The need for speciality polymers for drug delivery applications led us to investigate the use of well-defined narrow-dispersed methacrylate-based polymers in this work, exploring their potential in pharmaceutical formulations for drug encapsulation, site-specific release, and the formation of amorphous solid dispersions (ASDs).
A library of methacrylate-based polymers including poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMA) and poly(methacrylic acid) (PMAA), as well as copolymers composed of PPEGMA and poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA), were first synthesised using reversible addition- fragmentation chain transfer (RAFT) polymerisation. The synthesis was optimised, and a high degree of control in the polymerisation process was confirmed by the reproducible synthesis of polymers and copolymers with targeted molecular weights and low polydispersity.
Nano-sized monodispersed polyelectrolyte complex (PEC) nanoparticles were next prepared via self-assembly of oppositely charged polymers, PDMAEMA and PMAA. The PECs did not entrap hydrophobic drugs (paclitaxel or dexamethasone) efficiently. Hydrophilic drugs including gemcitabine, 5- fluorouracil, and carmofur, on the other hand, were efficiently loaded into the nanoparticles. However, as anticipated, their release from the PECs was very rapid in media at physiological pH and mildly acidic pH.
Methacrylic acid polymers with DPs of 80 and 20 were able to produce ASDs
of lidocaine, a poorly water-soluble drug, after ball milling. These form as a result of the interactions between the acidic polymer and the basic drug. X-ray diffraction and differential scanning calorimetry analysis confirmed that the ASDs maintained their amorphous nature and were stable under accelerated storage conditions (40 °C and 75% RH) over 9 months. Dissolution studies revealed that the presence of the acidic polymer in the formulation and the amorphous nature of the formulation (lack of crystal lattice) removed the energy barrier to dissolution, lowered the microenvironment pH, and resulted in an increase in the dissolution rate and solubility of the drug.