-linker by determining the change in their physicochemical properties. The mean diameter decreased with time during long-term storage. The drug content between freshly prepared(initial day) and after storage at 5 °C for 180 days of DOX-loaded FDNGs and DOX-loaded GDNGs was not significantly different(p > 0.05), but decreased after storage under the accelerated condition. The release of DOX from all DNGs was pH-dependent. However, DNGs kept under the accelerated condition showed higher amount of DOX release than those stored at 5 °C and the freshly prepared ones. The results indicate that the stability of DNGs could be improved by their storage at 5 °C.

关键词： Stability Nanogels Dextrin

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Characterization and in vitro release studies of oral microbeads containing thiolated pectin–doxorubicin conjugates for colorectal cancer treatment

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Asian Journal of Pharmaceutical Sciences 2017年第6期12卷 509-520页

作者： Kamonrak Cheewatanakornkool Sathit Niratisai somkamol manchun Crispin R.Dass Pornsak Sriamornsak Department of Pharmaceutical Technology Faculty of PharmacySilpakorn UniversityNakhon Pathom 73000Thailand Pharmaceutical Biopolymer Group(PBiG) Faculty of PharmacySilpakorn UniversityNakhon Pathom 73000Thailand Department of Pharmaceutical Chemistry Faculty of PharmacySilpakorn UniversityNakhon Pathom 73000Thailand Thailand Institute of Scientific and Technological Research Klong LuangPathum Thani 12120Thailand School of Pharmacy Faculty of Health SciencesCurtin UniversityPerthWA 6845Australia Curtin Health Institute for Research Innovation Curtin UniversityPerthWA 6845Australia

Novel oral microbeads were developed based on a biopolymer–drug conjugate of doxorubicin(DOX) conjugated with thiolated pectin via reducible disulfide bonds. The microbeads were fabricated by ionotropic gelation with cations such as Al3+, Ca2+ and Zn2+. The results showed that using zinc acetate can produce the strongest microbeads with spherical ***, the microbeads prepared from thiolated pectin–DOX conjugate were very soft and irregular in shape. To produce more spherical microbeads with suitable strength, the native pectin was then added to the formulations. The particle size of the microbeads ranged from 0.87 to 1.14 mm. The morphology of the microbeads was characterized by optical and scanning electron microscopy. DOX was still in crystalline form when used in preparing the microbeads, as confirmed by powder X-ray diffractometry. Drug release profiles showed that the microbeads containing thiolated pectin–DOX conjugate exhibited reduction-responsive character;in reducing environments, the thiolated pectin–DOX conjugate could uncouple resulting from a cleavage of the disulfide linkers and consequently release the DOX. The best-fit release kinetics of the microbeads containing thiolated pectin–DOX conjugate, in the medium without reducing agent, fit the Korsmeyer–Peppas model while those in the medium with reducing agent fit a zero-order release model. These results suggested that the microbeads containing thiolated pectin–DOX conjugate may be a promising platform for cancer-targeted delivery of DOX, exploiting the reducing environment typically found in tumors.

关键词： Microbeads Thiolated pectin Doxorubicin Conjugate Colorectal cancer

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