Patterned Drug-Eluting Coatings for Tracheal Stents Based on PLA, PLGA, and PCL for the Granulation Formation Reduction: In Vivo Studies
Olga A. Sindeeva,
Ekaterina S. Prikhozhdenko,
Igor Schurov,
Nikolay Sedykh,
Sergey Goriainov,
Arfenya Karamyan,
Ekaterina A. Mordovina,
Olga A. Inozemtseva,
Valeriya Kudryavtseva,
Leonid E. Shchesnyak,
Rimma A. Abramovich,
Sergey Mikhajlov,
Gleb B. Sukhorukov
Affiliations
Olga A. Sindeeva
Skolkovo Innovation Center, Skolkovo Institute of Science and Technology, 3 Nobel Str., 143005 Moscow, Russia
Ekaterina S. Prikhozhdenko
Science Medical Center, Saratov State University, 83 Astrakhanskaya Str., 410012 Saratov, Russia
Igor Schurov
Innovative Engineering Technologies Institute, Peoples Friendship University of Russia (RUDN University), 6 Mikluho-Maklaya Str., 117198 Moscow, Russia
Nikolay Sedykh
Innovative Engineering Technologies Institute, Peoples Friendship University of Russia (RUDN University), 6 Mikluho-Maklaya Str., 117198 Moscow, Russia
Sergey Goriainov
Innovative Engineering Technologies Institute, Peoples Friendship University of Russia (RUDN University), 6 Mikluho-Maklaya Str., 117198 Moscow, Russia
Arfenya Karamyan
Innovative Engineering Technologies Institute, Peoples Friendship University of Russia (RUDN University), 6 Mikluho-Maklaya Str., 117198 Moscow, Russia
Ekaterina A. Mordovina
Science Medical Center, Saratov State University, 83 Astrakhanskaya Str., 410012 Saratov, Russia
Olga A. Inozemtseva
Science Medical Center, Saratov State University, 83 Astrakhanskaya Str., 410012 Saratov, Russia
Valeriya Kudryavtseva
Nanoforce Ltd., School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London E1 4NS, UK
Leonid E. Shchesnyak
Innovative Engineering Technologies Institute, Peoples Friendship University of Russia (RUDN University), 6 Mikluho-Maklaya Str., 117198 Moscow, Russia
Rimma A. Abramovich
Innovative Engineering Technologies Institute, Peoples Friendship University of Russia (RUDN University), 6 Mikluho-Maklaya Str., 117198 Moscow, Russia
Sergey Mikhajlov
Innovative Engineering Technologies Institute, Peoples Friendship University of Russia (RUDN University), 6 Mikluho-Maklaya Str., 117198 Moscow, Russia
Gleb B. Sukhorukov
Nanoforce Ltd., School of Engineering and Materials Science, Queen Mary University of London, Mile End Road, London E1 4NS, UK
Expandable metallic stent placement is often the only way to treat airway obstructions. Such treatment with an uncoated stent causes granulation proliferation and subsequent restenosis, resulting in the procedure’s adverse complications. Systemic administration of steroids drugs in high dosages slows down granulation tissue overgrowth but leads to long-term side effects. Drug-eluting coatings have been used widely in cardiology for many years to suppress local granulation and reduce the organism’s systemic load. Still, so far, there are no available analogs for the trachea. Here, we demonstrate that PLA-, PCL- and PLGA-based films with arrays of microchambers to accommodate therapeutic substances can be used as a drug-eluting coating through securely fixing on the surface of an expandable nitinol stent. PCL and PLA were most resistant to mechanical damage associated with packing in delivery devices and making it possible to keep high-molecular-weight cargo. Low-molecular-weight methylprednisolone sodium succinate is poorly retained in PCL- and PLGA-based microchambers after immersion in deionized water (only 9.5% and 15.7% are left, respectively). In comparison, PLA-based microchambers retain 96.3% after the same procedure. In vivo studies on rabbits have shown that effective granulation tissue suppression is achieved when PLA and PLGA are used for coatings. PLGA-based microchamber coating almost completely degrades in 10 days in the trachea, while PLA-based microchamber films partially preserve their structure. The PCL-based film coating is most stable over time, which probably causes blocking the outflow of fluid from the tracheal mucosa and the aggravation of the inflammatory process against the background of low drug concentration. Combination and variability of polymers in the fabrication of films with microchambers to retain therapeutic compounds are suggested as a novel type of drug-eluting coating.
