Microfluidic Fabrication of Physically Assembled Nanogels and Micrometric Fibers by Using a Hyaluronic Acid Derivative

Abstract

The employ of a hyaluronic acid (HA) derivative, bearing octadecyl (C18) and ethylenediamine (EDA) groups, for microfluidic fabrication of nanogels and microfibers is reported in this study. Two HA‐EDA‐C18 derivatives (125 and 320 kDa) having ionic strength sensitive properties are synthesized and characterized. The control of the rheological properties of HA‐EDA‐C18 aqueous dispersions by formation of inclusion complexes with hydroxypropyl‐β‐cyclodextrins (HPCD) is described. Reversibility of C18/HPCD complexation and physical crosslinking is detected in media with different ionic strength through oscillation frequency tests. HA‐EDA‐C18 125 kDa is employed for nanogel fabrication. Control over nanogel dimension by flow ratio regulation is demonstrated. HA‐EDA‐C18 320 kDa with HPCD is employed for fabrication of both microfibers and microchannels. Dimension of fibers is controlled by modulating flow ratios. Suitability for biological functionalization is assayed introducing cell adhesive peptides. Adhesion and encapsulation of human umbilical vein endothelial cells is evaluated.

Imatinib-Loaded Micelles of Hyaluronic Acid Derivatives for Potential Treatment of Neovascular Ocular Diseases

“…Ultraviolet (UV) measurements were carried out by using a Shimadzu UV-2401PC spectrophotometer. Gel permeation chromatography (GPC) was performed by using an Agilent 1260 Infinity Multi-Detector Bio-SEC solution, as reported elsewhere . GPC system was equipped with a pump system, a PolySep-GFC-P 4000 column from Phenomenex, Bio-Dual Angle LS/DLS, and RI Detector.…”

“…This biopolymer is able to increase the time of corneal contact of the aqueous formulations, reduce the loss of drugs, and improve their bioavailability . Furthermore, HA can be chemically modified to obtain derivatives that can be used both in regenerative medicine and drug delivery fields. − In particular, the synthesis and characterization of an amphiphilic derivative of hyaluronic acid containing ethylenediamine (EDA) and hexadecyl groups (C 16 ), called HA-EDA-C 16 , were reported here. EDA was used to insert primary amine groups on HA backbone that are useful for additional functionalization.…”

Synthesis of Nanogels: Current Trends and Future Outlook

“…Although alginate has gained far more attention given its unique features such as ease of gelation and biocompatibility, to date, various kinds of polymeric NGs have been obtained through microfluidic-based approaches. Among the most notable examples, Agnello and collaborators [140] employed hyaluronic acid (HA) derivatives, functionalized with octadecyl and ethylenediamine moieties to produce nanostructures by modulating its self-assembly into a split-and-recombine micromixer. The peculiar property of the obtained HA-based specimens lies in the responsive behavior to the ionic strength, which can be exploited to produce a controlled coacervation of the polymer when mixed with aqueous salt solutions.…”

Nanogels for Pharmaceutical and Biomedical Applications and Their Fabrication Using 3D Printing Technologies

“…Especially for hydrogel production, it is well known that microfluidic systems offer excellent controls in size, morphology and, importantly, straightforward scale-up capabilities to produce hydrogels at an industrial scale. Subsequently, there are a number of reports showcasing unique modifications of a microfluidic system to prepare nanogels in a highly-controllable manner [ 26 , 27 , 28 ]. For example, Agnello et al employed hyaluronate XS-ethylenediamine-C 18 dispersions for the production of nanogels using a micromixer microfluidic chip [ 27 ].…”

“…Subsequently, there are a number of reports showcasing unique modifications of a microfluidic system to prepare nanogels in a highly-controllable manner [ 26 , 27 , 28 ]. For example, Agnello et al employed hyaluronate XS-ethylenediamine-C 18 dispersions for the production of nanogels using a micromixer microfluidic chip [ 27 ]. The nanogels prepared were further lyophilized.…”