Departamento de Farmacia, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA Córdoba, Argentina.
Eur J Pharm Sci. 2013 Jul 16;49(4):588-94. doi: 10.1016/j.ejps.2013.04.023. Epub 2013 May 6.
With the aim to provide more rational basis about the potentiality of hyaluronic acid (or hyaluronan) as drug carrier a set of ionic complexes of its acid form (HA) and its sodium salt (NaHA) with three model drugs (D) (atenolol, propranolol and lidocaine) were prepared. Besides NaHA subjected to hyalurodinase depolimerization (NaHA(d)) was also used. Transparent dispersions were obtained. They exhibited negative electrokinetic potential and a high degree of counterionic condensation with affinity constants (log Kcc) in the range of 5.8-6.1 for propranolol complexes (pK(a) 9.45) and 4.0-4.6 for lidocaine ones (pK(a) 7.92). Delivery rates of D from the complexes were measured in a Franz-type bicompartimental device. Loaded D were slowly released from the three types of complexes, even when a neutral salt was added to the dispersion placed in the donor compartment, revealing the high affinity between the protonated drugs and the ionisable groups of the polymer. Complex dispersions based on HA or on NaHA(d) exhibited lower viscosity than those of NaHA but their complexing ability remained unaltered. The results reported on equilibrium and release properties of Hyaluronan-model D complexes contribute to expand the use of HA and NaHA as drug carriers for different routes of administration.
为了提供更多关于透明质酸（或透明质酸钠）作为药物载体的潜力的合理依据，制备了其酸形式（HA）和其钠盐（NaHA）与三种模型药物（D）（阿替洛尔、普萘洛尔和利多卡因）的一系列离子复合物。还使用了经透明质酸酶解聚（NaHA(d)）的 NaHA。得到了透明分散体。它们表现出负动电潜力和高度的抗衡离子凝聚，对于普萘洛尔复合物（pK(a) 9.45）的亲和常数（log Kcc）在 5.8-6.1 范围内，对于利多卡因复合物（pK(a) 7.92）的亲和常数（log Kcc）在 4.0-4.6 范围内。在 Franz 型双室装置中测量了 D 从复合物中的释放速率。即使在将中性盐添加到放置在供体隔室中的分散体中，D 也从三种类型的复合物中缓慢释放，这表明质子化药物与聚合物可离子化基团之间具有高亲和力。基于 HA 或 NaHA(d)的复合物分散体的粘度低于 NaHA 的粘度，但它们的络合能力保持不变。关于透明质酸-模型 D 复合物的平衡和释放特性的报告结果有助于扩大 HA 和 NaHA 作为不同给药途径的药物载体的用途。
