Botulinum neurotoxin type A (BoNT-A) is the active substance in pharmaceutical prepa-rations widely used worldwide for the highly effective treatment of various disorders. Among the three commercial formulations of BoNT-A currently available in Italy for neurological indications, abobotulinum A toxin (Dysport®, Ipsen SpA, Milano, Italy) and incobotulinum A toxin (Xeomin®, Merz Pharma Italia srl, Milano, Italy) differ in the content of neurotoxin, non-toxic protein, and excipients. Clinical applications of BoNT-A adopt extremely diluted solutions (10−6 mg/mL) for injection in the target body district. Near-infrared spectroscopy (NIRS) and chemometrics allow rapid, non-invasive, and non-destructive methods for qualitative and quantitative analysis. No data are available to date on the chemometric analysis of the spectral fingerprints acquired from the diluted commercial formulations of BoNT-A. In this proof-of-concept study, we tested whether NIRS can categorize solutions of incobotulinum A toxin (lacking non-toxic proteins) and abobotulinum A toxin (containing non-toxic proteins). Distinct excipients in the two formulations were also analyzed. We acquired transmittance spectra in the visible and short-wave infrared regions (350–2500 nm) by an ASD FieldSpec 4™ Standard-Res Spectrophotoradiometer, using a submerged dip probe designed to read spectra in transflectance mode from liquid samples. After preliminary spectra pre-processing, principal component analysis was applied to characterize the spectral features of the two BoNT-A solutions and those of the various excipients diluted according to clinical standards. Partial least squares-discriminant analysis was used to implement a classification model able to discriminate the BoNT-A solutions and excipients. NIRS distinguished solutions containing distinct BoNT-A commercial formulations (abobotulinum A toxin vs. incobotulinum A toxin) diluted at recommended volumes for clinical reconstitution, distinct proteins (HSA vs. incobotulinum A toxin), very diluted solutions of simple sugars (lactose vs. sucrose), and saline or water. Predictive models of botulinum toxin formulations were also performed with the highest precision and accuracy.

Near-infrared transflectance spectroscopy discriminates solutions containing two commercial formulations of botulinum toxin type A diluted at recommended volumes for clinical reconstitution / Curra, A.; Gasbarrone, R.; Bonifazi, G.; Serranti, S.; Fattapposta, F.; Trompetto, C.; Marinelli, L.; Missori, P.; Lendaro, E.. - In: BIOSENSORS. - ISSN 2079-6374. - 12:4(2022), pp. 216-239. [10.3390/bios12040216]

Near-infrared transflectance spectroscopy discriminates solutions containing two commercial formulations of botulinum toxin type A diluted at recommended volumes for clinical reconstitution

Curra A.;Gasbarrone R.
;
Bonifazi G.;Serranti S.;Fattapposta F.;Missori P.;Lendaro E.
2022

Abstract

Botulinum neurotoxin type A (BoNT-A) is the active substance in pharmaceutical prepa-rations widely used worldwide for the highly effective treatment of various disorders. Among the three commercial formulations of BoNT-A currently available in Italy for neurological indications, abobotulinum A toxin (Dysport®, Ipsen SpA, Milano, Italy) and incobotulinum A toxin (Xeomin®, Merz Pharma Italia srl, Milano, Italy) differ in the content of neurotoxin, non-toxic protein, and excipients. Clinical applications of BoNT-A adopt extremely diluted solutions (10−6 mg/mL) for injection in the target body district. Near-infrared spectroscopy (NIRS) and chemometrics allow rapid, non-invasive, and non-destructive methods for qualitative and quantitative analysis. No data are available to date on the chemometric analysis of the spectral fingerprints acquired from the diluted commercial formulations of BoNT-A. In this proof-of-concept study, we tested whether NIRS can categorize solutions of incobotulinum A toxin (lacking non-toxic proteins) and abobotulinum A toxin (containing non-toxic proteins). Distinct excipients in the two formulations were also analyzed. We acquired transmittance spectra in the visible and short-wave infrared regions (350–2500 nm) by an ASD FieldSpec 4™ Standard-Res Spectrophotoradiometer, using a submerged dip probe designed to read spectra in transflectance mode from liquid samples. After preliminary spectra pre-processing, principal component analysis was applied to characterize the spectral features of the two BoNT-A solutions and those of the various excipients diluted according to clinical standards. Partial least squares-discriminant analysis was used to implement a classification model able to discriminate the BoNT-A solutions and excipients. NIRS distinguished solutions containing distinct BoNT-A commercial formulations (abobotulinum A toxin vs. incobotulinum A toxin) diluted at recommended volumes for clinical reconstitution, distinct proteins (HSA vs. incobotulinum A toxin), very diluted solutions of simple sugars (lactose vs. sucrose), and saline or water. Predictive models of botulinum toxin formulations were also performed with the highest precision and accuracy.
2022
botulinum neurotoxin type A; chemomet-rics; NIR spectroscopy; partial least squares-discriminant analysis; transflectance spectroscopy; discriminant analysis; excipients; neurotoxins; spectroscopy; near-infrared; botulinum toxins; type A
01 Pubblicazione su rivista::01a Articolo in rivista
Near-infrared transflectance spectroscopy discriminates solutions containing two commercial formulations of botulinum toxin type A diluted at recommended volumes for clinical reconstitution / Curra, A.; Gasbarrone, R.; Bonifazi, G.; Serranti, S.; Fattapposta, F.; Trompetto, C.; Marinelli, L.; Missori, P.; Lendaro, E.. - In: BIOSENSORS. - ISSN 2079-6374. - 12:4(2022), pp. 216-239. [10.3390/bios12040216]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1634286
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