PMID- 33811278
OWN - NLM
STAT- MEDLINE
DCOM- 20211108
LR  - 20211108
IS  - 1573-904X (Electronic)
IS  - 0724-8741 (Linking)
VI  - 38
IP  - 4
DP  - 2021 Apr
TI  - Multiphysics Modeling and Simulation of Subcutaneous Injection and Absorption of 
      Biotherapeutics: Model Development.
PG  - 607-624
LID - 10.1007/s11095-021-03032-w [doi]
AB  - PURPOSE: Many monoclonal antibodies (mAbs) are administered via subcutaneous (SC) 
      injection. Local transport and absorption kinetics and mechanisms, however, 
      remain poorly understood. A multiphysics computational model was developed to 
      simulate the injection and absorption processes of a protein solution in the SC 
      tissue. METHODS: Quantitative relationships among tissue properties and transport 
      behaviors of an injected solution were described by respective physical laws. SC 
      tissue was treated as a 3-dimensional homogenous, poroelastic medium, in which 
      vasculatures and lymphatic vessels were implicitly treated. Tissue deformation 
      was considered, and interstitial fluid flow was modeled by Darcy's law. Transport 
      of the drug mass was described based on diffusion and advection, which was 
      integrated with tissue mechanics and interstitial fluid dynamics. RESULTS: 
      Injection and absorption of albumin and IgG solutions were simulated. Upon 
      injection, a sharp rise in tissue pressure, porosity, and fluid velocity could be 
      observed at the injection tip. Largest tissue deformation appeared at the model 
      surface. Transport of drug mass out of the injection zone was minimal. Absorption 
      by local lymphatics was found to last several weeks. CONCLUSIONS: A bottom-up 
      method was developed to simulate drug transport and absorption of protein 
      solutions in skin tissue base on physical principles. The results appear to match 
      experimental observations.
FAU - Zheng, Fudan
AU  - Zheng F
AD  - Department of Industrial and Physical Pharmacy, Purdue University, 525 Stadium 
      Mall Dr., RHPH Building, West Lafayette, Indiana, 47907, USA.
FAU - Hou, Peng
AU  - Hou P
AD  - Department of Industrial and Physical Pharmacy, Purdue University, 525 Stadium 
      Mall Dr., RHPH Building, West Lafayette, Indiana, 47907, USA.
FAU - Corpstein, Clairissa D
AU  - Corpstein CD
AD  - Department of Industrial and Physical Pharmacy, Purdue University, 525 Stadium 
      Mall Dr., RHPH Building, West Lafayette, Indiana, 47907, USA.
FAU - Xing, Lei
AU  - Xing L
AD  - Department of Engineering Science, University of Oxford, Oxford, OX1 3PJ, UK.
FAU - Li, Tonglei
AU  - Li T
AD  - Department of Industrial and Physical Pharmacy, Purdue University, 525 Stadium 
      Mall Dr., RHPH Building, West Lafayette, Indiana, 47907, USA. tonglei@purdue.edu.
LA  - eng
PT  - Journal Article
DEP - 20210402
PL  - United States
TA  - Pharm Res
JT  - Pharmaceutical research
JID - 8406521
RN  - 0 (Antibodies, Monoclonal)
SB  - IM
MH  - Absorption, Physiological
MH  - Antibodies, Monoclonal/administration & dosage/*pharmacokinetics
MH  - Biological Availability
MH  - Computer Simulation
MH  - Humans
MH  - Injections, Subcutaneous
MH  - *Models, Biological
MH  - Subcutaneous Tissue/*metabolism
OTO - NOTNLM
OT  - computational fluid dynamics
OT  - pharmacokinetics
OT  - protein absorption
OT  - subcutaneous biomechanics
OT  - subcutaneous injection
EDAT- 2021/04/04 06:00
MHDA- 2021/11/09 06:00
CRDT- 2021/04/03 05:52
PHST- 2020/12/16 00:00 [received]
PHST- 2021/03/16 00:00 [accepted]
PHST- 2021/04/04 06:00 [pubmed]
PHST- 2021/11/09 06:00 [medline]
PHST- 2021/04/03 05:52 [entrez]
AID - 10.1007/s11095-021-03032-w [pii]
AID - 10.1007/s11095-021-03032-w [doi]
PST - ppublish
SO  - Pharm Res. 2021 Apr;38(4):607-624. doi: 10.1007/s11095-021-03032-w. Epub 2021 Apr 
      2.