TY - JOUR

T1 - Animal models for evaluation of oral delivery of biopharmaceuticals

AU - Harloff-Helleberg, Stine

AU - Nielsen, Line Hagner

AU - Nielsen, Hanne Mørck

PY - 2017/12

Y1 - 2017/12

N2 - Biopharmaceuticals are increasingly important for patients and the pharmaceutical industry due to their ability to treat and, in some cases, even cure chronic and potentially life-threatening diseases. Most biopharmaceuticals are administered by injection, but intensive focus on development of systems for oral delivery of biopharmaceuticals may result in new treatment modalities to increase the patient compliance and reduce product cost. In the preclinical development phase, use of experimental animal models is essential for evaluation of new formulation designs. In general, the limited oral bioavailability of biopharmaceuticals, of just a few percent, is expected, and therefore, the animal models and the experimental settings must be chosen with utmost care. More knowledge and focus on this topic is highly needed, despite experience from the numerous studies evaluating animal models for oral drug delivery of small molecule drugs. This review highlights and discusses pros and cons of the most currently used animal models and settings. Additionally, it also looks into the influence of anesthetics and sampling methods for evaluation of drug delivery systems for oral delivery of biopharmaceuticals primarily with examples on insulin.

AB - Biopharmaceuticals are increasingly important for patients and the pharmaceutical industry due to their ability to treat and, in some cases, even cure chronic and potentially life-threatening diseases. Most biopharmaceuticals are administered by injection, but intensive focus on development of systems for oral delivery of biopharmaceuticals may result in new treatment modalities to increase the patient compliance and reduce product cost. In the preclinical development phase, use of experimental animal models is essential for evaluation of new formulation designs. In general, the limited oral bioavailability of biopharmaceuticals, of just a few percent, is expected, and therefore, the animal models and the experimental settings must be chosen with utmost care. More knowledge and focus on this topic is highly needed, despite experience from the numerous studies evaluating animal models for oral drug delivery of small molecule drugs. This review highlights and discusses pros and cons of the most currently used animal models and settings. Additionally, it also looks into the influence of anesthetics and sampling methods for evaluation of drug delivery systems for oral delivery of biopharmaceuticals primarily with examples on insulin.

KW - In situ perfusion

KW - In vivo

KW - Insulin

KW - Macromolecules

KW - Peptides

KW - Proteins

U2 - 10.1016/j.jconrel.2017.09.025

DO - 10.1016/j.jconrel.2017.09.025

M3 - Review

C2 - 28935596

AN - SCOPUS:85031502209

VL - 268

SP - 57

EP - 71

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -