Fabrication of oligo‐glycerol based hydrolase responsive amphiphilic nanocarriers

Abstract

Herein, we report on the synthesis of a new class of novel non-ionic amphiphiles using triglycerol as a core, which is further functionalized with hydrophilic units poly(ethylene glycol) monomethyl ether (M n : 350 and 550) and a pair of hydrophobic alkyl chains (C 18 or C 15 ) via chemo-enzymatic approach. Fluorescence measurements and dynamic light scattering studies showed that all of the synthesized amphiphilic systems spontaneously self-assemble in aqueous solution, which is further confirmed by the transmission electron microscopy. Encapsulation of hydrophobic moieties like Nile red and nimodipine was studied using ultraviolet-visible (UV-vis) and fluorescence spectrometer techniques. A cytotoxicity study of the amphiphiles using A549, HeLa, and MCF7 cell, which showed that all of the synthesized nanocarriers are well tolerated at the concentrations studied. The release profile of encapsulated Nile red in synthesized amphiphilic system was studied in the presence of the immobilized enzyme (Novozym 435).amphiphile, cytotoxicity, encapsulation, self-assembly 1 | INTRODUCTION Molecular self-assembly, the spontaneous process of forming ordered aggregates without external intervention is gaining attention by researchers from different disciplines because of its widespread applications. The phenomenon is derived mostly by various noncovalent interactions such as hydrophobic, ionic, π-π stacking, and electrostatic interaction adopting the minimal Gibbs free energy and thermodynamic stability. 1-4 The natural self-assembly phenomenon, for example, polypeptide chains folding into proteins or conformational changes of nucleic acids into their different functional forms etc, have inspired the scientific community to mimic the process using newly designed molecules. 5,6 Self-assembly of amphiphilic macromolecules provide a unique and newer opportunity for designing novel material for advanced applications in biomedicine and bionanotechnology. 7-11 Among the diverse and various promising applications of amphiphilic macromolecules, the area of drug delivery is challenging because of the limited aqueous-solubility and short circulation half-life of most clinically used drugs. [12][13][14] Carrier-mediated drug delivery not only can maximize the bioavailability but also allow targeting the active site in the body while minimizing the side effects.Amphiphiles can self-assemble into a variety of nano and microscale structures in the aqueous medium, where the majorly known 3-D structures include vesicles, micelles, and molecular gels. [15][16][17] Micelles vary in diameter in the range of 5 to 100 nm and may consist of spheres, discs, and wormlike assemblies, 18 whereas vesicles are found in hollow, spherical, and lamellar type morphologies within the diameter range of 20 nm to micrometer. 19 Since micelles formed by small molecules have simple synthesis, high loading capacity, and low toxicity, they may be able to target many cancer tissues and ensure the accumulation within the small vasculatures of tumors. 20,21 However, o...

Oligo-glycerol based non-ionic amphiphilic nanocarriers for lipase mediated controlled drug release

“…The HLB value of all the amphiphiles was evaluated by the Griffin equation (Table 1). Furthermore, a comparison of these diaryloxydiglycerol based amphiphiles (15 and 16) having lower CAC with the previously reported triaryloxytriglyceryl analogue 19/20 synthesized by earlier reported method 35 shows that on moving from triaryloxytriglycerol spacer to diaryloxydiglycerol spacer reduces the CAC (Fig. 2 and Table 1) and this improvement in CAC may be because of proper structural balance of hydrophobic and hydrophilic segments.…”

“…Structure of (a) diaryloxydiglycerol based and (b)35 triaryloxytriglycerol based amphiphilic architectures.…”

Non-ionic small amphiphile based nanostructures for biomedical applications

“…A novel-class of triglycerol based hydrolase responsive amphiphilic architectures were synthesized by using PEG as hydrophilic unit and alkyl chain (C 15 and C 18 ) as hydrophobic part, and employing chemo-enzymatic approach. 64 Fluorescence measurements and DLS studies showed that all the amphiphiles self-assembled in aqueous medium with low CAC in the order of 10 À5 M and DLS size in the range of 8-10 nm. Among all, amphiphiles having higher HLB value encapsulated the highest amount of drug nimodipine and dye nile red.…”

Self-assembly of carbohydrate-based small amphiphiles and their applications in pathogen inhibition and drug delivery: a review

“…Our research group has been involved in the synthesis of advanced nanocarriers for drug delivery applications. We have synthesized numerous polymeric, 50-52 dendritic 48 and small amphiphilic architectures [53][54][55][56][57] for the encapsulation of various drugs and dyes. In one of our research works, water-soluble dendritic architectures having a symmetrical aromatic core, hydrophobic alkyl chain branches and glucose as hydrophilic surface groups were reported (Fig.…”