Physicochemical characterization of drug nanocarriers

Abstract

Pharmaceutical design has enabled important advances in the prevention, treatment, and diagnosis of diseases. The use of nanotechnology to optimize the delivery of drugs and diagnostic molecules is increasingly receiving attention due to the enhanced efficiency provided by these systems. Understanding the structures of nanocarriers is crucial in elucidating their physical and chemical properties, which greatly influence their behavior in the body at both the molecular and systemic levels. This review was conducted to describe the principles and characteristics of techniques commonly used to elucidate the structures of nanocarriers, with consideration of their size, morphology, surface charge, porosity, crystalline arrangement, and phase. These techniques include X-ray diffraction, small-angle X-ray scattering, dynamic light scattering, zeta potential, polarized light microscopy, transmission electron microscopy, scanning electron microcopy, and porosimetry. Moreover, we describe some of the commonly used nanocarriers (liquid crystals, metal-organic frameworks, silica nanospheres, liposomes, solid lipid nanoparticles, and micelles) and the main aspects of their structures.

Keywords: controlled drug release; drug delivery; nanoparticles; physicochemical properties.

Figure 1

Schematic nanocarrier structures: (A) liposome, (B) micelle, (C) silica nanoparticles, and (D) metal–organic framework.

Figure 2

Schematic mechanism of X-ray incidence into the sample and the classified scattering regimes (WAXS, SAXS, and USAXS), indicating the scattering angle explored by each one (WAXS: >10°; SAXS: between 0.1° and 10°; USAXS: between 0.001° and 0.1°). Abbreviations: SAXS, small-angle X-ray scattering; USAXS, ultra-small-angle X-ray scattering; WAXS, wide-angle X-ray scattering.

Figure 3

Examples of (A and B) anisotropic and (C) isotropic SAXS curves: hexagonal and lamellar phases of liquid crystalline formulations composed of (A) PPG-5 Ceteth 20, isopropyl palmitate, and water, and (B) oleic acid and water;, and (C) shows the curve for a diluted colloidal suspension of ZnO quantum dots. Abbreviation: SAXS, small-angle X-ray scattering.

Figure 4

Schematic illustration of the electrical double layer at the surface of solution-phase nanoparticles, and the graphical response produced by this analysis.

Figure 5

Scanning electron micrograph of a metal–organic framework (MOF) based on cyclodextrin and potassium. Magnified 300×.

Figure 6

Photomicrograph of a hexagonal liquid crystal prepared with Ceteth 10, isopropyl palmitate, and water. Magnified 20×. Journal of Sol-Gel Science and Technology. Manaia EB, Kaminski RCK, Soares CP, Meneau F, Pulcinelli SH, Santilli CV, Chiavacci LA. Liquid crystalline formulations containing modified surface TiO₂ nanoparticles obtained by sol-gel process. 63, 2012, 251–257 (© Springer Science + Business Media, LLC 2012). With the permission of Springer.

Figure 7

Photomicrograph of a lamellar liquid crystal (containing 10% C12-25 acid PEG-8 ester as emulsyfing agent), with the presence of a Maltese cross. Magnified 40×.

Figure 8

The six types of adsorption isotherm: (I) microporous; (II and III) macroporous; (IV and V) mesoporous; and (VI) non-porous materials.

Figure 9

SAXS curves of the systems developed by Negrini et al, showing the reversibility of the mesophase following pH changes (pH 7 [lower curve] → pH 2 [middle curve] → pH 7 [upper curve]). Adapted with permission, from: Negrini R, Mezzenga R, pH-responsive lyotropic liquid crystals for controlled drug delivery. Langmuir 27(9), 2011, 5296–5303. Copyright 2017 American Chemical Society.

Figure 10

Cryo-TEM images of HA-liposomes (A) and HA-liposomes containing siRNA (B) developed by Nascimento et al (scale bars: 200 nm). (C) SAXS curves of liposomes and HA-liposomes with different percentages of HA. Adapted with permission, from: Nascimento TL, Hillaireau H, Noiray M, et al. Supramolecular organization and siRNA binding of hyaluronic acid-coated lipoplexes for targeted delivery to the CD44 receptor. Langmuir 31(41), 2015, 11186–11194. Copyright 2017 American Chemical Society. Abbreviation: HA-DOPE, hyaluronic acid inserted in dioleylphosphatidylethanolamine.