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The aim of this paper is to propose equations for the diffusion of drugs for investigated drug/hydrogel systems using the parameters affecting the transport of drug through poly- (2-hydroxyethylmethacrylate/itaconic acid) (P(HEMA/IA)), poly(2-hydroxyethylacrylate/ita- conic acid) (P(HEA/IA)), and poly(2-hydroxyethylmethacrylate/poly(alkyleneglycol) (meth)- acrylates) (P(HEMA/BIS)) copolymeric hydrogels. Different monomer types, as well as the variable content of some components in hydrogel composition (the amount of ionizable comonomer (IA) and different type of nonionic poly(alkyleneglycol) (meth)acrylates), ultimately defined the pore size available for drug diffusion. The hydrogels synthesized ranged from nonporous to microporous, based on the classification in accordance to the pore size, and could be classified as hydrogels that contain ionic groups and hydrogels without ionic groups. The drugs selected for this study are bronchodilators-theophylline (TPH), fenethylline hydrochloride (FE), and antibiotic cephalexin (CEX). Results of in vitro drug release tests defined the release systems based on the drug type, as well as the type of hydrogel used. The diffusion coefficient of drugs and the restriction coefficient, λ, defined as the ratio of solute to 'pore' radius (rs/rζ) that describes the ease of drug release from the gels, were used as factors that govern the release process., Cilj ove studije je da se predlože difuzione jednačine za ispitivane sisteme lek/hidrogel. Korišćeni su hidrogelovi poli(2-hidroksietilmetakrilat/itakonska kiselina) (P(HEMA/IK)), poli(2-hidroksietilakrilat/itakonska kiselina) (P(HEA/IK)) i poli-(2-hidroksietilmetakrilat/poli(alkilenglikol)-(met)akrilati) (P(HEMA/BIS)). Komponenta koja se menja u sastavu hidrogela HEMA, HEA, kao i udeo komponente sa promenljivim sadržajem (udeo jonizujućeg komonomera (IK) i tip BIS komponente) definiše veličinu pora koja je dostupna za difuziju leka. U ovoj studiji su korišćeni lekovi bronhodilatori teofilin (TPH) i fenetilin-hidrohlorid (FE), i antibiotik cefaleksin (CEX). Ovi gelovi su klasifikovani u režimu poroznosti kao neporozni i mikroporozni, sa veličinom pora u opsegu 0,18-24,9 nm. Kontrolisano otpuštanje lekova je izvedeno u in vitro uslovima u puferu pH 7,40 i na 37 °C, da bi se odredili difuzioni koeficijenti leka u hidrogelovima. Na osnovu toga su predložene jednačine difuzije leka kroz hidrogel za svaki sistem lek/hidrogel. Rezultati dobijeni fitovanjem eksperimentalnih podataka su pokazali da difuzija leka zavisi od hemijske strukture i morfologije hidrogela i parametra λ, koji predstavlja odnos prečnika leka i veličine pora. Eksponencijalna zavisnost koeficijenta restrikcije od normalizovanog koeficijenta difuzije je dobijena za sisteme TPH/P(HEMA/IA), FE/P(HEMA/ /IA), CEX/P(HEMA/BIS) i CEX/P(HEA/IA).Utvrđeno je da veliki uticaj na difuziju leka imaju interakcije koje se odigravaju između funkcionalnih grupa leka i polimerne mreže.

