Drug delivery for bioactive polysaccharides to improve their drug-like properties and curative efficacy.

Over several decades, natural polysaccharides (PSs) have been actively exploited for their wide bioactivities. So far, many PS-related reviews have been published; however, none focused on the delivery of bioactive PSs as therapeutic molecules. Herein, we summarized and discussed general pharmacokinetic properties of PSs and drug delivery systems (DDSs) developed for them, together with the challenges and prospects. Overall, most bioactive PSs suffer from undesirable pharmacokinetic attributes, which negatively affect their efficacy and clinical use. Various DDSs therefore have been being utilized to improve the drug-like properties and curative efficacy of bioactive PSs by means of improving oral absorption, controlling the release, enhancing the in vivo retention ability, targeting the delivery, exerting synergistic effects, and so on. Specifically, nano-sized insoluble DDSs were mainly applied to improve the oral absorption and target delivery of PSs, among which liposome was especially suitable for immunoregulatory and/or anti-ischemic PSs due to its synergistic effects in immunoregulation and biomembrane repair. Chemical conjugation of PSs was mainly utilized to improve their oral absorption and/or prolong their blood residence. With formulation flexibility, in situ forming systems alone or in combination with drug conjugation could be used to achieve day(s)- or month(s)-long sustained delivery of PSs per dosing.