PEG-coumarin nanoaggregates as π–π stacking derived small molecule lipophile containing self-assemblies for anti-tumour drug delivery

Abstract

Polymeric self-assemblies formed by non-covalent interactions such as hydrophobic interactions, hydrogen bonding, π-π stacking, host-guest and electrostatic interactions have been utilised widely and exhibit controlled release of encapsulated drug. Beside carrier-carrier interactions, small molecule amphiphiles exhibiting carrier-drug interactions have recently been an area of interest for cancer drug delivery, as most of the hydrophobic anti-tumour drugs are aromatic and exhibit π-π conjugated structure. In the present study PEG-coumarin (PC) conjugates forming self-assembled nanoaggregates were synthesised with PEG (polyethylene glycol) as hydrophilic block and coumarin as small molecule lipophilic segment. Curcumin (CUR) as model conjugated aromatic drug was loaded in to the nanoaggregates via dual hydrophobic and π-π stacking interactions. The interactions between the conjugates and CUR, drug release profile and in vitro anti-tumour efficacy were investigated in detail. CUR-loaded nanoaggregate self-assembly was driven by π-π interactions and a maximum loading level of about 18 wt.% (~60 % encapsulation efficiency) was achieved. The average hydrodynamic diameter (D) was in the range of 120-160 nm and a spherical morphology was observed by transmission electron microscopy (TEM). A sustained release of CUR was observed for 90 h. Cytotoxicity evaluation of CUR-loaded nanoaggregates on pancreatic cancer cell lines indicated higher efficacy, IC ~11 and ~15 μM as compared to free CUR, IC ~14 and ~20 μM on human pancreatic carcinoma (MIA PaCa-2) and human pancreatic duct epithelioid carcinoma (PANC-1) cell lines respectively. PC conjugates provided a new strategy of fabricating nanoparticles for drug delivery and may form the basis for the development of advanced biomaterials in near future.

Formulation Strategies for Folate-Targeted Liposomes and Their Biomedical Applications

“…A number of therapeutics, including paclitaxel (PTX) [105,106], doxorubicin (DOX) [107,108], methotrexate [109,110], cis-platin [111,112], curcumin [113,114], 5-fluorouracil [115,116], irinotecan [117,118], and nucleic acids [119,120], have been delivered via polymeric carriers [121] to cells. However, liposomes provide unique properties, as their charge, size, and surface properties can easily be tuned by selecting different ingredients of lipid mixture prior to the preparation of the liposomes.…”

Physicochemical Properties of a New PEGylated Polybenzofulvene Brush for Drug Encapsulation

“…Interestingly, we assumed that the presence of MOEG-9 SC in benzofulvene monomer 6-MOEG-9-T- BF3k led to the formation of amphiphilic molecules, which could be capable in principle of self-assembling in water solutions to form micelles. The hydrophobic nature of the 3-phenylbenzofulvene moieties could drive the aggregation [39,40,41] leading to the exposition of the MOEG-9 SC to the water environment [42]. In this organization, the recognition process and the following spontaneous polymerization could occur inside the core of the micelles [12,13].…”

Redox-Responsive Core-Cross-Linked Micelles of Miktoarm Poly(ethylene oxide)-b-poly(furfuryl methacrylate) for Anticancer Drug Delivery

“…The product was characterized by Fourier transform infrared (FTIR), 1 H NMR, and gel permeation chromatography (GPC) (Table 1 (5 g, 2.5 mmol, 1 equiv) was added dropwise to a dispersion of NaH (65.95 mg, 2.75 mmol, 1.1 equiv, 60% w/w in mineral oil) in 80 mL of dry THF at RT. 29,30 After the gas evolution stopped, propargyl bromide (0.28 mL, 2.75 mmol, 1.1 equiv, 80% in toluene) was added and stirred for 20 h. The solvent was then evaporated, and the crude product was dissolved in ethyl acetate (150 mL) and passed through a silica gel column. The solvent was removed, and the residue was dried under vacuum to yield the product (3.67 g, 1.8 mmol, 72%).…”