LC–MS/MS study of in vivo fate of hyaluronan polymeric micelles carrying doxorubicin

• Published in: Carbohydrate polymers 2019-04, Vol.209, p.181-189
• Main Authors: Šimek, Matěj, Hermannová, Martina, Šmejkalová, Daniela, Foglová, Tereza, Souček, Karel, Binó, Lucia, Velebný, Vladimír
• Format: Article
• Language: English
• Subjects: Biodistribution; Doxorubicin; Hyaluronan; Pharmacokinetics; Polymeric micelles
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2018.12.104

•Developed LC–MS/MS method is suitable for biodistribution study of nanocarrier.•Both the polymer matrix and the drug are estimated after one sample handling.•Pharmacokinetics of loaded HA-C18:1 nanocarrier was successfully evaluated in vivo.•HA-C18:1 was fully biodegradable and eliminated within 72 h.•Increased tumour targeting was observed despite rapid nanocarrier disintegration. A better understanding of in vivo behavior of nanocarriers is necessary for further improvement in their development. Here we present a novel approach, where both the matrix and the drug can be analyzed by LCMS/MS after one sample handling. The developed method was applied for the comparison of pharmacokinetic profile of free and encapsulated doxorubicin (DOX) in oleyl hyaluronan (HA-C18:1) polymeric micelles. The results indicated that nanocarriers were rapidly dissociated upon in vivo administration. Despite this fact, the administration of encapsulated DOX led to its longer circulation time and enhanced tumor targeting. This effect was not observed injecting blank HA-C18:1 micelles followed by unencapsulated DOX. Biodistribution studies and molecular weight estimation of the carrier matrix indicated relatively high stability of HA-C18:1 ester bond in bloodstream and complete elimination of the derivative within 72 h. The proposed methodology provides a novel strategy to elucidate the pharmacokinetic behavior of polysaccharide-based drug delivery systems.