Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
Department of Natural Products and Alternative Medicine, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
Int J Biol Macromol. 2019 May 1;128:825-838. doi: 10.1016/j.ijbiomac.2019.01.142. Epub 2019 Jan 26.
Daunorubicin hydrochloride (DAUN·HCl), due to low oral bioavailability poses the hindrance to be marketed as an oral formulation.
To develop a natural biodegradable macromolecule i.e. Chitosan (CS)-coated-DAUN-PLGA-poly(lactic-co-glycolic acid)-Nanoparticles (NPs) with an aim to improve oral-DAUN bioavailability and to develop as well as validate UHPLC-MS/MS (ESI/Q-TOF) method for plasma quantification and pharmacokinetic analysis (PK) of DAUN.
A particle size (198.3 ± 9.21 nm), drug content (47.06 ± 1.16 mg/mg) and zeta potential (11.3 ± 0.98 mV), consisting of smooth and spherical shape was observed for developed formulation. Cytotoxicity studies for CS-DAUN-PLGA-NPs revealed; a comparative superiority over free DAUN-S (i.v.) in human breast adenocarcinoma cell lines (MCF-7) and a higher permeability i.e. 3.89 folds across rat ileum, as compared to DAUN-PLGA-NPs (p < 0.01) inhuman colon adenocarcinoma cell line (Caco-2). For PK, CS-DAUN-PLGA-NPs as compared to DAUN-S, exhibited a 10.0 fold higher bioavailability in Wister rat's plasma due to presence of a natural biodegradable macromolecule i.e. CS coated on the PLGA-NPs. With regard to bioanalytical method, easy as well as a rapid method for DAUN-plasma quantification was developed as; 2.75 min and 528.49/321.54 m/z for DAUN along with 1.94 min and 544.36/397.41 m/z for IS i.e. Doxorubicin, for elution time and transition, respectively.
A novel natural biodegradable approach used in the preparation of CS coated DAUN-NPs for oral administration of DAUN is reported in this study which is can be utilized as an alternate for intravenous therapy.
盐酸柔红霉素（DAUN·HCl）由于口服生物利用度低，因此难以作为口服制剂上市。
开发一种天然可生物降解的大分子，即壳聚糖（CS）包覆的 DAUN-PLGA-聚（乳酸-共-乙醇酸）-纳米粒（NPs），旨在提高口服 DAUN 的生物利用度，并开发和验证 UHPLC-MS/MS（ESI/Q-TOF）方法用于血浆定量和 DAUN 的药代动力学分析（PK）。
所开发的制剂具有 198.3±9.21nm 的粒径、47.06±1.16mg/mg 的药物含量和 11.3±0.98mV 的 zeta 电位，呈光滑球形。CS-DAUN-PLGA-NPs 的细胞毒性研究表明，与静脉注射的游离 DAUN-S（i.v.）相比，在人乳腺癌腺癌细胞系（MCF-7）中具有比较优势，并且在大鼠回肠中的通透性更高，即与人结肠腺癌细胞系（Caco-2）中的 DAUN-PLGA-NPs 相比提高了 3.89 倍（p<0.01）。在 PK 方面，CS-DAUN-PLGA-NPs 与 DAUN-S 相比，在 Wister 大鼠血浆中的生物利用度提高了 10.0 倍，这是由于存在天然可生物降解的大分子即 CS 包覆在 PLGA-NPs 上。关于生物分析方法，开发了一种简单快速的 DAUN-血浆定量方法，即 DAUN 的洗脱时间和转换分别为 2.75min 和 528.49/321.54m/z，IS 即阿霉素为 1.94min 和 544.36/397.41m/z。
本研究报道了一种新型的天然可生物降解方法，用于制备口服给药的 CS 包覆的 DAUN-NPs，可作为静脉治疗的替代方法。
