Pharmacokinetic and biodistribution studies of N-(2-hydroxypropyl)methacrylamide copolymer-dexamethasone conjugates in adjuvant-induced arthritis rat model.

N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymer has been found to be arthrotropic (joint-targeting) in the adjuvant-induced arthritis (AA) rat model using magnetic resonance imaging (MRI). In this manuscript, we report the quantitative pharmacokinetics and biodistribution (PK/BD) of 125I-labeled HPMA copolymer−dexamethasone conjugate (P−Dex) in AA rats. Structural parameters of the prodrug such as the molecular weight (MW) and Dex content were found to have strong impact on the PK/BD profiles of P−Dex. The increase of MW (14,000, 24,000, and 42,000 g/mol) and Dex content (0, 151, and 313 μmol/g) enhances the arthrotropism of P−Dex. For the conjugate with highest MW and Dex content (P−H-MW/Dex), the percentage of injected doses per gram (ID/g) of ankle synovial tissue at day seventh postadministration is 1% g−1, which confirms P−Dex as an arthrotropic macromolecular prodrug. For liver and spleen, the ID/g values are 0.51 and 3.64% g−1, respectively. As an antigen-presenting organ, the sequestration of t...