Parthasarathy R, Gilbert B, Mehta K
Department of Endocrinology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Cancer Chemother Pharmacol. 1999;43(4):277-83. doi: 10.1007/s002800050895.
To optimize the delivery of all-trans-retinoic acid (ATRA) to lung tissue, we determined the potential of vehiculating the drug in liposomes (L-ATRA) and delivering it via aerosol. Liposomes may provide a means to prevent local irritation of lung tissue and reduce pulmonary toxicity, prolong therapeutic levels and generate high drug concentrations at the tumor sites. Cumulatively, this would result in reduced systemic toxicity and enhanced drug efficacy.
Previous studies have shown that liposomes can serve as excellent carriers for otherwise poorly soluble ATRA. Delivery of ATRA to the lung tissue of mice was accomplished by nebulization of L-ATRA. The liposomes in the aerosol were relatively uniform (309 +/- 138 nm), stable, and retained the drug well.
The drug was effectively delivered at high concentrations (10 +/- 2 microg/g of tissue) to the lungs of mice and was retained for at least up to 96 h after a single exposure to L-ATRA aerosol. No appreciable levels of ATRA were detected in the blood or the liver of treated mice. The aerosol-delivered ATRA was biologically active as demonstrated by its ability to induce the expression of tissue-type transglutaminase.
Aerosol delivery of L-ATRA offers an effective way to deliver high levels of ATRA to the lung without apparent pulmonary toxic effects.
为了优化全反式维甲酸（ATRA）向肺组织的递送，我们确定了将该药物包裹于脂质体中（L-ATRA）并通过气雾剂递送的潜力。脂质体可能提供一种防止肺组织局部刺激和降低肺部毒性的方法，延长治疗水平并在肿瘤部位产生高药物浓度。总的来说，这将导致全身毒性降低和药物疗效增强。
先前的研究表明，脂质体可作为原本难溶性ATRA的优良载体。通过雾化L-ATRA将ATRA递送至小鼠肺组织。气雾剂中的脂质体相对均匀（309±138nm）、稳定且能很好地保留药物。
单次暴露于L-ATRA气雾剂后，药物以高浓度（10±2μg/g组织）有效递送至小鼠肺部，并至少保留96小时。在治疗小鼠的血液或肝脏中未检测到明显水平的ATRA。雾化递送的ATRA具有生物活性，这通过其诱导组织型转谷氨酰胺酶表达的能力得以证明。
雾化递送L-ATRA提供了一种将高水平ATRA递送至肺部而无明显肺部毒性作用的有效方法。
