6 research outputs found
Co-initiated hyperbranched-polydendron building blocks for the direct nanoprecipitation of dendron-directed patchy particles with heterogeneous surface functionality
Direct synthesis of nanoparticles with spatial heterogeneity for tailored cellular interactions
Model studies of the sequential and simultaneous statistical modification of dendritic functional groups and their implications within complex polymer architecture synthesis
Accurate analysis of model systems by MALDI-TOF has established the diversity of structures formed during post-synthesis functionalisation of complex polymer architectures. NMR studies alone are shown to be highly misleading.</p
Designing single trigger/dual-response release and degradation into amine-functional hyperbranched-polydendron nanoprecipitates
The synthesis of complex polymer architectures using relatively facile experimental protocols provides access to materials with the opportunity to control functionality and physical behaviour. The scope of hyperbranched-polydendron chemistries has been expanded here to include primary chains comprising amine-functional ‘homopolymer’, ‘statistical copolymer’ and amphiphilic ‘block copolymer’ analogues using 2-(diethyl amino)ethyl methacrylate, 2-hydroxy propyl methacrylate and t-butyl methacrylate. The different primary chain chemistry and architectures leads to a marked variation in nanoprecipitation behaviour and the response of the resulting amine-functional nanoparticles to varying pH. When acid-sensitive and acid-stable branchers, 1,4-butanediol di(methacryoyloxy)-ethyl ether and ethylene glycol dimethacrylate respectively, are utilised, nanoparticles with encapsulation properties are formed and may be triggered to either release-and-disassemble or release-disassemble-degrade to form a solution of lower molecular weight constituent primary chains
Linear and branched polymer prodrugs of the water-soluble nucleoside reverse-transcriptase inhibitor emtricitabine as structural materials for long-acting implants
Long-acting drug delivery is a growing area of interest as it overcomes many challenges related to patient adherence to therapy and the pill burden associated with chronic illness. Injectable formulations are becoming more common and drug-releasing implants also provide several opportunities. Highly water soluble drug compounds are poor candidates for long-acting delivery. Here, the water-soluble nucleoside reverse transcriptase inhibitor emtricitabine (FTC) has been used as a novel A–B monomer in step-growth polymerisation with chloroformate functional C(n) monomers, to produce new poly(carbamate/carbonate) structures with varying architecture. The polymer prodrugs were all solid at ambient temperature and have been shown to release FTC when subjected to mixed gender human plasma. Vacuum compression moulding has been used to form solid rod implants without polymer degradation; the rods show FTC release over long periods in the presence of microsomes, establishing the basis of a polymer prodrug strategy for FTC delivery
Polymer-prodrug conjugates as candidates for degradable, long-acting implants, releasing the water-soluble nucleoside reverse-transcriptase inhibitor emtricitabine
Circulating, soluble polymer-drug conjugates have been utilised for many years to aid the delivery of sensitive, poorly-soluble or cytotoxic drugs, prolong circulation times or minimise side effects. Long-acting therapeutics are increasing in their healthcare importance, with intramuscular and subcutaneous administration of liquid formulations being most common. Degradable implants also offer opportunities and the use of polymer-prodrug conjugates as implant materials has not been widely reported in this context. Here, the potential for polymer-prodrug conjugates of the water soluble nucleoside reverse transciption inhibitor emtricitabine (FTC) is studied. A novel diol monomer scaffold, allowing variation of prodrug substitution, has been used to form polyesters and polycarbonates by step-growth polymerisation. Materials have been screened for physical properties that enable implant formation, studied for drug release to provide mechanistic insights, and tunable prolonged release of FTC has been demonstrated over a period of at least two weeks under relevant physiological conditions