pH sensitive polymer systems can be utilized as smart nanocarriers to deliver hydrophobic drugs specifically to solid tumors or to acidosis-affected rheumatic joints. In this study, a poly(L-aspartic acid-graftimidazole)-block-poly(ethylene glycol) (P(Asp-g-Im)-PEG) block copolymer was synthesized as a pH sensitive nanocarrier targeting acidic pH environments. The polypeptide P(Asp), which was used as a backbone for the hydrophobic block, was synthesized by ring opening polymerization with N-carboxylanhydride (NCA) of β-benzyl-aspartic acid. PEG was included as the hydrophilic block and the polymer was functionalized with imidazole groups to confer pH sensitivity. The prepared P(Asp-g-Im)-PEG is zwitterionic with a pI 6.5; 60% of the available carboxyl groups of P(Asp)-PEG were substituted by imidazole groups. Furthermore, the potentiometric titration curve of P(Asp-g-Im)-PEG demonstrated a broad buffer zone. The micelles prepared from P(Asp-g-Im)-PEG showed pH dependent critical micelle concentrations (CMC), particle sizes, zeta potentials, and morphologies.

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While the number and diversity of lead compounds has increased with the development of science technologies, ca. 90 % of new chemical entities under development have shown low aqueous solubility, classified as class II or IV of the biopharmaceutics classification system (BCS). The low aqueous solubility hinders their clinical translations due to low bioavailability and dissolution-limited absorption of orally-administered drugs. Several technologies have been employed to improve the solubility of poorly water-soluble drugs. In this paper, a new method of nanoparticulation using fat and a supercritical fluid (NUFS) for the formulation of hydrophobic drugs was applied to solve the low solubility problem. A typical BCS class II drug, itraconazole, was selected and formulated with hydroxypropyl methylcellulose, emulsification, and anticoagulating agents for NUFS. The non-spherical itraconazole nanoparticles prepared by NUFS were ~300-500 nm in size with a ~15-fold improved dissolution rate compared to non-nanoparticles of itraconazole (i.e., raw itraconazole). In addition, a high drug content of ~46 % by weight and a drug loading efficiency greater than 85 % were achieved. Therefore, the new technology for nano-platforms could be a promising solution for solubilization of poorly water-soluble drugs, resulting in improved bioavailability.