GELS STRUCTURE LIQUID PHASE CROSSLINKS POLYMERIC CHAINS MATRICES ARE COHERENT SYSTEMS MADE UP BY A POLYMERIC NETWORK TRAPPING A CONTINUOUS LIQUID PHASE. THEY SHOW MECHANICAL PROPERTIES IN BETWEEN THOSE OF SOLIDS AND LIQUIDS

Schneider et al. J. American Chemical Society, 2002. 20 mm 0.2 mm Schneider et al. J. American Chemical Society, 2002. (a) Laser scanning confocal microscopy. Green regions are fluorescently stained self-assembled peptide, and black regions are water-filled pores and channels. (b) CryoTEM. Dark structures are selfassembled peptide scaffold, while lighter gray areas are composed of vitrified water.

PHYSICAL CROSSLINKS (weak) ENTANGLEMENTS (TOPOLOGICAL CONSTRAINS) ORDERED ZONES CONNECTING DISORDERED ZONES Van der Walls, dipole-dipole, hydrogen bonding, Coulombic hydrophobic interactions POLYSACCARIDES (GLUCANS, XANTHAN)

INTERACTION BETWEEN THE BIVALENT ION AND GULURONIC UNIT PHYSICAL CROSSLINKS (strong) Ca++ EGGS BOX STRUCTURE Ca++ INTERACTION BETWEEN THE BIVALENT ION AND GULURONIC UNIT ALGINATES

CHEMICAL CROSSLINKS (strong: covalent bond) SCLEROGLUCAN CROSSLINKED WITH BORAX T. Coviello et al., Int. J. Biol. Macromolecules, 32 (2003) 83

POROUS GELS: Cellulose – Acrylic Acid Crosslinking irradiation intensity Cellulose mass fraction Acrylic acid mass fraction

Surface picture (406035) (ESEM)

Cross-section picture (406035) (ESEM)

Surface picture (208035) (ESEM)

Cross-section picture (208035) (ESEM)

GEL SUPERPOROSI

SPH SAP a) Monomer dilution c) Crosslinker b) Neutralization d) Foaming aid and stabilizer e) Oxidant f) Reductant g) Bicarbonate SPH a) Monomer dilution e) Oxidant thermal initiator b) Neutralization f) Reductant c) Crosslinker d) Foaming aid g) Bicarbonate SAP Figure 6.2. Schematic representation of steps involved in the production of Super porous hydrogels (SPH) and Super absorbent polymers (SPA) (with permission from ref.[46]).

POROSITA’ RD/RP 0.01 0.1 MEZZO CONTINUO MEZZO POROSO ZONA INTERMEDIA Il moto del farmaco avviene tra le maglie del reticolo polimerico contenenti anche le molecole del fluido di rilascio MEZZO POROSO CATENE POLIMERICHE FARMACO Il moto del farmaco avviene nel fluido di rilascio che riempe i canali le cui pareti sono costituite dal polimero RD/RP 0.01 0.1 ZONA INTERMEDIA

R = 0 R = Rp De = Dw *e/t DIFFUSIONE DRUG TORTUOSITA’ Lc/Rp POROSITA’ Vv/VT

= crosslinking monomers IMPRINTED GELS MOLECULAR IMPRINTING COMPLEX FORMATION I I = initiator = template = functional monomers = crosslinking monomers CROSSLINKING WASHING

IMPRINTED POLYMERIC GELS: CHARACTERISTICS Binding affinity: a measure of how well the template molecule is attracted to the binding site Selectivity : the ability to differentiate between the template and other molecules Binding capacity : the maximum amount of template bound per mass or volume of polymer

BINDING AFFINITY Macromolecular sites concentration Template concentration Forward reaction (binding) Backward reaction (un-binding) Association constant

SELECTIVITY a = Ka1/Ka2 1 ≤ a ≤ 8

EXAMPLE : SWELLING CONTROL NETWORK SWELLING: DRUG CAN BE RELEASED P A = DRUG A =ANALYTE = PROTEIN

EXAMPLE 2: TARGETED DELIVERY CELLULAR RECEPTOR TISSUES OR CELLULAR LINING IMPRINTED FILM DRUG HYDROGEL R

BIBLIOGRAFIA Lapasin R, Pricl S, Rheology of Industrial Polysaccharides; Theory and Applications, Chapman and Hall, London, 1995. Coviello T, Grassi M, Rambone G, Santucci E, a Carafa M , Murtas E, Riccieri F M, Franco Alhaique F. Novel hydrogel system from scleroglucan: synthesis and characterization J. Contr. Rel. 60, 367–378, 1999. A. Kydonieus (Ed.), Treatise on Controlled Drug Delivery, Marcel Dekker, New York, 1992, pp. 54-55. Colombo, P. 1993. Swelling-controlled release in hydrogel matrices for oral route. Adv. Drug. Dev. Rev., 11, 37 – 57 Grassi M, Colombo I, Lapasin R. Drug release from an ensemble of swellable crosslinked polymer particles. J. Contr. Rel. 68, 97-113, 2000.