Acknowledgements

commodities with promising prospects. And in the coming years, great progress will be made in PDDS research by the development of drug delivery devices and phar-

The PDDS constructed with biomaterials has been a hot research direction in medicine and pharmacy fields for decades. Among these biomaterials, CS, which is the only natural cationic polysaccharide, has been recognized as one of the most versatile and promising functional biomaterials. Moreover, CS is also one of the most abundant regeneration resources, second only to the cellulose. After decades of research, CS has been recognized as a nontoxic, biocompatible (especially with respiratory cells) and biodegradable polymer. Moreover, CS can accommodate both hydrophilic and hydrophobic drugs due to its amphiphilic properties [5]. The excellent performances of CS as a building component of DDS have been confirmed by many studies, and it has been identified as a novel drug delivery carrier with broad application prospects, especially for sustained and controlled drug release. Due to the unique features, CS can assist the drugs accomplishing local and systemic delivery, realizing high mucoadhesion, and efficient drug absorption in target tissues, which is especially applicative for PDDS. However, CS is insoluble in aqueous solutions at neutral and alkaline pH, and it only can be dissolved in aqueous acidic media (pH < 5). This frustrating issue has badly limited CS's application range, and there is an urgent need for developing convenient and practical modification strategies to improve its solubility. Up to now, CS has been approved as safe by US-FDA and EU for dietary use and wound dressing applications [85]. And additionally, CS has only been approved by the European Pharmacopeia as a pharmaceutical excipient for oral preparations. The safety issues of CS and its derivatives in pulmonary delivery and other administration routes have not been fully understood and still remain to be further evaluated. Therefore, the safety issue is a noteworthy research gap remained to be filled in the future work, for figuring out the potential adverse effects of CS and its derivatives in humans. At the same time, appropriate engineering of designing and modifying CS and its derivatives is highly demanded to optimize the performance of the CS-based drug carriers, for meeting the special requirements of in vivo pulmonary drug delivery. We hope that in the near future, more advanced synthesis and modification methods will be developed. And in the meanwhile, the physicochemical property, toxicity, biodistribution, biocompatibility, and biodegradability of CS and

its derivatives should also be thoroughly investigated in detail.

systemic disease treatment in the near future.

Despite all this, CS-based PDDS has already achieved considerable success in the past decades. It is believed that in the near future, with the rapid development of material science, biotechnology, genetic engineering, medical technology, and other scientific fields, people will have a more extensive and in-depth understanding of the unique properties of CS and its derivatives. We hope that more efficient CSbased PDDS will be designed, by developing novel material preparation strategies, advanced formulation methods, and improved inhalation technology. We believe that CS-based PDDS will play more important roles in the applications of local and

5. Conclusions

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maceutical preparation technology.

Role of Novel Drug Delivery Vehicles in Nanobiomedicine

The authors are thankful to the generous financial support from the National Natural Science Foundation of China (81774125) and National Key Technology R&D Program of the Ministry of Science and Technology (2013GA740103).
