کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5521612 1545310 2017 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research paperNanosized complexation assemblies housed inside reverse micelles churn out monocytic delivery cores for bendamustine hydrochloride
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
پیش نمایش صفحه اول مقاله
Research paperNanosized complexation assemblies housed inside reverse micelles churn out monocytic delivery cores for bendamustine hydrochloride
چکیده انگلیسی

ObjectiveWe explore a plausible method of targeting bendamustine hydrochloride (BM) to circulatory monocytes by exploiting their intrinsic endocytic/phagocytic capability.MethodsWe do so by complexation of sodium alginate and chitosan inside dioctyl sulfo succinate sodium (AOT) reverse micelles to form bendamustine hydrochloride loaded nanoparticles (CANPs). Dynamic light scattering, electrophoretic mobility and UV spectroscopy were used to detail intra-micellar complexation dynamics and to prove that drug was co-captured during interaction of carbohydrate polymers. A fluorescent conjugate of drug (RBM) was used to trace its intracellular fate after its loading into nanoparticles.ResultsCANPs were sized below 150 nm, had 75% drug entrapment and negative zeta potential (−30 mV). Confocal microscopy demonstrated that developed chitosan alginate nanoparticles had the unique capability to carry BM specifically to its site of action. Quantitative and mechanism based cell uptake studies revealed that monocytes had voracious capacity to internalize CANPs via simultaneous scavenger receptor based endocytic and phagocytic mechanism. Comparative in vitro pharmacokinetic studies revealed obtainment of significantly greater intracellular drug levels when cells were treated with CANPs. This caused reduction in IC50 (22.5 ± 2.1 μg/mL), enhancement in G2M cell cycle arrest, greater intracellular reactive oxygen species generation, and increased apopotic potential of bendamustine hydrochloride in THP-1 cells.ConclusionSelective monocytic targeting of bendamustine hydrochloride using carbohydrate constructs can prove advantageous in case of leukemic disorders displaying overabundance of such cells.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutics and Biopharmaceutics - Volume 113, April 2017, Pages 198-210
نویسندگان
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