Patterned Drug-Eluting Coatings for Tracheal Stents Based on PLA, PLGA, and PCL for the Granulation Formation Reduction: In Vivo Studies

Abstract

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.

“Smart” Polylactic Acid Films with Ceftriaxone Loaded Microchamber Arrays for Personalized Antibiotic Therapy

“…In general, according to our data, we can conclude that such "smart films" with microchamber arrays are a promising biomaterial that can be used as dressing or coating to modify the surface of implants and stents [31,60]. In addition, it can allow the mechanical protection of damaged skin and tissues, prolonged and triggered antibiotic release.…”

“…The use of hydrophobic polymers deposited by a single layer dip-coating approach for MCA fabrication was proposed [29]. The exploitation of water-insoluble polymers, such as PLA [29][30][31], poly(lactic-co-glycolic acid) (PLGA) [31,32], polycaprolactone (PCL) [31,33], resulted in significantly faster, simpler, and scalable approach enable to entrap and retain water-soluble molecules. PLA polymer-made MCAs exhibit sufficient mechanical properties to keep structural parameters avoiding unnecessary deformation, facilitate loading due to smooth surface, and improve cargo retain compared to PCL and PLGA [31].…”

“…The exploitation of water-insoluble polymers, such as PLA [29][30][31], poly(lactic-co-glycolic acid) (PLGA) [31,32], polycaprolactone (PCL) [31,33], resulted in significantly faster, simpler, and scalable approach enable to entrap and retain water-soluble molecules. PLA polymer-made MCAs exhibit sufficient mechanical properties to keep structural parameters avoiding unnecessary deformation, facilitate loading due to smooth surface, and improve cargo retain compared to PCL and PLGA [31]. In vitro and in vivo studies have shown that such PLA-based MCAs are completely biocompatible and biodegradable [29,34,35].…”

“…In vitro and in vivo studies have shown that such PLA-based MCAs are completely biocompatible and biodegradable [29,34,35]. MCAs are suitable for carrying a wide range of substances with different molecular weights, in particular, enzymes [30], polysaccharides [36], fluorescent dyes [37], neurotransmitters [34], hormones [31,32], and growth factors [35]. The studies have shown that polymer film with MCAs is sensitive to external stimuli such as ultrasound [29,30,32,38], magnetic field [39], and laser irradiation [30,36,40,41] if additional modifiers are used during their fabrication (magnetic nanoparticles and photoabsorbing agents, respectively).…”

“…Thus, the sensitivity of MCAs to ultrasound makes it possible to control the release of the drug and individually select the therapy regimes. This promising "smart" biomaterial can be used as a dressing or coating to modify the surface of implants and stents [31,46] to provide mechanical protection, prolonged and controlled drug release.…”