https://dash.harvard.edu/bitstream/handle/1/29005173/Formulation%20of%20Functionalized%20PLGA-PEG.pdf?sequence=1

Formulation of functionalized PLGA-PEG nanoparticles for in vivo targeted drug delivery

A protein which exhibits a therapeutic effect on inflammation and is useful for treating IL-1-mediated inflammatory diseases, particularly diseases of the joint.

Composition and method for treating inflammatory diseases

In recent studies, we showed that exogenous hyaluronic acid oligomers (HA-o) stimulate functional endothelialization, though native long-chain HA is more bioinert and possibly more biocompatible. Thus, in this study, hydrogels containing high molecular weight (HMW) HA (1 x 10(6) Da) and HA-o mixtures (HA-o: 0.75-10 kDa) were created by crosslinking with divinyl sulfone (DVS). The incorporation of HA-o was found to compromise the physical and mechanical properties of the gels (rheology, apparent crosslinking density, swelling ratio, degradation) and to very mildly enhance inflammatory cell recruitment in vivo; increasing the DVS crosslinker content within the gels in general, had the opposite effect, though the relatively high concentration of DVS within these gels (necessary to create a solid gel) also stimulated a mild subcutaneous inflammatory response in vivo and VCAM-1 expression by endothelial cells (ECs) cultured atop; ICAM-expression levels remained very low irrespective extent of DVS crosslinking or HA-o content. The greatest EC attachment and proliferation (MTT assay) was observed on gels that contained the highest amount of HA-o. The study shows that the beneficial EC response to HA-o and biocompatibility of HA is mostly unaltered by their chemical derivatization and crosslinking into a hydrogel. However, the study also demonstrates that the relatively high concentrations of DVS, necessary to create solid gels, compromise their biocompatibility. Moreover, the poor mechanics of even these heavily crosslinked gels, in the context of vascular implantation, necessitates the investigation of other, more appropriate crosslinking agents. Alternately, the outcomes of this study may be used to guide an approach based on chemical immobilization and controlled surface-presentation of both bioactive HA-o and more biocompatible HMW HA on synthetic or tissue engineered grafts already in use, without the use of a crosslinker, so that improved, predictable, and functional endothelialization can be achieved, and the need to create a mechanically compliant biomaterial for standalone use, circumvented.

The impact of hyaluronic acid oligomer content on physical, mechanical, and biologic properties of divinyl sulfone-crosslinked hyaluronic acid hydrogels.

Characterization of glycidyl methacrylate - crosslinked hyaluronan hydrogel scaffolds incorporating elastogenic hyaluronan oligomers.

Characterization and comparison of shear and extensional flow of sodium hyaluronate and human synovial fluid.

Since its discovery from bovine synovial fluid, hyaluronic acid has found application in several diverse areas It is now extensively used in ophthalmic surgery, in the treatment of lameness in racehorses and as an ingredient in cosmetics It can also be used in drug delivery, orthopedics, cardiovascular aids and in wound healing Even so, its potential as a therapeutic agent is yet to be fulfilled New improved products, formed by crosslinking hyaluronic acid with itself or other chemicals, are being produced Hyaluronic acid is clearly a most valuable therapeutic biopolymer This article reviews the properties of hyaluronic acid, its biosynthetic pathway and its methods of commercial production, and provides an estimation of its current and future world demand Experiments designed to improve production economics have been performed in our laboratory These involved control of glucose and yeast extract concentrations and fermentation pH Hyaluronic acid production by Streptococcus zooepidemicus was found to be lower at pH 65 than at pH 71 A new method of extending the production of hyaluronic acid by S zooepidemicus into the stationary phase has also been achieved

Hyaluronic acid--a versatile biopolymer.

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Hyaluronic acid--a versatile biopolymer.