title: On prilled Nanotubes-in-Microgel Oral Systems for protein delivery.
abstract: Newly discovered active macromolecules are highly promising for therapy, but poor bioavailability hinders their oral use. Microencapsulation approaches, such as protein prilling into microspheres, may enable protection from gastrointestinal (GI) enzymatic degradation. This would increase bioavailability mainly for local delivery to GI lumen or mucosa. This work's purpose was to design a novel architecture, namely a Nanotubes-in-Microgel Oral System, by prilling for protein delivery. Halloysite nanotubes (HNT) were selected as orally acceptable clay particles and their lumen was enlarged by alkaline etching. This chemical modification increased the luminal volume to a mean of 216.3 μL g(-1) (+40.8%). After loading albumin as model drug, the HNT were entrapped in microgels by prilling. The formation of Nanoparticles-in-Microsphere Oral System (NiMOS) yielded entrapment efficiencies up to 63.2%. NiMOS shape was spherical to toroidal, with a diameter smaller than 320 μm. Release profiles depended largely on the employed system and HNT type. Protein stability was determined throughout prilling and after in vitro enzymatic degradation. Prilling did not harm protein structure, and NiMOS demonstrated higher enzymatic protection than pure nanotubes or microgels, since up to 82% of BSA remained unscathed after in vitro digestion. Therefore, prilled NiMOS was shown to be a promising and flexible multi-compartment system for oral (local) macromolecular delivery.
authors: Department of Pharmaceutical Sciences, University of Basel, 4056 Basel, Switzerland; Institute of Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, 4132 Muttenz, Switzerland.
authors: Jan Kendall
authors: JK
authors: de Kruif
authors: Department of Pharmaceutical Sciences, University of Basel, 4056 Basel, Switzerland.
authors: Gisela
authors: G
authors: Ledergerber
authors: Institute of Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, 4132 Muttenz, Switzerland; Department of Pediatric Surgery and Department of Clinical Research, Inselspital, Bern University Hospital, Bern, Switzerland.
authors: Carla
authors: C
authors: Garofalo
authors: Institute of Chemistry and Bioanalytics, University of Applied Sciences and Arts Northwestern Switzerland, 4132 Muttenz, Switzerland; Department of Biomedicine, University of Basel, 4031 Basel, Switzerland; Department of Pediatric Surgery and Department of Clinical Research, Inselspital, Bern University Hospital, Bern, Switzerland.
authors: Elizaveta
authors: E
authors: Fasler-Kan
authors: Institute of Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, 4132 Muttenz, Switzerland. Electronic address: martin.kuentz@fhnw.ch.
authors: Martin
authors: M
authors: Kuentz
mesh_terms: D000284:Administration, Oral; D000538:Aluminum Silicates / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D000077215:Clay; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods; D005782:Gels / Q000737:chemistry*; D008863:Microspheres; D053758:Nanoparticles / Q000737:chemistry; D043942:Nanotubes / Q000737:chemistry*; D010316:Particle Size; D011506:Proteins / Q000737:chemistry*
chemical_list: D000538:Aluminum Silicates; D005782:Gels; D011506:Proteins; D000077215:Clay
keywords: Halloysite; Hydrogels; Macromolecular drug delivery; Multi-compartment system; Nanocomposite; Nanotubes; NiMOS; Oral protein delivery; Prilling