School of Life and Health Sciences, Aston University, Birmingham, B4 7ET, UK.
J Control Release. 2012 Jul 20;161(2):389-98. doi: 10.1016/j.jconrel.2012.01.020. Epub 2012 Jan 24.
Generally, we like to see ageing as a process that is happening to people older than ourselves. However the process of ageing impacts on a wide range of functions within the human body. Whilst many of the outcomes of ageing can now be delayed or reduced, age-related changes in cellular, molecular and physiological functionality of tissues and organs can also influence how drugs enter, distribute and are eliminated from the body. Therefore, the changing profile of barriers to drug delivery should be considered if we are to develop more age-appropriate medicines. Changes in the drug dissolution and absorption in older patients may require the formulation of oral delivery systems that offer enhanced retention at absorption sites to improve drug delivery. Alternatively, liquid and fast-melt dosage systems may address the need of patients who have difficulties in swallowing medication. Ageing-induced changes in the lung can also result in slower drug absorption, which is further compounded by disease factors, common in an ageing population, that reduce lung capacity. In terms of barriers to drug delivery to the eye, the main consideration is the tear film, which like other barriers to drug delivery, changes with normal ageing and can impact on the bioavailability of drugs delivery using eye drops and suspensions. In contrast, whilst the skin as a barrier changes with age, no significant difference in absorption of drugs from transdermal drug delivery is observed in different age groups. However, due to the age-related pharmacokinetic and pharmacodynamic changes, dose adaptation should still be considered for drug delivery across the skin. Overall it is clear that the increasing age demographic of most populations, presents new (or should that be older) barriers to effective drug delivery.
一般来说,我们倾向于将衰老视为发生在老年人身上的过程。然而,衰老过程会影响人体的多种功能。虽然现在许多衰老的结果可以被延迟或减少,但组织和器官的细胞、分子和生理功能的与年龄相关的变化也会影响药物进入、分布和从体内消除的方式。因此,如果我们要开发更适合年龄的药物,就应该考虑药物输送的不断变化的障碍。老年患者的药物溶解和吸收的变化可能需要开发具有增强在吸收部位保留能力的口服给药系统,以改善药物输送。或者,液体和速溶剂量系统可以满足吞咽药物有困难的患者的需求。肺部的衰老诱导变化也会导致药物吸收缓慢,而在老龄化人群中常见的降低肺容量的疾病因素进一步加剧了这种情况。就药物输送到眼睛的障碍而言,主要考虑因素是泪膜,就像其他药物输送障碍一样,它会随着正常衰老而变化,并会影响使用眼药水和混悬剂输送药物的生物利用度。相比之下,尽管皮肤作为屏障会随年龄而变化,但在不同年龄组中,从透皮药物输送中吸收药物没有明显差异。然而,由于与年龄相关的药代动力学和药效学变化,仍然应该考虑通过皮肤输送药物时的剂量调整。总的来说,很明显,大多数人群的年龄人口统计学的增加,为有效的药物输送带来了新的(或者应该说是更老的)障碍。