title: Mucoadhesive intestinal devices for oral delivery of salmon calcitonin.
abstract: One of the major challenges faced by therapeutic polypeptides remains their invasive route of delivery. Oral administration offers a potential alternative to injections; however, this route cannot be currently used for peptides due to their limited stability in the stomach and poor permeation across the intestine. Here, we report mucoadhesive devices for oral delivery that are inspired by the design of transdermal patches and demonstrate their capabilities in vivo for salmon calcitonin (sCT). The mucoadhesive devices were prepared by compressing a polymeric matrix containing carbopol, pectin and sodium carboxymethylcellulose (1:1:2), and were coated on all sides but one with an impermeable and flexible ethyl cellulose (EC) backing layer. Devices were tested for in vitro dissolution, mucoadhesion to intestinal mucosa, enhancement of drug absorption in vitro (Caco-2 monolayer transport) and in vivo in rats. Devices showed steady drug release with ≈75% cumulative drug released in 5h. Devices also demonstrated strong mucoadhesion to porcine small intestine to withstand forces up to 100 times their own weight. sCT-loaded mucoadhesive devices exhibited delivery of sCT across Caco-2 monolayers and across the intestinal epithelium in vivo in rats. A ≈52-fold (pharmacokinetic) and ≈44-fold (pharmacological) enhancement of oral bioavailability was observed with mucoadhesive devices when compared to direct intestinal injections. Oral delivery of devices in enteric coated capsules resulted in significant bioavailability enhancement.
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara 93106, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Gupta
authors.forename: Byeong Hee
authors.initials: BH
authors.lastname: Hwang
authors.forename: Joohee
authors.initials: J
authors.lastname: Lee
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Anselmo
authors.forename: Nishit
authors.initials: N
authors.lastname: Doshi
authors.forename: Samir
authors.initials: S
authors.lastname: Mitragotri
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000268:Adhesiveness; D000284:Administration, Oral; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018938:Caco-2 Cells; D002116:Calcitonin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000295:instrumentation*; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D010368:Pectins / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine
chemical_list: D000180:Acrylic Resins; D050071:Bone Density Conservation Agents; D004337:Drug Carriers; C006912:carboxypolymethylene; C028815:salmon calcitonin; D010368:Pectins; D002116:Calcitonin; D002266:Carboxymethylcellulose Sodium
keywords: Enteric coated capsule; Intestinal; Macromolecule; Oral; Patch; Peroral