Low temperature, easy scaling up method for development of smart nanostructure hybrid lipid capsules for drug delivery application

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2020-06, Vol.190, p.110927, Article 110927
• Main Authors: Yadava, Sunil Kumar, Basu, Suparna Mercy, Chauhan, Meenakshi, Sharma, Kshipra, Pradhan, Arpan, V., Remya, Giri, Jyotsnendu
• Format: Article
• Language: English
• Subjects: Biocompatible Materials - chemistry; Capsules - chemistry; Drug delivery; Drug Delivery Systems; Lipid nanocapsules (LNCs); Lipids - chemistry; Nanostructure hybrid lipid capsules (nHLCs); Nanostructures - chemistry; Particle Size; Phenylurea Compounds - chemistry; Pyridines - chemistry; Regorafenib; Self-assembling; Surface Properties; Temperature
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2020.110927

[Display omitted] •Developed a novel low temperature method to fabricate nHLCs.•nHLCs are core-shell systems composed of oil, phospholipids and surfactant.•The size of capsules can be adjusted from 25 to 150 nm.•The shell made of phospholipids, can be tuned for pH/Temp. responsive property.•nHLCs are capable of delivering high payloads in a controlled release fashion. Lipid Nanocapsules (LNCs) have been used for drug delivery in cells and animal models for several years. LNCs with unique physicochemical properties for favorable biorecognition, biocompatibility and stimuli responsive (pH/temperature etc.) properties i.e., smart-LNCs, are most promising for future nanomedicine applications. However, conventional phase inversion temperature (PIT) method of LNCs preparation may not be suitable for the fabrication of thermally labile drug loaded LNCs and smart-LNCs. Herein, we report for the first time, a novel low temperature (LT) method for the preparation of LNCs (including smart-LNCs of size 25–150 nm), hereafter, named as nanostructure hybrid lipid capsules (nHLCs), comprising safe excipients such as oil (Labrafac™ PG), surfactant (Kolliphor® HS 15, Brij® S100), and lipid (Lipoid S-75, Lipoid S PC-3, Lipoid PE 18:1/18:1, Lipoid PC 16:0/16:0 etc.). Effects of process parameters on the physicochemical properties of nHLCs were probed to optimize the process. Ternary phase diagram shows that our method allows for great flexibility in the formation of nHLCs with tailored size and composition. This method resulted in drug loaded (regorafenib used as model drug) nHLCs with 95 % encapsulation efficiency and sustained release profile at 37 °C. The drug loaded nHLCs (as prepared or in lyophilized form) has excellent storage stability at 4 °C (for more than one month) as well as biocompatibility similar to that of LNCs prepared by PIT method. Our novel LT method of LNCs (i.e. nHLCs) preparation is a generic method for the development of drug loaded (including thermally labile) and smart-LNCs for future nanomedicine applications.