PMID- 30077735
OWN - NLM
STAT- MEDLINE
DCOM- 20191015
LR  - 20191015
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Linking)
VI  - 286
DP  - 2018 Sep 28
TI  - Subcutaneous delivery of monoclonal antibodies: How do we get there?
PG  - 301-314
LID - S0168-3659(18)30453-X [pii]
LID - 10.1016/j.jconrel.2018.08.001 [doi]
AB  - The convenience of subcutaneous (SC) administration and the increasing interest 
      in monoclonal antibody (mAb)-based therapies for chronic diseases, hint their 
      potential for SC delivery in a near future. In addition, there is a common 
      interest among patients, clinicians and pharmaceutical industry in moving from 
      intravenous to SC administration of mAbs due to benefits of improved patient 
      compliance and reduced costs to the healthcare system. Despite the wide use of 
      this route of administration in diseases like diabetes and rheumatoid arthritis, 
      SC bioavailability of mAbs has been shown to be incomplete and variable in most 
      preclinical and clinical studies. This evidences a gap in the understanding of SC 
      absorption process of mAbs and in their drug development process. Likewise, 
      challenges present in drug formulation, such as high viscosity and aggregation, 
      and the inherent immunogenicity of mAbs have also been hampering the successful 
      translation to clinical settings. This review provides a characterization of the 
      subcutaneously delivered mAbs that have entered the market in the last 10 years 
      as well as a snapshot of the landscape of currently undergoing clinical trials. 
      Moreover, there is an overview of the factors influencing SC absorption of mAbs 
      and the preclinical models in use to study SC pharmacokinetics. Considerations 
      about drug formulation and immunogenicity of mAbs are also explored.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Viola, Margarida
AU  - Viola M
AD  - Faculty of Pharmacy, University of Coimbra, Portugal.
FAU - Sequeira, Joana
AU  - Sequeira J
AD  - Faculty of Pharmacy, University of Coimbra, Portugal; I3S - Institute for 
      Research and Innovation in Health, University of Porto, Portugal.
FAU - Seica, Raquel
AU  - Seica R
AD  - Institute of Physiology, iCBR-Coimbra Institute for Clinical and Biomedical 
      Research, Coimbra, Portugal.
FAU - Veiga, Francisco
AU  - Veiga F
AD  - Faculty of Pharmacy, University of Coimbra, Portugal; REQUIMTE/LAQV, Group of 
      Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Coimbra, 
      Portugal.
FAU - Serra, Joao
AU  - Serra J
AD  - Grupo Tecnimede, Sintra, Portugal.
FAU - Santos, Ana C
AU  - Santos AC
AD  - Faculty of Pharmacy, University of Coimbra, Portugal; REQUIMTE/LAQV, Group of 
      Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Coimbra, 
      Portugal.
FAU - Ribeiro, Antonio J
AU  - Ribeiro AJ
AD  - Faculty of Pharmacy, University of Coimbra, Portugal; I3S - Institute for 
      Research and Innovation in Health, University of Porto, Portugal. Electronic 
      address: aribeiro@ff.uc.pt.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20180802
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Antibodies, Monoclonal)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/*administration & dosage/pharmacokinetics
MH  - Drug Compounding/methods
MH  - Drug Delivery Systems/methods
MH  - Humans
MH  - Injections, Subcutaneous
MH  - Subcutaneous Absorption
MH  - Subcutaneous Tissue/metabolism
OTO - NOTNLM
OT  - Animal model
OT  - Bioavailability
OT  - Clinical trials
OT  - Drug delivery
OT  - Monoclonal antibody (mAb)
OT  - Subcutaneous
EDAT- 2018/08/06 06:00
MHDA- 2019/10/16 06:00
CRDT- 2018/08/06 06:00
PHST- 2018/04/28 00:00 [received]
PHST- 2018/07/30 00:00 [revised]
PHST- 2018/08/01 00:00 [accepted]
PHST- 2018/08/06 06:00 [pubmed]
PHST- 2019/10/16 06:00 [medline]
PHST- 2018/08/06 06:00 [entrez]
AID - S0168-3659(18)30453-X [pii]
AID - 10.1016/j.jconrel.2018.08.001 [doi]
PST - ppublish
SO  - J Control Release. 2018 Sep 28;286:301-314. doi: 10.1016/j.jconrel.2018.08.001. 
      Epub 2018 Aug 2.