Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8505, Japan.
Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, Tokushima 770-8505, Japan; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
J Control Release. 2015 Dec 28;220(Pt A):406-413. doi: 10.1016/j.jconrel.2015.11.002. Epub 2015 Nov 6.
Liposomes have proven to be a viable means for the delivery of chemotherapeutic agents to solid tumors. However, significant variability has been detected in their intra-tumor accumulation and distribution, resulting in compromised therapeutic outcomes. We recently examined the intra-tumor accumulation and distribution of weekly sequentially administered oxaliplatin (l-OHP)-containing PEGylated liposomes. In that study, the first and second doses of l-OHP-containing PEGylated liposomes were distributed diversely and broadly within tumor tissues, resulting in a potent anti-tumor efficacy. However, little is known about the mechanism underlying such a diverse and broad liposome distribution. Therefore, in the present study, we investigated the influence of dosage interval on the intra-tumor accumulation and distribution of "empty" PEGylated liposomes. Intra-tumor distribution of sequentially administered "empty" PEGylated liposomes was altered in a dosing interval-dependent manner. In addition, the intra-tumor distribution pattern was closely related to the chronological alteration of tumor blood flow as well as vascular permeability in the growing tumor tissue. These results suggest that the sequential administrations of PEGylated liposomes in well-spaced intervals might allow the distribution to different areas and enhance the total bulk accumulation within tumor tissue, resulting in better therapeutic efficacy of the encapsulated payload. This study may provide useful information for a better design of therapeutic regimens involving multiple administrations of nanocarrier drug delivery systems.
脂质体已被证明是向实体瘤递送化疗药物的一种可行手段。然而，在其肿瘤内积累和分布方面存在显著的可变性，导致治疗效果受损。我们最近研究了每周连续给予含奥沙利铂（l-OHP）的聚乙二醇化脂质体的肿瘤内积累和分布。在该研究中，第一和第二剂量的含 l-OHP 的聚乙二醇化脂质体在肿瘤组织内广泛而多样化地分布，从而产生强大的抗肿瘤疗效。然而，对于这种多样化和广泛的脂质体分布的机制知之甚少。因此，在本研究中，我们研究了剂量间隔对“空”聚乙二醇化脂质体在肿瘤内积累和分布的影响。顺序给予的“空”聚乙二醇化脂质体在肿瘤内的分布随剂量间隔而变化。此外，肿瘤内的分布模式与生长肿瘤组织中肿瘤血流的时间变化以及血管通透性密切相关。这些结果表明，在间隔良好的时间间隔内连续给予聚乙二醇化脂质体可能允许分布到不同区域，并增强肿瘤组织内的总总体积累，从而提高包裹有效载荷的治疗效果。这项研究可能为涉及多次给予纳米载体药物递送系统的治疗方案的更好设计提供有用信息。