New types of hydrogels were prepared by the radical copolymerization of 2-hydroxyethyl methacrylate, itaconic acid and four different poly(alkylene glycol) (meth)acrylate components (Bisomers) in a water/ethanol mixture as solvent. The polymers swell in water at 25°C to yield homogeneous transparent hydrogels. All the hydrogels displayed pH sensitive behavior in buffers of the pH range from 2.20 to 7.40, under conditions similar to those of biological fluids. The presence of these two comonomers, which were added to HEMA, increased the swelling degree of the hydrogels and gave gels with better elasticity. The hydrogels were thermally stable in the vicinity of the physiological temperature (37°C). The copolymer containing pure poly(ethylene glycol) acrylate units generally had the best properties. The tests performed on the hydrogels confirmed that they were neither hemolytic nor cytotoxic. The copolymer samples showed better cell viability and less hemolytic activity than the PHEMA sample, confirming the assumption that poly(alkylene glycols) improve the biocompatibility of hydrogels. Due to their swelling and mechanical characteristics, as well as the very good biocompatibility and bioadhesive properties, poly(Bisomer/HEMA/IA) hydrogels are promising for utilization in the field of biomedicals, especially for the controlled release of drugs., Radikalnom kopolimerizacijom 2-hidroksietil metakrilata (HEMA), itakonske kiseline (IK) i četiri tipa poli(alkilen glikol) (met)akrilata (Bisomera-BIS) dobijeni su novi poli(BIS/HEMA/IK) hidrogelovi, u smeši voda/etanol kao rastvaraču. Ispitan je uticaj tipa Bisomera na bubrenje u puferima pH 2,20-7,40, u uslovima sličnim biološkim fluidima. Takođe, praćenje i uticaj na mehanička svojstva, morfologiju i termičko ponašanje dobijenih gelova. Testiranje biokompatibilnosti in vitro napoli (BIS/HEMA/IK) hidrogelovima pokazuje da nema ćelijske toksičnosti, niti hemolitičke aktivnosti. Gelovi poseduju zadovoljavajuću bioadhezivnost.

Radikalnom kopolimerizacijom 2-hidroksietil metakrilata (HEMA), itakonske kiseline (IK) i četiri tipa poli(alkilen glikol) (met)akrilata (Bisomera-BIS) dobijeni su novi poli(BIS/HEMA/IK) hidrogelovi, u smeši voda/etanol kao rastvaraču. Ispitan je uticaj tipa Bisomera na bubrenje u puferima pH 2,20-7,40, u uslovima sličnim biološkim fluidima. Takođe, praćen je i uticaj na mehanička svojstva, morfologiju i termičko ponašanje dobijenih gelova. Testiranje biokompatibilnosti in vitro na poli (BIS/HEMA/IK) hidrogelovima pokazuje da nema ćelijske sličnosti, niti hemlitičke aktivnosti. Gelovi poseduju zadovoljavajuću bioadhezivnost., New types of hydrogels were prepared by the radical copolymerization of 2-hydroxyethyl methacrylate, itaconic acid and four different poly(alkylene glycol) (meth)acrylate components (Bisomers) in a water/ethanol mixture as solvent. The polymers swell in water at 25 degrees C to yield homogeneous transparent hydrogels. All the hydrogels displayed pH sensitive behavior in buffers of the pH range from 2.20 to 7.40, under conditions similar to those of biological fluids. The presence of these two comonomers, which were added to HEMA, increased the swelling degree of the hydrogels and gave gels with better elasticity. The hydrogels were thermally stable in the vicinity of the physiological temperature (37 degrees C). The copolymer containing pure poly(ethylene glycol) acrylate units generally had the best properties. The tests performed on the hydrogels confirmed that they were neither hernolytic nor cytotoxic. The copolymer samples showed better cell viability and less hemolytic activity than the PHEMA sample, confirming the assumption that poly(alkylene glycols) improve the biocompatibility of hydrogels. Due to their swelling and mechanical characteristics, as well as the very good biocompatibility and bioadhesive properties, poly(Bisomer/HEMA/IA) hydrogels are promising for utilization in the field of biomedicals, especially for the controlled release of drugs.

Novel poly(Bisomer/HEMA/IA) hydrogels were prepared by radical copolymerization of poly(alkylene glycol) (meth)acrylates, i.e. short chains Bisomers, 2-hydroxyethyl methacrylate (HEMA) and itaconic acid (IA) in a mixture of water/ethanol as solvent. These hydrogels were characterized in terms of swelling in conditions similar to the biological fluids (pH range 2.20-7.40 buffer solutions), compression-strain measurements, thermal properties and morphology. The influence of the type of Bisomer and of the itaconic acid on swelling and mechanical properties, as well as on morphology and thermal behavior of the resulting hydrogels, were investigated. The in vitro study of biocompatibility, carried out with the hydrogels containing different types of Bisomers, showed no evidence of cell toxicity nor any considerable hemolytic activity. All hydrogels showed satisfactory bioadhesive properties, so these materials have potential as drug carriers or biological glue and sealants.