Novel Lipid Hybrid Albumin Nanoparticle Greatly Lowered Toxicity of Pirarubicin

Abstract

Pirarubicin (THP) is an effective anthracycline for the treatment of solid tumor. However, its potential side effects are prominent and clinical use is restricted. We aimed to develop a novel pirarubicin-oleic acid complex albumin nanoparticle (THP-OA-AN) in order to reduce the toxicity of THP. Oleic acid, human serum albumin (HSA), and egg yolk lecithin E80 was used to prepare THP-OA-AN. Prepared THP-OA-AN was characterized and animal experiments were conducted to assess its tumor suppression effect, distribution, and toxicity. Comparison between THP and THP-OA-AN showed that, with retained antitumor efficiency, the toxicity of THP-OA-AN is significantly reduced regarding bone marrow suppression, cardiotoxicity, renal toxicity, and gastrointestinal toxicity. This study developed a safe and effective formulation of THP, which has greater potential for clinic use in the tumor therapy.

Co-delivery of Pirarubicin and Paclitaxel by Human Serum Albumin Nanoparticles to Enhance Antitumor Effect and Reduce Systemic Toxicity in Breast Cancers

“…In the current study, Co-AN was prepared as previously described. 38 The nanoparticles showed a uniform size distribution with near spherical morphology (Table 1 and Figure 1A). We investigated whether the drug loading capacity of the HSA nanoparticles was affected by loading multiple therapeutics, and comparable encapsulation efficiency and drug loading capacity were obtained for Co-AN compared to those of THP-AN or PTX-AN (Table 1).…”

ATB0,+ transporter-mediated targeting delivery to human lung cancer cells via aspartate-modified docetaxel-loading stealth liposomes

“…19 All animal experiments were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publications no. The vascular irritation potential of the treatments was evaluated in the marginal ear veins of rabbits according to a previous method.…”

Long-circulating lipoprotein-mimic nanoparticles for smart intravenous delivery of a practically-insoluble antineoplastic drug: Development, preliminary safety evaluations and preclinical pharmacokinetic studies

“…It could be inferred that their uptake by the mononuclear phagocytic system and the subsequent sequestration in liver and spleen should be reduced (Wacker, 2013). The incorporation of albumin would augment these effects by minimizing the possible association of LP6 NPs with serum proteins and/or the rapid clearance of the reticuloendothelial system (Xu et al, 2010;Zhou et al, 2013). In this conceptual framework, the 560 reduced hepatic uptake might have enabled CHL to achieve higher levels in the blood for a prolonged period; compared to CHL solution (Wei et al, 2012).…”

“…Recent reports elucidated that the hydrophobic interactions of albumin with lipophilic drugs and/or fatty acid chains of phospholipids could provide potential stabilization of many 85 drug-loaded phospholipid-enriched NPs (Xu et al, 2010;Zhou et al, 2013;McMahon et al, 2015;Gao et al, 2013). The reactivity of albumin with many targeting legends, via the amino and/or carboxylic groups, can minimize the possible association with serum proteins and/or rapid clearance of the reticuloendothelial system (Xu et al, 2010;Zhou et al, 2013).…”

“…The reactivity of albumin with many targeting legends, via the amino and/or carboxylic groups, can minimize the possible association with serum proteins and/or rapid clearance of the reticuloendothelial system (Xu et al, 2010;Zhou et al, 2013).…”