title: Formulating the alginate-polyornithine biocapsule for prolonged stability: evaluation of composition and manufacturing technique.
abstract: Alginate encapsulation is one of the most widely used techniques for introducing cell-based therapeutics into the body. Numerous encapsulation methodologies exist, utilizing a variety of alginates, purification technologies, and unique polycationic membrane components. The stability of a conventional alginate formulation encapsulated using a commercially available technique and apparatus has been characterized extensively. The current study employs an encapsulation protocol and ultra-pure alginate pioneered at the University of Perugia. The enhanced microcapsules were produced, characterized, and implanted into the brain, peritoneal cavity, and subcutaneous space of Long-Evans rats. After 14, 28, 60, 90, 120, and 180 or 215 days, capsules were explanted and the surface was analyzed using Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Image analysis was carried out to measure changes in diameter and wall thickness. FTIR peak analysis and surface morphology from SEM indicated that the enhanced encapsulation technique and formulation produced a stable biocapsule capable of survival in all sites, including the harsh peritoneal environment, for at least 215 days. Preimplant analysis showed a marked increase in the structural integrity of the enhanced formulation with improved elasticity and burst strength compared with the baseline formulation, which remained stable for less than 60 days. The enhanced microcapsule composition showed advantages in physical strength and longevity, indicating that small changes in encapsulation methodologies and materials selection can dramatically impact the stability and longevity of alginate microcapsules and their contents.
authors.affiliation: LCT BioPharma, Incorporated, Providence, Rhode Island 02906, USA. cgthanos@gmail.com
authors.forename: C G
authors.initials: CG
authors.lastname: Thanos
authors.forename: R
authors.initials: R
authors.lastname: Calafiore
authors.forename: G
authors.initials: G
authors.lastname: Basta
authors.forename: B E
authors.initials: BE
authors.lastname: Bintz
authors.forename: W J
authors.initials: WJ
authors.lastname: Bell
authors.forename: J
authors.initials: J
authors.lastname: Hudak
authors.forename: A
authors.initials: A
authors.lastname: Vasconcellos
authors.forename: P
authors.initials: P
authors.lastname: Schneider
authors.forename: S J M
authors.initials: SJ
authors.lastname: Skinner
authors.forename: M
authors.initials: M
authors.lastname: Geaney
authors.forename: P
authors.initials: P
authors.lastname: Tan
authors.forename: R B
authors.initials: RB
authors.lastname: Elliot
authors.forename: M
authors.initials: M
authors.lastname: Tatnell
authors.forename: L
authors.initials: L
authors.lastname: Escobar
authors.forename: H
authors.initials: H
authors.lastname: Qian
authors.forename: E
authors.initials: E
authors.lastname: Mathiowitz
authors.forename: D F
authors.initials: DF
authors.lastname: Emerich
mesh_terms: D000464:Alginates / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D002214:Capsules / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D002850:Chromatography, Gel; D020723:Glucuronic Acid / Q000737:chemistry / Q000378:metabolism; D006603:Hexuronic Acids / Q000737:chemistry / Q000378:metabolism; D008027:Light; D008297:Male; D008422:Materials Testing / Q000379:methods*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D010537:Peritoneum / Q000648:ultrastructure; D019736:Prostheses and Implants; D051381:Rats; D020318:Rats, Long-Evans; D012542:Scattering, Radiation; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; D002214:Capsules; D006603:Hexuronic Acids; D010455:Peptides; C008973:polyornithine; D020723:Glucuronic Acid