Hydrogels based on poly(styrene-co-maleic anhydride) for the application of reversible male contraceptive

Verwey, Lehani (2016-03)

Thesis (MSc)--Stellenbosch University, 2016.

Thesis

ENGLISH ABSTRACT: The use of a polymeric gel as male contraceptive, injected into the vas deferens of the male, has attracted a considerable amount of interest due to improved criteria over the current available options. The non-invasive character of these gels offer reduced side effects and improved reversibility over a vasectomy, rendering a promising new alternative to satisfy society’s ever increasing demand for an ideal contraceptive. This thesis focuses on the design, synthesis and characterisation of a polymer hydrogel system with improved biocompatibility and reversibility properties for contraception purposes in the male. Poly(styrene-co-maleic anhydride) (SMA), a biocompatible, commercially available copolymer that easily undergoes chemical modification through its highly reactive maleic anhydride residues is a candidate system for use in these hydrogel matrices. RAFT (reversible addition fragmentation chain transfer) mediated polymerisation was utilised for the synthesis of well-defined SMA, followed by two post-polymerisation modification approaches. The first, prepared through modification of the anhydride residues in the SMA backbone and the alternative, through chain end modification of the thiocarbonyl thio group of the RAFT-made SMA. Preference was given to the first approach during the present study, as side-reactions turned out to hamper the disulphide formation of thiol terminal-SMA. Water-soluble boronic acid functionalised polymers (SMI-BA) were prepared by partial modification of the reactive maleic anhydride residues in SMA with 3-aminophenylboronic acid (BA). SMI-BA was combined with poly(vinyl alcohol) (PVA) to prepare the required hydrogels. Gelation is achieved within minutes after mixing of aqueous solutions of SMI-BA and PVA, based on reversible ester crosslink formation between the boronic acid groups in SMI-BA and the 1,3 diols in PVA. The structural properties of the gels were characterized by oscillatory rheometry as a function of composition and degree of modification (SMI-BA). Adequate gelation times of approximately 1-5 minutes (37 C, PBS, pH = 7.4), with storage moduli (G’) of 12 kPa – 50 kPa were obtained. Rapid reversibility of the gels is achieved within a few minutes by the addition of glucose in combination with sodium bicarbonate (NaHCO3). The results indicate that the polymeric hydrogel is a promising candidate for further investigation as an injectable gel for male contraception purposes.

AFRIKAANSE OPSOMMING: Die gebruik van 'n polimeriese jel as manlike voorbehoedmiddel deur inspuiting in die vas deferens buis van die man het aansienlike belangstelling gelok as gevolg van verbeterde kriteria oor huidige beskikbare opsies. Die nie-indringende karakter van hierdie jels bied verminderde newe-effekte en verbeterde omkeerbaarheid oor 'n vasektomie, wat as belowende nuwe alternatief kan dien vir die samelewing se toenemende vraag na 'n ideale voorbehoedmiddel. Hierdie tesis fokus op die ontwerp, sintese en karakterisering van 'n polimeer jel sisteem met verbeterde biologiese geskiktheid en omkeerbaarheid vir voorbehoeding doeleindes in die manlike geslag. Poli(stireen-ko-maleïne anhidried) (SMA), 'n kommersieel beskikbare kopolimeer wat maklik chemiese modifikasie ondergaan deur middel van sy hoogs reaktiewe maleïne anhidried groepe dien as goeie kandidaat vir hierdie jel matriks doeleindes. RAFT bemiddelde polimerisasie is aangewend vir die sintese van goed gedefinieerde SMA, gevolg deur twee sekondere polimerisasie benaderings. Die eerste, voorberei deur modifikasie van die anhidried groepe in die SMA ruggraat en die alternatief deur modifikasie van die tiokarboniel tio groep van die SMA polimeer. Voorkeur is gegee aan die eerste benadering tydens die huidige studie, as gevolg van newe-reaksies wat die disulfied formasie belemmer na die sintese van tiol terminale SMA. Water-oplosbare boroniese suur getransformeerde polimere (SMI-BA) is voorberei deur die gedeeltelike modifikasie van die reaktiewe maleïne anhidried reste in SMA met 3-amienfenielboroniese suur (BA). SMI-BA is gekombineer met poli(vinielalkohol) (PVA) om die vereiste jels te vorm. Jel formasie is binne minute na die toevoeging van water oplosbare SMI-BA en PVA bereik. Netwerk formasie is gebaseer op omkeerbare ester binding formasie tussen die suur groepe in SMI-BA en die 1,3 diol in PVA. Die strukturele eienskappe van die jels is gekenmerk deur ossillasie reologie as 'n funksie van samestelling en graad van verandering (SMI-BA). Voldoende jel formasie van ongeveer 1-5 minute (37 C, PBS, pH = 7.4), met die stoor modulis (G') van 12 kPa - 50 kPa is verkry. Vinnige, voldoende omkeerbaarheid van die jels is binne 'n paar minute bereik deur die byvoeging van glukose in kombinasie met natriumbikarbonaat (NaHCO3). Die resultate dui daarop dat die polimeriese jel sisteem dien as belowende kandidaat vir verdere ondersoek as 'n inspuitbare jel vir manlike voorbehoeding doeleindes.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/98310
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