Structural Characterization Study of a Lipid Nanocapsule Formulation Intended for Drug Delivery Applications Using Small-Angle Scattering Techniques

Abstract

Lipid nanocapsules (LNCs) are increasingly being used for various drug delivery applications due to their versatile nature and ability to carry a wide variety of therapeutic drug molecules. In the present investigation, small-angle X-ray (SAXS) and neutron scattering (SANS) techniques were used to elucidate the structure of LNCs. Overall, size measurements obtained from SAXS and SANS techniques were complemented with dynamic light scattering, zeta potential, and cryogenic transmission electron microscopy measurements. The structural aspects of LNCs can be affected by drug loading and the properties of the drug. Here, the impact of drug loading on the overall structure was evaluated using DF003 as a model drug molecule. LNCs with varying compositions were prepared using a phase inversion method. Combined analysis of SAXS and SANS measurements indicated the presence of a core–shell structure in the LNCs. Further, the drug loading did not alter the overall core–shell structure of the LNCs. SANS data revealed that the core size remained unchanged with a radius of 20.0 ± 0.9 nm for unloaded LNCs and 20.2 ± 0.6 nm for drug-loaded LNCs. Furthermore, interestingly, the shell becomes thicker in an order of ∼1 nm in presence of the drug compared to the shell thickness of unloaded LNCs as demonstrated by SAXS data. This can be correlated with the strong association of hydrophilic DF003 with Kolliphor HS 15, a polyethylene glycol-based surfactant that predominantly makes up the shell, resulting in a drug-rich hydrated shell.

Nanotherapeutic Heterogeneity: Sources, Effects, and Solutions

“…[307] Small angle X-ray or neutron scattering (SAXS or SANS, respectively) are two other powerful techniques for understanding heterogeneities in nanotherapeutics' internal structure, e.g., the core diameter and shell thickness of lipid nanocapsules. [308,309] For a more comprehensive review of singleparticle analysis techniques we refer to the works of Yan et al [310] and Ramassamy et al [25] Enhanced insight into nanotherapeutic heterogeneity will also require more uniform and thorough reporting strategies. [311] For instance, DLS-based nanotherapeutic size measurements are conducted in diverse media, and the reporting manuscripts often do not specify if the number-, volume-, or intensity-based average is being disclosed.…”

“…[ 307 ] Small angle X‐ray or neutron scattering (SAXS or SANS, respectively) are two other powerful techniques for understanding heterogeneities in nanotherapeutics’ internal structure, e.g., the core diameter and shell thickness of lipid nanocapsules. [ 308,309 ] For a more comprehensive review of single‐particle analysis techniques we refer to the works of Yan et al. [ 310 ] and Ramassamy et al.…”

Advances in nanomedicines for lymphatic imaging and therapy

“…Nanocapsules are a newly developed lymphatic system nanodrug delivery carrier in recent years. Due to the controllable capsule size, distribution particle size, and good biocompatibility, they have been widely used in the development of lymphatic targeted drug delivery platforms for drug control release and antigen and adjuvant delivery [ 92 , 93 ]. Research found that small-sized (100 nm) polyamino acid nanocapsules have better lymphatic absorption and biological distribution characteristics.…”

Lipid and Transcriptional Regulation in a Parkinson's Disease Mouse Model by Intranasal Vesicular and Hexosomal Plasmalogen‐Based Nanomedicines

“…[1][2][3][4][5][6][7] Phospholipids comprise bioactive agents, exerting a variety of therapeutic effects, as well as supramolecular-structure-forming materials, which interact with the biological barriers. [8][9][10] Lipid nanoparticles (LNPs), a class of nanometric drug delivery systems, have been successfully used in the development of anti-coronavirus vaccines and as reservoirs for the controlled delivery of various bioactive compounds. [11][12][13] In fact, encapsulating therapeutic molecules within LNPs helps enhance their bioavailability and stability, reducing the drug dose, and avoiding severe side effects.…”