Synthesis of E-caprolactone based antimicrobial biodegradable scaffolds

Thesis (MSc)--Stellenbosch University, 2019.ENGLISH ABSTRACT: Antimicrobial and biodegradable fibers are essential in medical applications, especially those in direct contact with the skin like wound dressings. It is ideal to have wound dressings that can eliminate microbes from the wound bed and be biodegradable. The use of biocompatible and biodegradable polymers in production of wound dressings will lead to a novel approach. Some biodegradable and biocompatible polymers such as polycaprolactone, poly (lactic acid), poly (lactic-co-glycolic acid) have been approved by the Food and Drug Administration for wound dressings, tissue engineering, drug delivery, etc. In this study, polycaprolactone was synthesized and antimicrobial agents were attached to the polymer backbone. The polymerization of caprolactone was first optimized via ring opening polymerization using tin(II) 2-ethylhexanoate (Sn(Oct2)) or Candida antarctica lipase. After the optimization, poly(ε-caprolactone-co-γ-amino-ε-caprolactone) (poly(CL-co-ACL)) was successfully synthesized. This was achieved in three steps: synthesis of γ-(carbamic acid benzyl ester)-ε-caprolactone (γ-CABεCL); copolymerisation of the γ-CABεCL and ε-caprolactone, via ring-opening polymerization (ROP) using Sn(Oct2) as a catalyst and water as initiator; and finally, deprotection via acidolysis. The structures of the monomers and polymers/copolymers were confirmed by 1H-NMR, 13C-NMR, and ATR-FTIR spectroscopy. The molecular weight and molar mass dispersity of the polymer was determined using GPC. To induce antimicrobial properties to poly(CL-co-ACL), it was modified by grafting polylysine or quaternization of the pendant amine functional groups. Caprolactone-based scaffolds were fabricated by electrospinning and they were characterized by SEM. The antimicrobial nanofibers were further characterized by zone inhibition assay. The polymers showed antimicrobial activity against both Staphylococcus aureus and Pseudomonas aeruginosa after 24 h of incubation. Biodegradation studies were carried out using Pseudomonas lipase at 37 °C and nanofibers degraded within 4 days.AFRIKAANSE OPSOMMING: Antimikrobiese en bio-afbreekbare vesels is noodsaaklik vir mediese toepassings, veral daardie wat in direkte kontak kom met die menslike vel soos byvoorbeeld wondbedekkings. Dit is ideaal om wondbedekkings te hê wat bio-afbreekbaar is en instaat daartoe is om mikrobes te elimineer van die wond. Die gebruik van bio-verenigbare en bio-afbreekbare polimere in die produksie van wondbeddekkings kan lei tot ‘n innoverende benadering. Sommige bio-afbreekbare en bio-verenigbare polimere soos byvoorbeeld polikaprolaktoon, poli(laktiessuur), poli(lakties-ko-glukolsuur) is goedgekeur deur die Food and Drug Administration vir die gebruik in wondbedekkings, weefselgeniëring, medisyne toediening, ens. In hierdie studie was polikaprolaktoon gesintetiseer en antimikrobiese stowwe aan die polimeer ruggraat geheg. Die polimerisasie van kaprolaktoon was aanvanklik geoptimeer deur middel van ring-openingspolimerisasie met die gebruik van tin(II) 2-etielheksanoaat (Sn(Oct2)) of Candida antarctica lipase. Na die optimalisering, was poli(ε-kaprolaktoon-ko-γ-amino-ε-kaprolaktoon) (poli(KL-ko-AKL)) suksesvol gesintetiseer. Dit was in drie stappe uitgevoer: sintese van γ-(karbamiese suur bensiel ester)-ε-kaprolaktoon (γ-KABεKL); kopolymerisasie van die γ-KABεKL en ε-kaprolaktoon deur middle van ring-openingspolimerisasie (ROP) wat gebruik te maak van Sn(Oct2) as katalis en water as inisiator; en uiteindelik, die ontbeskerming deur middle van suurlisering. Die strukture van die monomere en polimere/kopolimere was bevestig deur 1H-KMR, 13C-KMR, en ATR-FTIR spektroskopie. Die molekulêre massa en molêre massa dispersie van die polimeer was bepaal deur GPC. Om die antimikrobiese eienskappe by poli(KL-ko-AKL) te voeg, was dit gemodifiseer deur die entings polimerisasie van polilisiene of kwaternarisering van die aanhangende amien funksionele groepe. Steiers gebaseer op kaprolaktoon was deur die elekrospin proses vervaardig en deur SEM gekarakteriseer. Die antimikrobiese nanovesels was verder deur sone inhibisie toetse gekarakteriseer. Die polimere het antimikrobiese aktiwiteit teen beide Staphylococcus aureus en Pseudomonas aeruginosa na inkubasie van 24 h getoon. Bio-afbreekbare studies is uitgevoer op Pseudomonas lipase teen 37 °C en die nanovesels het na 4 dae afgebreek.Master