Development of a Nanostructured Lipid Carrier (NLC) by a Low-Energy Method, Comparison of Release Kinetics and Molecular Dynamics Simulation

Abstract

Lipid nanocarriers have a great potential for improving the physicochemical characteristics and behavior of poorly water-soluble drugs, such as aqueous dispersibility and oral bioavailability. This investigation presents a novel nanostructured lipid carrier (NLC) based on a mixture of solid lipid glycerides, fatty acid esters of PEG 1500 (Gelucire® 44/14), and an oil mix composed of capric and caprylic triglycerides (Miglyol® 812). These NLCs were developed by a simple low-energy method based on melt emulsification to yield highly encapsulating and narrowly distributed nanoparticles (~100 nm, PdI = 0.1, and zeta potential = ~−10 mV). Rhodamine 123 was selected as a poorly water-soluble drug model and owing to its spectroscopic properties. The novel NLCs were characterized by dynamic light scattering (DLS), zeta potential, nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and colloidal stability. The drug release was determined through a dialysis bag and vertical Franzs’ cells to provide insights about the methods’ suitability, revealing similar performance regardless of their different fluid dynamics. Rhodamine 123 followed a characteristic biphasic release profile owing to the swelling of the hydrophilic polymer coating and diffusion process from the lipid core as revealed by the Korsmeyers–Peppas kinetic modeling. Moreover, to elucidate the formation and incorporation of Rhodamine 123 into the NLC core, several molecular dynamics simulations were conducted. The temperature was shown to be an important condition to improve the formation of the nanoparticles. In addition, the liquid lipid incorporation to the formulation forms nanoparticles with imperfect centers, in contrast to nanoparticles without it. Moreover, Miglyol® 812 improves hydrophobic molecule solubility. These results suggest the potential of novel NLC as a drug delivery system for poorly water-soluble drugs.

Tunable Polymeric Mixed Micellar Nanoassemblies of Lutrol F127/Gelucire 44/14 for Oral Delivery of Praziquantel: A Promising Nanovector against Hymenolepis nana in Experimentally-Infected Rats

“…Remarkably, GL44 comprises 72% PEG with an HLB value of 14, hence once PEG is beneath the threshold, PRZ-PMMs should elicit adequate stability. Furthermore, GL44 molecules experience self-aggregation at higher levels, which could give a share in the dropping of PRZ EE% [ 49 ]. Such results are endorsed with prior literature arts [ 20 , 47 , 48 ].…”

“…Likewise, GL44 concentration ( X 2 ) exerted a biphasic influence on the mean micelle size of the tailored PRZ-PMMs ( p < 0.0001), Figure 1 b. Initially, the increment in GL44 level resulted in a synchronous reduction in the micellar size which might be inferred from stronger hydrophobic interactions among PPO domains of LF127 and the hydrophobic moiety of GL44 within the micellar core and/or diminution of interfacial tension via GL44 surface active characteristics lowering surface free energy with ultimate generation of compact micelles [ 49 ]. Furthermore, the enlarging tendency of micellar size with the subsequent increment in GL44 concentration could be imputed to distension of micellar corona due to the amplified number of PEG domains of GL44 relative to its hydrophobic portion [ 55 ].…”

Green Extraction of Annatto Seed Oily Extract and Its Use as a Pharmaceutical Material for the Production of Lipid Nanoparticles

“…New colloidal systems based on myristic acid esters (methyl tetradecanoate (MT), ethyl tetradecanoate (ET), isopropyl tetradecanoate (IT), and butyl tetradecanoate (BT)) were produced, and evaluated. The esters of long-chain fatty acids contribute to the formation of nanoemulsions (Nn), i.e., nano-liquid or semi-solid droplets, and improve their encapsulation capacity and stability of Nn by steric interaction, hydration in the surface layer, and resistance to flocculation and coalescence preparation of Nn [42]. For example, a mixture of Precirol ATO 5 and a fatty alcohol or fatty acid ester was a successful strategy for Nn production [43].…”

Physicochemical Characteristics, Stability, and Irritability of Nanostructured Lipid Carrier System Stabilized with Different Surfactant Ratios

“…NLC presents many other advantages such as the improved penetration of drugs due to the increased permeation on the skin and the occlusive effect while decreasing the transepidermal water loss and increasing skin hydration (Pivetta et al, 2018). Thus, NLC formulations have been proposed to be suitable for cosmeceuticals, especially for poorly watersoluble (Ortiz et al, 2021) and weak-acid drugs (Rahmasari, 2018).…”

“…The surfactant concentration is one of the important factors that affect the stability, particle size, particle size, particle size distribution, degree of crystallization, and polymorphism of the Nanostructured Lipid Carrier (NLC). The surfactant acts as a stabilizer (Ortiz et al, 2021), and plays an important role in lipid nanoparticles formation. Surfactant reduces the surface tension and facilitates the particle partition during the homogenization process (de Souza et al, 2021).…”