Ray Sayantan, Saha Suman, Sa Biswanath, Chakraborty Jui
CSIR-Central Glass and Ceramic Research Institute, 196, Raja S.C. Mullick Road, Jadavpur, Kolkata, 700 032, India.
Jadavpur University, Jadavpur, Kolkata, 700 032, India.
Drug Deliv Transl Res. 2017 Apr;7(2):259-275. doi: 10.1007/s13346-016-0351-6.
Considering the existing drawbacks of methotrexate (MTX) with respect to its solubility and toxicity, we incorporated it in a nanoceramic matrix, Mg-Al-layered double hydroxide (LDH) to form LDH-MTX nanoparticles, and the same was in turn encapsulated in a nontoxic and biodegradable polymer, poly (D,L-lactide-co-glycolide) (PLGA), to arrest the initial burst release and dose-dumping-related toxicity, already reported by our group. Our present study was designed to evaluate the pharmacokinetics, tissue distribution, survival rate of the test animals, and antitumor efficacy of the PLGA-LDH-MTX nanoparticles and its counterpart without LDH, PLGA-MTX nanoparticles compared with bare MTX. The median lethal dose (LD) of the former was higher, compared with bare MTX, using Balb/c nude mice, indicating it to be completely safe for use. Also, a comparative pharmacokinetic and antitumour efficacy study using MTX, PLGA-MTX, and PLGA-LDH-MTX nanoparticles in osteosarcoma-induced Balb/c nude mice in vivo demonstrated superiority of PLGA-LDH-MTX as compared to PLGA-MTX and bare MTX. The results suggest that PLGA-LDH-MTX nanoparticles might exhibit potential advantages over the present-day chemotherapy over bare MTX, for the possibility of treatment of osteosarcoma.
考虑到甲氨蝶呤（MTX）在溶解性和毒性方面存在的缺点，我们将其掺入纳米陶瓷基质——镁铝层状双氢氧化物（LDH）中，以形成LDH-MTX纳米颗粒，然后将其封装在无毒且可生物降解的聚合物聚（D，L-丙交酯-共-乙交酯）（PLGA）中，以抑制我们团队之前报道的初始突释和剂量倾泻相关毒性。我们目前的研究旨在评估PLGA-LDH-MTX纳米颗粒及其不含LDH的对应物PLGA-MTX纳米颗粒与单纯MTX相比的药代动力学、组织分布、实验动物存活率和抗肿瘤疗效。使用Balb/c裸鼠时，前者的半数致死剂量（LD）比单纯MTX更高，表明其使用完全安全。此外，在骨肉瘤诱导的Balb/c裸鼠体内使用MTX、PLGA-MTX和PLGA-LDH-MTX纳米颗粒进行的比较药代动力学和抗肿瘤疗效研究表明，PLGA-LDH-MTX比PLGA-MTX和单纯MTX更具优势。结果表明，PLGA-LDH-MTX纳米颗粒在治疗骨肉瘤方面可能比目前的化疗药物单纯MTX具有潜在优势。
