Pharmacokinetic and biodistribution studies of a bone-targeting drug delivery system based on N-(2-hydroxypropyl)methacrylamide copolymers

Osteotropicity of novel bone-targeted HPMA copolymer conjugates has been demonstrated previously with bone histomorphometric analysis. The pharmacokinetics and biodistribution of this delivery system were investigated in the current study with healthy young BALB/c mice. The ¹²⁵l-labeled bone-targeted and control (nontargeted) HPMA copolymers were administered intravenously to mice, and their distribution to different organs and tissues was followed using a γ counter and single photon emission computed tomography (SPECT). Both the invasive and noninvasive data further confirmed that the incorporation of D-aspartic acid octapeptide (D-Asp₈) as bone-targeting moiety could favorably deposit the HPMA copolymers to the entire skeleton, especially to the high bone turnover sites. To evaluate the influence of molecular weight, three fractions (M_w of 24, 46, and 96 KDa) of HPMA copolymer-D-Asp₈ conjugate were prepared and evaluated. Higher molecular weight of the conjugate enhanced the deposition to bone due to the prolonged half-life in circulation, but it weakened the bone selectivity. A higher content of bone-targeting moiety (D-Asp₈) in the conjugate is desirable to achieve superior hard tissue selectivity. Further validation of the bone-targeting efficacy of the conjugates in animal models of osteoporosis and other skeletal diseases is needed in the future.