Poly(methacrylic acid) hydrogels crosslinked by poly(ethylene glycol) diacrylate as pH-responsive systems for drug delivery applications

Abstract

Hydrogels are attractive materials for drug delivery applications due to biocompatible, porous structure with the possibility to load and deliver drugs in a controllable manner. In this paper, poly(methacrylic acid) (PMAA) hydrogels are described, which are synthesized by free-radical polymerization, using poly(ethylene glycol) diacrylate (PEGDA) as a crosslinker. Influence of the PEGDA content on hydrogel properties was investigated and compared to commonly used crosslinker - N,N’-methylenebisacrylamide (MBA). The increasing concentration of crosslinkers led to a higher degree of crosslinking, which was demonstrated by a higher degree of conversion, lower swelling capacity, and improved thermal stability and mechanical properties. Also, the PEGDA-crosslinked hydrogels demonstrated a higher degree of crosslinking than the corresponding MBA-crosslinked hydrogels. Potential application of the synthesized hydrogels for controlled drug delivery was investigated by using two model drugs - oxaprozin and ciprofloxacin. In vitro drug release tests indicated that the interactions between drug, polymer and medium have a key influence on the drug release behavior, rather than the swelling rate. Drug release tests in simulated gastrointestinal conditions indicated that PEGDA-crosslinked PMAA hydrogels are suitable for colon-targeted delivery of oxaprozin.

Zbog svoje biokompatibilne, visoko-porozne strukture i mogućnosti da nose i kontrolisano otpuštaju lekove, hidrogelovi su našli široku primenu u biomedicini. U ovom radu, hidrogelovi na bazi poli(metakrilne kiseline) (PMK), umreženi pomoću poli(etilen-glikol) diakrilata (PEGDA), sintetisani su metodom toplotno-indukovane slobodno-radikalske polimerizacije. Ispitan je uticaj sadržaja PEGDA na svojstva hidrogelova i upoređen sa uticajem najčešće korišćenog umreživača – N,N' – metilenbisakrilamida (MBA). Povećanje količine oba umreživača dovelo je do većeg stepena umreženja, što je bilo manifestovano povećanjem stepena konverzije monomera, smanjenjem ravnotežnog stepena bubrenja i poboljšanim toplotnim i mehaničkim svojstvima. Takođe, hidrogelovi umreženi pomoću PEGDA pokazali su veći stepen umreženja u odnosu na odgovarajuće hidrogelove umrežene pomoću MBA. Mogućnost primene dobijenih hidrogelova za kontrolisano otpuštanje lekova, ispitivano je korišćenjem dva leka – oksaprozina i ciprofloksacina. In vitro testovi otpuštanja pokazali su da presudan uticaj na kinetiku otpuštanja imaju međusobne interakcije između leka, hidrogela i medijuma, a ne stepen i brzina bubrenja hidrogela. Prema tome, otpuštanje ciprofloksacina je bilo intenzivnije u kiseloj sredini, a oksaprozina u baznoj. Otpuštanje u simuliranim gastrointestinalnim uslovima pokazalo je da su PEGDA-umreženi hidrogelovi pogodni za kontrolisano otpuštanje oksaprozina u debelo crevo.