Preparation Of Copolymers With Multi-components And Multi-blocks And Their Application In Sustained Release

In order to facilitate the taking of medicines and reduce side effects of medicines,sustained release of medicines has been a research focus of pharmaceutical preparations.Macromolecules can be embedded and loaded with drug molecules through covalent bonds,electrostatic interactions,hydrogen bonding and chain entanglement,which is the first choice for drug carriers.Compared with natural polymers and existing simple polymers,the designability of composition and segment structure for copolymers,it is convenient to introduce specific functional groups for drug molecular structure and adjust polymer chain conformation to optimize drug loading and sustained release behavior.Reversible addition-fragmentation chain transfer radical(RAFT)living polymerization has the characteristics of mild conditions and wide range of applicable monomers,and is particularly suitable for preparing multi-component block copolymers(Multi-BCPs).In this paper,miniemulsion RAFT polymerization is used to study homopolymerization kinetics of four monomers and effects of ratio for monomer,chain transfer agent and initiator on copolymerization product and chain composition.Furthermore,multi-block copolymers(Multi-BCPs)with precise segment composition are prepared.Finally,loading and sustained release behaviors of Multi-BCPs on fluorescein sodium(FS)are discussed.In order to determine the appropriate polymerization time,hydrophilic monomers 4-vinylpyridine(4VP),hydroxyethyl acrylate(2HA)and hydrophobic monomers styrene(St)and t-butyl acrylate(t BA)are selected for study object,explored the ability of 2-(dodecyltrithiocarbonate)-2-methylpropionic acid(DDMAT)to regulate four monomers.The results show that 4VP,St and 2HA at 8 h,t BA at 6 h can obtain stable number average molecular weight(Mn)and narrow molecular weight distribution(PDI)polymers.A series of tetrablock copolymers(4-BCPs)are synthesized by changing the sequence of monomer and ratio of monomer,DDMAT and azodiisobutyronitrile(AIBN),the effect of ratio change on polymerization activity and segment length is studied.Results show that the order of adding four monomers will not affect polymerization process;increasing ratio of DDMAT to AIBN can significantly reduce PDI of copolymers;increasing ratio of monomer to DDMAT can make polymer chain more regular while increasing the length of segment.Based on polymerization conditions of 4-BCPs,twenty block copolymers(20-BCPs)and twelve block copolymers(12-BCPs)are synthesized.Results show that synthesized 12-BCPs have precise segment structure,and monomer composition ratio is nearly 1: 1: 1: 1.The monodisperse size of copolymers is analyzed by dynamic light scattering(DLS).Results show that the self-assembly size of block copolymer is affected by structure of segment sequence.The more hydrophilic of end block,the larger the self-assembly size.Using 12-BCPs with clear structure as carriers,the effects of copolymers on initial loading and sustained release behavior of FS are studied.The results showed that five groups of copolymers all showed large initial loading(49.6-74.6 mg/g)and long sustained release time(18-30 day).The copolymer P(2HA-St-4VP-t BA)has the largest self-assembly volume(13.40 ?m),the largest drug loading capacity(74.6 mg/g),the most stable release state and the longest sustained release time(30 day).The strength of chain entanglement caused by difference in sequence structure will affect loading and sustained release behavior of carrier.The larger the self-assembly size of copolymers,the more loading amount of FS.When chain end of polymers has a functional group that can form a hydrogen bond with FS,sustained release time of copolymers will be extended.Driving force for sustained release is concentration difference between sustained release solution and copolymers.