The oral bioavailability of hydrophilic and macromolecular drugs is generally poor owing to their poor membrane permeability. For example, peptide and protein drugs are poorly absorbed because of their low stability and poor membrane permeability in the gastrointestinal tract. Consequently, these drugs can be clinically administered only via injection. However, such frequent administration of injections subjects the patients to considerable pain, along with increasing the possibility of serious side effects.

Several approaches have been examined to overcome the delivery problems associated with the poorly absorbed drugs. These include (1) use of additives such as absorption enhancers and protease inhibitors, (2) modification of the chemical structure of drugs to produce prodrugs and analogs, (3) application of dosage forms to entrap these poorly absorbed drugs, and (4) development of novel and alternative administration methods (apart from oral and parenteral administration). We examined these approaches and demonstrated their effectiveness in improving intestinal and transmucosal absorption of several poorly absorbed drugs. These approaches may provide useful and basic information to improve the intestinal and transmucosal absorption of poorly absorbed drugs including peptide and protein drugs.

亲水性和大分子药物的口服生物利用度由于其膜渗透性差而通常较差。例如，肽和蛋白质药物由于其稳定性低和在胃肠道中的膜通透性差而难以吸收。因此，这些药物只能通过注射在临床上给药。然而，这种频繁的注射给药使患者遭受相当大的痛苦，同时增加了严重副作用的可能性。

为了克服与吸​​收不良的药物有关的递送问题，已经研究了几种方法。这些措施包括（1）使用诸如吸收增强剂和蛋白酶抑制剂之类的添加剂；（2）改变药物的化学结构以生产前药和类似物；（3）施用剂型以捕获这些吸收不良的药物；以及（4）开发新的和替代的给药方法（除了口服和肠胃外给药）。我们检查了这些方法，并证明了它们在改善几种吸收不良的药物对肠道和粘膜的吸收中的有效性。这些方法可提供有用和基本的信息，以改善吸收不良的药物（包括肽和蛋白质药物）在肠道和粘膜的吸收。