口服途径是大多数药物的首选给药方式,其治疗成功与否直接关系到复方肠吸收。这个吸收过程,反过来,受影响药物生物利用度的几个因素的影响,这是极其依赖于最大的溶解度和渗透性。然而,优化这最后两个因素,没有化学结构修饰,具有挑战性。虽然聚(酰胺基胺)树枝状聚合物(PAMAM)作为药物递送化合物是一种创新和有前途的策略,很少有研究确定PAMAM-药物衍生物的渗透性和溶解度。考虑到这种情况,本文旨在对最近五年有关树枝状聚合物传递系统的生物制药特性进行文献综述。体外方法学,如平行人工膜通透性测定(PAMPA)(非基于细胞的模型)和Caco-2细胞(基于细胞的模型),在药物发现的早期阶段用于渗透性评估被证明是最有前途的方法。因此,我们讨论过,例如,通过PAMPA的使用,有可能评估TAT缀合的PAMAM的DNA经皮递送的更高容量,当与具有P<0.05的未修饰的PAMAM树枝状聚合物相比时。我们还提出了选择最佳的生物制药表征方法的重要性,这对于保证候选药物的有效性和安全性至关重要。
The oral route is the preferred way of drug administration for most drugs, whose treatment success is directly related to the compound intestinal absorption. This absorption process, in its turn, is influenced by several factors impacting the drug bioavailability, which is extremely dependent on the maximum solubility and permeability. However, optimizing these last two factors, without chemical structural modification, is challenging. Although poly(amidoamine) dendrimers (
PAMAM) are an innovative and promising strategy as drug delivery compounds, there are few studies that determine the permeability and solubility of
PAMAM-drugs derivatives. Considering this scenario, this paper aimed to carry out a literature
review of the last five years concerning biopharmaceutical characterizations of dendrimer delivery systems. In vitro methodologies, such as the Parallel artificial membrane permeability assay (PAMPA) (non-cellular based model) and Caco-2 cells (cellular based model), used for the permeability evaluation in the early stages of drug discovery proved to be the most promising methodologies. As a result, we discussed, for instance, that through the usage of PAMPA it was possible to evaluate the higher capacity for transdermal delivery of DNA of TAT-conjugated
PAMAM, when in comparison with unmodified
PAMAM dendrimer with a P<0.05. We also presented the importance of choosing the best methods of biopharmaceutical characterization, which will be essential to guarantee the efficacy and safety of the drug candidate.