Introduction The prolonged administration of drugs for long term conditions faces the issue of poor patient compliance when frequent repeated administration of drug is required, e.g. a daily oral dose. Pre-formed sustained release implants overcome this issue but require invasive surgery. In situ-forming implants (ISFI) are easier to administer, allow site specific delivery and offer ease of manufacture. However, ISFIs suffer from issues such as high burst release of drug, toxicity and stability of the system. Hence there is a need for an ISFI capable of sustained drug release whilst avoiding the current drawbacks of ISFI systems. We have developed a nanocomposite ISFI based on nanogels and solid drug nanoparticles, this system forms an aggregate drug depot in response to the dual triggers of salt and temperature, Fig 1. The combination of these dual triggers removes the colloidal stability of the nanogel allowing aggregation to occur, whilst simultaneously entrapping &gt; 95% of the drug payload. Results Two poly(N-isopropylacrylamide) (PNIPAM) and poly(NIPAM-co-allylamine) nanogel samples were produced by precipitation polymerization. The nanogels aggregated in phosphate buffered saline when heated above 32 °C. When mixed with solid drug nanoparticles the nanocomposites provided long term sustained release of drug, with a tuneable release rate depending on the formulation of drug and the polymer composition of the nanogels species used in the composite. The polymer composition gave ISFIs with different porosity. The system is also injectable through a 20G hypodermic needle. Conclusions We have created an injectable drug delivery depot, which allows the rate of drug release to be tuned, minimises burst release, and shows minimal cytotoxicity. The system is able to give long term sustained drug release of over 120 days. This nanocomposite ISFI is an attractive candidate for the sustained delivery of poorly water soluble drugs with high potency.

Dual-stimuli responsive injectable nanogel/solid drug nanoparticle nanocomposites for release of poorly soluble drugs

254th National Meeting (2017)

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