UV‐Photocrosslinking of Inulin Derivatives to Produce Hydrogels for Drug Delivery Application

Abstract

In this work, INU, a natural polysaccharide, has been chemically modified in order to obtain new photocrosslinkable derivatives. To reach this goal, INU has been derivatized with MA thus obtaining four samples (INU-MA derivatives) as a function of the temperature and time of reaction. An aqueous solution of the derivative INU-MA1 was irradiated by using a UV lamp with an emission range from 250 to 364 nm and without using photoinitiators. The obtained hydrogel showed a remarkable water affinity but it underwent a partial degradation in simulated gastric fluid. To overcome this drawback, INU-MA1 was derivatized with SA thus obtaining the INU-MA1-SA derivative designed to produce a hydrogel showing a low swelling and an increased chemical stability in acidic medium. Ibuprofen, as a model drug, was loaded by soaking into INU-MA1 and INU-MA1-SA hydrogels and its release from these matrices was evaluated in simulated gastrointestinal fluids. INU-MA1 hydrogel showed the ability to quickly release the entrapped drug thus indicating its potential as a matrix for an oral formulation. INU-MA1-SA hydrogel showed a pH-responsive drug delivery. Therefore it is a promising candidate for controlled drug release in the intestinal tract.

Hydrogels for Potential Colon Drug Release by Thiol‐ene Conjugate Addition of a New Inulin Derivative

“…Finally, the introduction of succinated groups allows us to confer pH sensitivity to the resulting hydrogel. Since in previous studies we have found that the reaction between hydroxyl groups of INU and SA is almost quantitative at 25 8C for 24 h, [4,7] we chose to use a molar ratio between SA and INU repeating units equal to 0.5, in order to obtain a derivative containing a suitable amount of succinated groups to maintain a good balance between water solubility and pH sensitivity.…”

“…The application of hydrogels ranges over many fields: they have been proposed for use in the food industry, [1] as drug delivery systems, [2][3][4][5] biomaterials in tissue engineering and, most generally, in biomedical applications. [6,7] Hydrogels can be prepared from natural, [4,[8][9][10] synthetic [2,3,11] and mixed natural/synthetic polymers. [5,12,13] Hydrogels made from natural polymers offer several advantageous properties, such as native biocompatibility, biodegradability and biologically recognizable moieties that support cellular activities.…”

“…Hydrogels made from synthetic polymers, on the other hand, generally, do not possess these native bioactive properties, but usually they have well-defined structures that can be modified to reach the wanted degradability and functionality. The strategies employed to obtain chemically crosslinked hydrogels are numerous, from conjugation of a polymer functional group with a complementary reagent, [14] to UV induced crosslinking of acrylic functionalized polymers, [4,5,15] to addition of electron bearing moieties (such as thiol, amine or nitrile groups both bi or multifunctional), to acceptor molecules such as acrylic or vinyl sulfone groups. [16][17][18][19][20][21][22][23] In particular, the vinyl sulfone group is receiving growing attention, in organic synthesis, as a selective electron acceptor in the formation of new heteroatom/carbon bonds.…”

“…In particular, the choice of inulin as a starting polymer was based on the peculiar properties of this polysaccharide; it is specifically degraded into the colon, non-toxic (including its degradation products), shows a prebiotic effect on the intestinal bacterial population, is widely used in the food industry, is FDA approved and has been proposed as a starting material for the production of drug delivery systems. [4,7,[29][30][31][32][33][34][35][36][37][38][39] Taking into consideration the interesting physicochemical properties of INUDVSA-TT hydrogels, such as cell compatibility, pH-sensitivity and biodegradability, they were soaked with 2-metoxyestradiol (2-ME), chosen as an anti-cancer model drug. 2-ME is an endogenous metabolite of estrogen, which is synthesized in vivo by hydroxylation at the 2-position of 17b-estradiol by cytochrome P450 enzymes, and subsequent catechol-O-methyltransferase (COMT) mediated O-methylation.…”

Photocrosslinkable Polymers for Biomedical Applications

“…These modifications allow us to improve some of their assets such as hemo and biocompatibility. It is also possible, by using radiation, to prepare crosslinked systems that may be used to encapsulate cells (Cruise et al, 1999;Hill et al, 1997;Li et al, 2006), proteins (Leach et al, 2005) or other compounds to be controlled delivered (Vieira et al, 2008;Tripodo et al, 2005). In the following sections a literature review in some of the possible applications of photocrosslikable polymers will be presented.…”