Effects of Particle Hydrophobicity, Surface Charge, Media pH Value and Complexation with Human Serum Albumin on Drug Release Behavior of Mitoxantrone-Loaded Pullulan Nanoparticles

Abstract

We prepared two types of cholesterol hydrophobically modified pullulan nanoparticles (CHP) and carboxyethyl hydrophobically modified pullulan nanoparticles (CHCP) substituted with various degrees of cholesterol, including 3.11, 6.03, 6.91 and 3.46 per polymer, and named CHP−3.11, CHP−6.03, CHP−6.91 and CHCP−3.46. Dynamic laser light scattering (DLS) showed that the pullulan nanoparticles were 80–120 nm depending on the degree of cholesterol substitution. The mean size of CHCP nanoparticles was about 160 nm, with zeta potential −19.9 mV, larger than CHP because of the carboxyethyl group. A greater degree of cholesterol substitution conferred greater nanoparticle hydrophobicity. Drug-loading efficiency depended on nanoparticle hydrophobicity, that is, nanoparticles with the greatest degree of cholesterol substitution (6.91) showed the most drug encapsulation efficiency (90.2%). The amount of drug loading increased and that of drug release decreased with enhanced nanoparticle hydrophobicity. Nanoparticle surface-negative charge disturbed the amount of drug loading and drug release, for an opposite effect relative to nanoparticle hydrophobicity. The drug release in pullulan nanoparticles was higher pH 4.0 than pH 6.8 media. However, the changed drug release amount was not larger for negative-surface nanoparticles than CHP nanoparticles in the acid release media. Drug release of pullulan nanoparticles was further slowed with human serum albumin complexation and was little affected by nanoparticle hydrophobicity and surface negative charge.

Soft Interaction in Liposome Nanocarriers for Therapeutic Drug Delivery

“…As the amphiphilic self-assembly is a dynamic process, the micellar aggregates present a dynamic structure in which the unimers are rapidly exchanged between micelles and the bulk solution (with lifetimes between 10 −5 and 10 −3 s) [6]. The shape and size of a given nanocarrier aggregate depends on the molecular geometry of its component surfactant molecules and the solution conditions, such as surfactant concentration, temperature, pH, and ionic strength [6,14]. Control over the shapes allows the possibility to develop and manipulate nanostructure architectures.…”

“…As schematically reported in Figure 1, with the increment of the C pp value the structure of aggregates can range from spherical micelles ( C pp ≤ 1/3), to cylindrical micelles (1/3 ≤ C pp ≤ 1/2), vesicles (1/2 ≤ C pp ≤ 1), and lamellar structures ( C pp = 1) [6]. For larger values of the critical packing parameter C pp the amphiphiles will assemble into “inverted” phases [6,14]. …”

“…The delivery mechanism and liposome efficiency in drug delivery processes are strongly influenced by the typology and density of the charge of the liposome surface through its ζ-potential [14,22]. A high electrostatic repulsion on the surface of charged liposomes prevents their aggregation and flocculation and could promote their interaction with cells [7,8,9,10,11,22].…”

“…Those features play a crucial role [8,14] as they influence both their biodistribution and passive targeting abilities upon drug administration. For these reasons, liposome size, colloidal stability, and aggregation properties (as well as their time evolution) should be probed (in situ) in solution conditions that reproduce standard administration conditions.…”

Cholesterol-Modified Amino-Pullulan Nanoparticles as a Drug Carrier: Comparative Study of Cholesterol-Modified Carboxyethyl Pullulan and Pullulan Nanoparticles

“…The tumor-targeting function of CHP NPs results from the size, about 100 nm, and the high drug-loading amount of CHP NPs depends on the cholesterol substitution degree in polymer [31,32]. Only with an appropriate range of cholesterol substitution can polymer assemble into a core-shell structured NP [29]; within this range, the greater the substitution degree, the higher the drug-loading amount [32].…”