Poly(methacrylic acid) hydrogels crosslinked by poly(ethylene glycol) diacrylate as pH-responsive systems for drug delivery applications
Hidrogelovi na bazi poli(metakrilne kiseline) umreženi korišćenjem poli(etilen-glikol) diakrilata, kao pH-osetljivi nosači za kontrolisano otpuštanje lekova
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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 - o...xaprozin 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 – oksaprozi...na 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.
Keywords:
smart materials / colon-specific delivery / ciprofloxacin / oxaprozin / Pametni materijali / kolon-ciljano otpuštanje lekova / ciprofloksacin / oksaprozinSource:
Hemijska industrija, 2023, 77, 4, 235-249Publisher:
- Savez hemijskih inženjera Srbije
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200287 (Innovation Center of the Faculty of Technology and Metallurgy) (RS-MESTD-inst-2020-200287)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200135 (University of Belgrade, Faculty of Technology and Metallurgy) (RS-MESTD-inst-2020-200135)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200026 (University of Belgrade, Institute of Chemistry, Technology and Metallurgy - IChTM) (RS-MESTD-inst-2020-200026)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200178 (University of Belgrade, Faculty of Biology) (RS-MESTD-inst-2020-200178)
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Inovacioni centarTY - JOUR AU - Ugrinović, Vukašin AU - Marković, Maja AU - Božić, Bojan AU - Panić, Vesna AU - Veljović, Đorđe PY - 2023 UR - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/6852 AB - 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. AB - 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. PB - Savez hemijskih inženjera Srbije T2 - Hemijska industrija T1 - Poly(methacrylic acid) hydrogels crosslinked by poly(ethylene glycol) diacrylate as pH-responsive systems for drug delivery applications T1 - Hidrogelovi na bazi poli(metakrilne kiseline) umreženi korišćenjem poli(etilen-glikol) diakrilata, kao pH-osetljivi nosači za kontrolisano otpuštanje lekova EP - 249 IS - 4 SP - 235 VL - 77 DO - 10.2298/HEMIND221228018U ER -
@article{ author = "Ugrinović, Vukašin and Marković, Maja and Božić, Bojan and Panić, Vesna and Veljović, Đorđe", year = "2023", 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.", publisher = "Savez hemijskih inženjera Srbije", journal = "Hemijska industrija", title = "Poly(methacrylic acid) hydrogels crosslinked by poly(ethylene glycol) diacrylate as pH-responsive systems for drug delivery applications, Hidrogelovi na bazi poli(metakrilne kiseline) umreženi korišćenjem poli(etilen-glikol) diakrilata, kao pH-osetljivi nosači za kontrolisano otpuštanje lekova", pages = "249-235", number = "4", volume = "77", doi = "10.2298/HEMIND221228018U" }
Ugrinović, V., Marković, M., Božić, B., Panić, V.,& Veljović, Đ.. (2023). Poly(methacrylic acid) hydrogels crosslinked by poly(ethylene glycol) diacrylate as pH-responsive systems for drug delivery applications. in Hemijska industrija Savez hemijskih inženjera Srbije., 77(4), 235-249. https://doi.org/10.2298/HEMIND221228018U
Ugrinović V, Marković M, Božić B, Panić V, Veljović Đ. Poly(methacrylic acid) hydrogels crosslinked by poly(ethylene glycol) diacrylate as pH-responsive systems for drug delivery applications. in Hemijska industrija. 2023;77(4):235-249. doi:10.2298/HEMIND221228018U .
Ugrinović, Vukašin, Marković, Maja, Božić, Bojan, Panić, Vesna, Veljović, Đorđe, "Poly(methacrylic acid) hydrogels crosslinked by poly(ethylene glycol) diacrylate as pH-responsive systems for drug delivery applications" in Hemijska industrija, 77, no. 4 (2023):235-249, https://doi.org/10.2298/HEMIND221228018U . .