PMID- 36228881
OWN - NLM
STAT- MEDLINE
DCOM- 20221115
LR  - 20221115
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Linking)
VI  - 628
DP  - 2022 Nov 25
TI  - Physicochemical surrogates for in vitro toxicity assessment of liposomal 
      amphotericin B.
PG  - 122273
LID - S0378-5173(22)00828-6 [pii]
LID - 10.1016/j.ijpharm.2022.122273 [doi]
AB  - Pharmaceutical toxicity evaluations often use in vitro systems involving primary 
      cells, cell lines or red blood cells (RBCs). Cell-based analyses ('bioassays') 
      can be cumbersome and typically rely on hard-to-standardize biological materials. 
      Amphotericin B (AmB) toxicity evaluations are primarily based on potassium 
      release from RBCs and share these limitations. This study evaluates the potential 
      substitution of two physicochemical AmB toxicity approaches for the bioassay: 
      Ultraviolet-visible spectroscopy (UV-vis) and in vitro drug release kinetics. 
      UV-vis spectral analyses indicated that liposomal AmB's (L-AmB) main peak 
      position (lambda(max)) and peak ratio (OD(346)/OD(322)) are potential toxicity 
      surrogates. Similarly, two first-order release parameters derived from USP-4 in 
      vitro drug release analyses also provided linear relationships with toxicity. 
      These were the initial, overall drug release rate and the ratio of loose to tight 
      AmB pools. Positive slopes and high correlation coefficients (R(2) > 0.9) 
      characterized all interrelations between physicochemical parameters and toxicity. 
      These tests converted the manufacturing variables' nonlinear (i.e., curvilinear) 
      relationships with in vitro toxicity to linear responses. Three different 
      toxicity attenuation approaches (2 manufacturing, 1 formulation), covering 
      formulation composition and process aspects, support this approach's 
      universality. These data suggest that one or more spectral and kinetic 
      physicochemical tests can be surrogates for L-AmB in vitro toxicity testing.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Marx, Richard
AU  - Marx R
AD  - Landrau Scientific Innovations, 22 Laurel Street, Leominster, MA 01453, USA.
FAU - Lee, Jaeweon
AU  - Lee J
AD  - Landrau Scientific Innovations, 22 Laurel Street, Leominster, MA 01453, USA.
FAU - Svirkin, Yuri
AU  - Svirkin Y
AD  - Landrau Scientific Innovations, 22 Laurel Street, Leominster, MA 01453, USA.
FAU - Yoon, Seongkyu
AU  - Yoon S
AD  - Department of Chemical Engineering, University of Massachusetts Lowell, 1 
      University Ave, Lowell, MA, 01854, USA. Electronic address: 
      Seongkyu_Yoon@uml.edu.
FAU - Landrau, Nelson
AU  - Landrau N
AD  - Landrau Scientific Innovations, 22 Laurel Street, Leominster, MA 01453, USA.
FAU - Abul Kaisar, Md
AU  - Abul Kaisar M
AD  - Food and Drug Administration, Center for Drug Evaluation and Research, Office of 
      Generic Drugs, Office of Research and Standards, 10903 New Hampshire Avenue, 
      Silver Spring, MD 20993, USA.
FAU - Qin, Bin
AU  - Qin B
AD  - Food and Drug Administration, Center for Drug Evaluation and Research, Office of 
      Generic Drugs, Office of Research and Standards, 10903 New Hampshire Avenue, 
      Silver Spring, MD 20993, USA.
FAU - Park, Jin H
AU  - Park JH
AD  - Food and Drug Administration, Center for Drug Evaluation and Research, Office of 
      Generic Drugs, Office of Research and Standards, 10903 New Hampshire Avenue, 
      Silver Spring, MD 20993, USA.
FAU - Alam, Khondoker
AU  - Alam K
AD  - Food and Drug Administration, Center for Drug Evaluation and Research, Office of 
      Generic Drugs, Office of Research and Standards, 10903 New Hampshire Avenue, 
      Silver Spring, MD 20993, USA.
FAU - Kozak, Darby
AU  - Kozak D
AD  - Food and Drug Administration, Center for Drug Evaluation and Research, Office of 
      Generic Drugs, Office of Research and Standards, 10903 New Hampshire Avenue, 
      Silver Spring, MD 20993, USA.
FAU - Wang, Yan
AU  - Wang Y
AD  - Food and Drug Administration, Center for Drug Evaluation and Research, Office of 
      Generic Drugs, Office of Research and Standards, 10903 New Hampshire Avenue, 
      Silver Spring, MD 20993, USA.
FAU - Xu, Xiaoming
AU  - Xu X
AD  - Food and Drug Administration, Center for Drug Evaluation and Research, Office of 
      Pharmaceutical Quality, Office of Testing and Research, 10903 New Hampshire 
      Avenue, Silver Spring, MD 20993, USA.
FAU - Zheng, Jiwen
AU  - Zheng J
AD  - Food and Drug Administration, Center for Devices and Radiological Health, Office 
      of Science and Engineering Laboratories, 10903 New Hampshire Avenue, Silver 
      Spring, MD 20993, USA.
FAU - Rivnay, Benjamin
AU  - Rivnay B
AD  - Landrau Scientific Innovations, 22 Laurel Street, Leominster, MA 01453, USA.
LA  - eng
PT  - Journal Article
DEP - 20221011
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (liposomal amphotericin B)
RN  - 7XU7A7DROE (Amphotericin B)
RN  - 0 (Antifungal Agents)
RN  - 0 (Liposomes)
SB  - IM
MH  - *Amphotericin B/toxicity/chemistry
MH  - *Antifungal Agents/toxicity/chemistry
MH  - Liposomes
MH  - Drug Liberation
OTO - NOTNLM
OT  - Aggregation
OT  - Amphotericin B
OT  - Drug release kinetics
OT  - In vitro toxicity
OT  - Liposomes
OT  - Surrogate test
OT  - UV-vis spectra
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/10/14 06:00
MHDA- 2022/11/16 06:00
CRDT- 2022/10/13 19:36
PHST- 2022/07/07 00:00 [received]
PHST- 2022/09/28 00:00 [revised]
PHST- 2022/10/03 00:00 [accepted]
PHST- 2022/10/14 06:00 [pubmed]
PHST- 2022/11/16 06:00 [medline]
PHST- 2022/10/13 19:36 [entrez]
AID - S0378-5173(22)00828-6 [pii]
AID - 10.1016/j.ijpharm.2022.122273 [doi]
PST - ppublish
SO  - Int J Pharm. 2022 Nov 25;628:122273. doi: 10.1016/j.ijpharm.2022.122273. Epub 
      2022 Oct 11.