Reduction-Responsive and Multidrug Deliverable Albumin Nanoparticles: An Antitumor Drug to Abraxane against Human Pancreatic Tumor-Bearing Mice

Abstract

Many macromolecular antitumor drugs were developed based on the enhanced permeability and retention (EPR) effect, for example, albumin-bound paclitaxel nanoparticles (nab-PTX and Abraxane) and pegylated liposomal doxorubicin (Doxil). However, these EPR effect-based therapeutic systems are less effective in malignant tumors with low vascular permeability, such as pancreatic tumors. Because the EPR effect depends on nanoparticles’ size, we first determined nanoparticles’ size associated with a high tumor-targeting rate in a human pancreatic tumor xenograft model with low vascular permeability. Abraxane appears to behave as an albumin monomer (7 nm) in the blood circulation following intravenous injection. The in vitro and in vivo tumor-targeted delivery and antitumor activity of PTX-loaded albumin nanoparticles were significantly improved by optimizing the mean nanoparticle diameter to 30 nm. Furthermore, nitric oxide was added to 30 nm PTX-loaded albumin nanoparticles to examine the feasibility of albumin nanoparticles as a platform for multiple drug delivery. Their antitumor effect was evaluated in an orthotopic transplantation mouse model of a human pancreatic tumor. The nitric oxide PTX-loaded 30 nm albumin nanoparticle treatment on model mice achieved a significantly higher survival rate than Abraxane treatment. These findings suggest that 30 nm albumin nanoparticles have a high therapeutic effect as a useful platform for multiple drugs against human pancreatic tumors.

Drug Delivery Strategies for the Treatment of Pancreatic Cancer

“…They are biocompatible, biodegradable, and well-tolerated with a high safety profile. Albumin nanocarriers have been reported to improve the stability of various therapeutic payloads, enhance drug uptake and subsequent accumulation within tumors, and facilitate prolonged circulation time [ 137 , 152 , 153 , 154 , 155 , 156 ]. On the other hand, because albumin is an endogenous protein, there may be batch-to-batch variations in size and purity of albumin-based products, which may affect commercial scalability.…”

“…Abraxane ® was the first albumin-based nanoparticle to be approved in 2013 [ 156 , 161 ]. Abraxane ® , also known as nab-paclitaxel (nanoparticle albumin-bound paclitaxel), is an albumin-stabilized paclitaxel authorized for first-line treatment of metastatic pancreatic cancer in combination with gemcitabine.…”

Polymer-Based Nanosystems—A Versatile Delivery Approach

“…Albumin represents an appealing protein-based macromolecular carrier due to its non-toxicity, non-immunogenicity, biocompatibility, easy incorporation of various drugs, and ability to bind with proteins [21,82,83]. Albumin nanoparticles have been shown to exhibit enhanced affinity for anti-cancer drugs, including paclitaxel [84][85][86][87] (FDAapproved nanoformulation as Abraxane ® /ABI-007 (Celgene) [88]), doxorubicin [87,[89][90][91][92], docetaxel [93][94][95][96], tacrolimus [87,97], and curcumin [98,99].…”

Peptide Modified Albumin–Paclitaxel Nanoparticles for Improving Chemotherapy and Preventing Metastasis

“…In order to overcome these shortcomings, many new drug delivery systems have been developed, such as liposomes, polymers, carbon nanotubes, micelles, proteins, and so on. [1][2][3][4][5] Taking paclitaxel as an example, several formulations were used in clinic, including Taxol, Lipusu, and Abraxane. Abraxane uses human serum albumin (HSA) as a carrier, compared with Taxol and Lipusu, it can be directly administered without the pretreatment of corticosteroids and antihistamines before intravenous injection, and the administration time is also significantly shortened from >3 h to 30 min.…”