Comblike Ionic Complexes of Hyaluronic Acid and Alkanoylcholine Surfactants as a Platform for Drug Delivery Systems

Abstract

Nontoxic alkanoylcholine soaps ( nACh) were synthesized from choline and fatty acids with numbers of carbons n equal to 12, 14, 16, and 18, the latter including both saturated and 9- cis unsaturated alkanoyl chains. Coupling of nACh with hyaluronic acid (HyA) rendered comblike ionic complexes nACh·HyA that were non-water-soluble. The complexes were thermally stable up to temperatures above 200 °C but readily degraded by water, in particular when hyaluronidases were present in the aqueous medium. In the solid state, these complexes were self-assembled in a biphasic layered structure in which the surfactant and the polysaccharide phases were alternating regularly with a periodicity dependent on the length of the alkanoyl chain. The paraffinic phase was found to be crystallized in saturated complexes with n ≥ 14, but only 18ACh·HyA showed reversible melting crystallization when subjected to cyclic heating-cooling treatment. Nanoparticles with diameters in the 50-150 nm range were prepared by ionotropic gelation from unbalanced 18ACh·HyA complexes with surfactant:HyA ratios of 0.5 and 0.25. These nanoparticles were also structured in layers, swelled slowly in water, and shown to be noncytotoxic in in vitro assays against macrophages cells. It was also shown that the anticancer drug doxorubicin was efficiently encapsulated in both films and NPs of 18ACh·HyA, and its release was shown to be almost linear and complete after one day of incubation in physiological medium. The nACh·HyA complexes constitute a highly promising biocompatible/biodegradable platform for the design of systems suitable for drug transport and targeting delivery in anticancer chemotherapy.

Polyelectrolyte–Surfactant Complexes As a Formulation Tool for Drug Delivery

“…The insoluble complexes can be processed into thin films, and both of these films and the nanoparticles can be loaded with the anticancer drug doxorubicin. 70 The importance of forming PESCs was also demonstrated for the case of chitosan-based complexes that are able to solubilize doxorubicin and zoledronic acid and where the presence of the polymer surfactant F127 was found to be crucial in forming the small and monodisperse aggregates required for delivery purposes. 71 In a recent study, PESCs composed of alginate and cetylpyridinium chloride (CPC) were employed for solubilizing ibuprofen, a standard drug for pain suppression, and an aromatic acid (isobutylphenylpropionic acid).…”

“…For equimolar mixing they formed water-insoluble complexes, but for addition of smaller amounts of surfactant, dispersed nanoparticles with diameters of 50–150 nm were formed, where locally layered structures are always present. The insoluble complexes can be processed into thin films, and both of these films and the nanoparticles can be loaded with the anticancer drug doxorubicin …”

Structure–Dilute Solution Property Relationships of Comblike Macromolecules in a Good Solvent

“…This lack of understanding makes it difficult to characterize structure−property relationships for comblike macromolecules that have applications in numerous novel technologies, such as photonic crystals, 5 chemotherapy, 6 and drug delivery. 7 These applications do not consider less novel but industrially important comblike polymers such as linear low-density polyethylene (LLDPE), which combined with lowdensity polyethylene (LDPE) comprises 16% of the plastics market worldwide. 8 The popularity of LLDPE in applications from food packaging to playgrounds stems from its flexibility compared to high-density polyethylene (HDPE) and its improved stress-crack resistance, puncture resistance, and optical clarity compared to LDPE.…”

“…While prior work demonstrates this effect typically leads to a decrease in the dilute solution properties at a given molar mass, − these expectations do not constitute a complete theory. This lack of understanding makes it difficult to characterize structure–property relationships for comblike macromolecules that have applications in numerous novel technologies, such as photonic crystals, chemotherapy, and drug delivery . These applications do not consider less novel but industrially important comblike polymers such as linear low-density polyethylene (LLDPE), which combined with low-density polyethylene (LDPE) comprises 16% of the plastics market worldwide .…”