Preparation and <i>in Vitro</i> Analysis of Human Serum Albumin Nanoparticles Loaded with Anthracycline Derivatives

Abstract

Nanoparticles prepared using human serum albumin (HSA) have emerged as versatile carriers for improving the pharmacokinetic profile of drugs. The desolvation of HSA using ethanol followed by stabilization through crosslinking with glutaraldehyde is a common technique for preparing HSA nanoparticles, but our knowledge concerning the characteristics (or functions) of HSA nanoparticles and their efficiency when loaded with drugs is limited. To address this issue in more detail, we prepared anthracycline-loaded HSA nanoparticles. Doxorubicin-loaded HSA nanoparticles with a size similar to doxorubicin-unloaded particles could be prepared by desolvating at a higher pH (8-9), and the size (100-150 nm) was optimum for delivery to tumor tissues. Using this procedure, HSA nanoparticles were loaded with other anthracycline derivatives, and all showed cytotoxicity in cancer cells. However, the efficiency of drug loading and dissolution rate were different among them possibly due to the differences in the type of association of the drugs on nanoparticles (doxorubicin and daunorubicin; covalently bound to nanoparticles, pirarubicin; both covalently bound to and adsorbed on nanoparticles, aclarubicin; adsorbed on nanoparticles). Since the formulation of such drug-loaded HSA nanoparticles should be modified for efficient delivery to tumors, the findings reported herein provide the useful information for optimizing the formulation and the production process for the HSA nanoparticles using a desolvation technique.

Development of Meloxicam-Human Serum Albumin Nanoparticles for Nose-to-Brain Delivery via Application of a Quality by Design Approach

“…Particle size <100 nm raises nanotoxicity issues. Human serum albumin (HSA) nanoparticles with a size below 200 nm have an enhanced permeation and retention (EPR) effect [37]. It is linked to the quality, safety, and efficacy profile of the preparation.…”

“…Equilibrium dialysis (ED) is the most commonly used method and is frequently considered the gold standard [45]. An RED device was developed in order to reduce the time to equilibrium, and therefore providing results faster than using other methods [37]. RED improves the accuracy of measurements and minimizes inaccuracy due to volumetric deviations in measurements.…”

When Albumin Meets Liposomes: A Feasible Drug Carrier for Biomedical Applications

“…These preparations take advantage of the following inherent structural and physiological characteristics of albumin-Albumin has a good biocompatibility with a long plasma half-life, the aqueous solubility of endogenous and exogenous hydrophobic substances can be improved by their binding to albumin, and the cysteine residue at position 34 of albumin readily reacts with oxidative products and other thiol groups (Figure 1). Both academia and industry have used various approaches to develop novel albuminassociated pharmaceutical preparations: (i) albumin-drug conjugation to prolong blood retention [11][12][13][14][15], (ii) nanoparticulation by albumin aggregates to improve stability and the loading efficiency of hydrophobic substances [16][17][18], (iii) liposome, micelles, niosomes, and emulsions fused with albumin to compensate for their drawbacks [19][20][21][22][23]. Among these approaches, adapting albumin for use in a liposome-based drug delivery system (DDS) has shown promising results.…”

Pharmaceutical Technology Innovation Strategy Based on the Function of Blood Transport Proteins as DDS Carriers for the Treatment of Intractable Disorders and Cancer

“…The desolvation technique is a rapid and straightforward method to prepare protein nanoparticles. Although several researchers have prepared and evaluated the anticancer activity of anticancer agent-loaded albumin nanoparticles in vitro and in vivo, 55,56) the optimal conditions for the preparation of anticancer agent-loaded albumin nanoparticles remain unclear. Using doxorubicin as a model anticancer drug, we established the optimal conditions for preparing doxorubicin-loaded albumin nanoparticles for delivery to solid tumor sites via the EPR effect: desolvating agent, ethanol; albumin concentration, 20 mg/mL; pH, 8.5; and doxorubicin concentration, 0.5 mg/mL (Fig.…”