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Review
. 2018 Jul 4;10(3):83.
doi: 10.3390/pharmaceutics10030083.

Overview of Antibody Drug Delivery

Sahar Awwad  1   2 , Ukrit Angkawinitwong  3
Affiliations
Review

Overview of Antibody Drug Delivery

Sahar Awwad et al. Pharmaceutics. .

Abstract

Monoclonal antibodies (mAbs) are one of the most important classes of therapeutic proteins, which are used to treat a wide number of diseases (e.g., oncology, inflammation and autoimmune diseases). Monoclonal antibody technologies are continuing to evolve to develop medicines with increasingly improved safety profiles, with the identification of new drug targets being one key barrier for new antibody development. There are many opportunities for developing antibody formulations for better patient compliance, cost savings and lifecycle management, e.g., subcutaneous formulations. However, mAb-based medicines also have limitations that impact their clinical use; the most prominent challenges are their short pharmacokinetic properties and stability issues during manufacturing, transport and storage that can lead to aggregation and protein denaturation. The development of long acting protein formulations must maintain protein stability and be able to deliver a large enough dose over a prolonged period. Many strategies are being pursued to improve the formulation and dosage forms of antibodies to improve efficacy and to increase the range of applications for the clinical use of mAbs.

Keywords: antibodies; drug delivery; pharmacokinetics; protein; stability.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
A schematic diagram representing the modular structure of a monoclonal antibody (mAb). (Abbreviation: CDR: complementarity-determining region; COO-: carboxy terminal; CH: constant domain, heavy chain, CL: constant domain, light chain; Fab: fragment antigen-binding; Fc: fragment crystallisable region, NH3: amino terminal end, S-S: disulfide bond; VH: variable domain, heavy chain; VL: variable domain, light chain)
Figure 2
Figure 2
A schematic diagram illustrating neonatal Fc receptor (FcRn) recycling pathway: (1) Immunoglobulin G (IgGs) are internaliszed into endocytic vesicles. (2) Endosome becomes acidic resulting in the binding of Fc domain to FcRn. (3) Bound IgG are recycled back to the cell membrane and (4) IgG dissociates at neutral pH (7.4) from FcRn and is released back into the blood.
Figure 3
Figure 3
Small-mAb derived fragment technologies and next generation mAbs. (a) Recombinant fragment antigen-binding (Fab), (b) Single-chain variable fragment (scFv) and (c) bispecific mAb platforms. The latter can comprise two covalently linked heterogenous IgG (IgG2) or heterogenous Fab domains (F(ab’)2).
Figure 4
Figure 4
Common formulation strategies used to prolong protein release.
Figure 5
Figure 5
Methods to increase the duration of action of proteins.
See this image and copyright information in PMC

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