Neupane Yub Raj, Srivastava Manish, Ahmad Nafees, Kumar Neeraj, Bhatnagar Aseem, Kohli Kanchan
Formulation Development Laboratory, Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard University, New Delhi, India.
Formulation Development Laboratory, Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard University, New Delhi, India.
Int J Pharm. 2014 Dec 30;477(1-2):601-12. doi: 10.1016/j.ijpharm.2014.11.001. Epub 2014 Nov 6.
The aim of this study was to design and fabricate nanostructured lipid carrier (NLC) for the potential oral delivery of decitabine (DCB). NLC was prepared by cold homogenization technique and optimized by the Box-Behnken experimental design. It was further characterized by particle size, zeta potential, transmission electron microscopy (TEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), in vitro release study, and stability study. Moreover, ex vivo and in vivo efficacy of the NLC was assessed by gut permeation study, γ scintigraphy imaging, and MTT assay. NLC was found to have particle size (116.64 ± 6.67 nm), zeta potential (-31.8 ± 0.96 mV) and sustained drug release (80.23 ± 4.67%) up to 24h. TEM and AFM proved that the particles were spherical in shape and smooth surface. DSC and XRD studies had demonstrated the reduced crystallinity and stability enhancing effect of the NLC. Stability studies revealed the changes in the observed parameters up to 45 days were not significantly differences (p>0.05). Ex vivo gut permeation study showed 4-folds increment in the permeation of drug compared with the plain drug solution. γ Scintigraphy imaging and MTT assay results inferred that DCB loaded NLC possesses excellent cytotoxic activity against cancer cells. Thus, NLC holds high potential for the oral delivery of DCB to treat cancer cells and future prospects for the industrial purpose.
本研究的目的是设计并制备纳米结构脂质载体（NLC），用于阿扎胞苷（DCB）的潜在口服给药。通过冷均质技术制备NLC，并采用Box-Behnken实验设计进行优化。通过粒径、zeta电位、透射电子显微镜（TEM）、原子力显微镜（AFM）、差示扫描量热法（DSC）、X射线衍射（XRD）、体外释放研究和稳定性研究对其进行进一步表征。此外，通过肠道渗透研究、γ闪烁成像和MTT试验评估了NLC的体外和体内疗效。发现NLC的粒径为（116.64±6.67 nm），zeta电位为（-31.8±0.96 mV），药物持续释放长达24小时，释放率为（80.23±4.67%）。TEM和AFM证明颗粒呈球形且表面光滑。DSC和XRD研究表明NLC的结晶度降低且具有稳定性增强作用。稳定性研究表明，在长达45天的时间内观察到的参数变化无显著差异（p>0.05）。体外肠道渗透研究表明，与普通药物溶液相比，药物的渗透率提高了4倍。γ闪烁成像和MTT试验结果表明，负载DCB的NLC对癌细胞具有优异的细胞毒性活性。因此，NLC在口服递送DCB以治疗癌细胞方面具有很高的潜力，并且在工业应用方面具有广阔的前景。
