Surface engineered nanoliposomal platform for selective lymphatic uptake of asenapine maleate: In vitro and in vivo studies

Renuka S. Managuli, Julie Tzu Wen Wang, Farid Muhammad Faruqu, Abhjieet Pandey, Sanyog Jain, Khuloud T. Al-Jamal, Srinivas Mutalik

Research output: Contribution to journalArticle

Abstract

Asenapine maleate (ASPM) is an antipsychotic drug prescribed for the treatment of schizophrenia and bipolar disorder. ASPM possesses low oral bioavailability due to extensive hepatic metabolism. Therefore, RGD peptide conjugated liposomes loaded with ASPM were prepared to target Peyer's patches in the intestine which in-turn get access into intestinal lymphatic system thereby increasing the oral bioavailability of the drug. Liposomes were evaluated for size, zeta potential, differential scanning calorimetry (DSC), FTIR spectroscopy, X-ray diffraction (XRD), shape and morphology, in vitro drug release, cell line studies, everted intestinal uptake, pharmacodynamics, pharmacokinetics, tissue distribution, targetability and stability studies. In vitro drug release study showed the sustained release of drug from the formulations. Optimized liposomes (size <110 nm) showed greater permeability across the Caco2 + Raji B co-culture model in vitro and everted rat ileum ex vivo. Liposomes showed increase in bioavailability and high efficacy in reducing the L-DOPA-carbidopa induced locomotor count compared to plain drug. Liposomes also showed high concentration of drug in the brain after their oral administration. Imaging studies showed that RGD peptide conjugated liposomes were successful in targeting the Peyer's patches, both in vivo and ex vivo. The study successfully demonstrated the improved pharmacokinetics and efficacy profile of ASPM by using a ligand conjugated targeted liposomal system.

Original languageEnglish
Article number110620
JournalMaterials Science and Engineering C
Volume109
DOIs
Publication statusPublished - 04-2020

Fingerprint

maleates
Liposomes
drugs
platforms
bioavailability
Pharmaceutical Preparations
Pharmacokinetics
Peptides
peptides
Pharmacodynamics
Carbidopa
schizophrenia
intestines
Zeta potential
lymphatic system
Metabolism
Antipsychotic Agents
metabolism
Asenapine
Rats

All Science Journal Classification (ASJC) codes

  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanics of Materials
  • Mechanical Engineering

Cite this

Managuli, Renuka S. ; Wang, Julie Tzu Wen ; Faruqu, Farid Muhammad ; Pandey, Abhjieet ; Jain, Sanyog ; Al-Jamal, Khuloud T. ; Mutalik, Srinivas. / Surface engineered nanoliposomal platform for selective lymphatic uptake of asenapine maleate : In vitro and in vivo studies. In: Materials Science and Engineering C. 2020 ; Vol. 109.
@article{361de07980ee43859c83072db5a1531b,
title = "Surface engineered nanoliposomal platform for selective lymphatic uptake of asenapine maleate: In vitro and in vivo studies",
abstract = "Asenapine maleate (ASPM) is an antipsychotic drug prescribed for the treatment of schizophrenia and bipolar disorder. ASPM possesses low oral bioavailability due to extensive hepatic metabolism. Therefore, RGD peptide conjugated liposomes loaded with ASPM were prepared to target Peyer's patches in the intestine which in-turn get access into intestinal lymphatic system thereby increasing the oral bioavailability of the drug. Liposomes were evaluated for size, zeta potential, differential scanning calorimetry (DSC), FTIR spectroscopy, X-ray diffraction (XRD), shape and morphology, in vitro drug release, cell line studies, everted intestinal uptake, pharmacodynamics, pharmacokinetics, tissue distribution, targetability and stability studies. In vitro drug release study showed the sustained release of drug from the formulations. Optimized liposomes (size <110 nm) showed greater permeability across the Caco2 + Raji B co-culture model in vitro and everted rat ileum ex vivo. Liposomes showed increase in bioavailability and high efficacy in reducing the L-DOPA-carbidopa induced locomotor count compared to plain drug. Liposomes also showed high concentration of drug in the brain after their oral administration. Imaging studies showed that RGD peptide conjugated liposomes were successful in targeting the Peyer's patches, both in vivo and ex vivo. The study successfully demonstrated the improved pharmacokinetics and efficacy profile of ASPM by using a ligand conjugated targeted liposomal system.",
author = "Managuli, {Renuka S.} and Wang, {Julie Tzu Wen} and Faruqu, {Farid Muhammad} and Abhjieet Pandey and Sanyog Jain and Al-Jamal, {Khuloud T.} and Srinivas Mutalik",
year = "2020",
month = "4",
doi = "10.1016/j.msec.2019.110620",
language = "English",
volume = "109",
journal = "Materials Science and Engineering C",
issn = "0928-4931",
publisher = "Elsevier BV",

}

Surface engineered nanoliposomal platform for selective lymphatic uptake of asenapine maleate : In vitro and in vivo studies. / Managuli, Renuka S.; Wang, Julie Tzu Wen; Faruqu, Farid Muhammad; Pandey, Abhjieet; Jain, Sanyog; Al-Jamal, Khuloud T.; Mutalik, Srinivas.

In: Materials Science and Engineering C, Vol. 109, 110620, 04.2020.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Surface engineered nanoliposomal platform for selective lymphatic uptake of asenapine maleate

T2 - In vitro and in vivo studies

AU - Managuli, Renuka S.

AU - Wang, Julie Tzu Wen

AU - Faruqu, Farid Muhammad

AU - Pandey, Abhjieet

AU - Jain, Sanyog

AU - Al-Jamal, Khuloud T.

AU - Mutalik, Srinivas

PY - 2020/4

Y1 - 2020/4

N2 - Asenapine maleate (ASPM) is an antipsychotic drug prescribed for the treatment of schizophrenia and bipolar disorder. ASPM possesses low oral bioavailability due to extensive hepatic metabolism. Therefore, RGD peptide conjugated liposomes loaded with ASPM were prepared to target Peyer's patches in the intestine which in-turn get access into intestinal lymphatic system thereby increasing the oral bioavailability of the drug. Liposomes were evaluated for size, zeta potential, differential scanning calorimetry (DSC), FTIR spectroscopy, X-ray diffraction (XRD), shape and morphology, in vitro drug release, cell line studies, everted intestinal uptake, pharmacodynamics, pharmacokinetics, tissue distribution, targetability and stability studies. In vitro drug release study showed the sustained release of drug from the formulations. Optimized liposomes (size <110 nm) showed greater permeability across the Caco2 + Raji B co-culture model in vitro and everted rat ileum ex vivo. Liposomes showed increase in bioavailability and high efficacy in reducing the L-DOPA-carbidopa induced locomotor count compared to plain drug. Liposomes also showed high concentration of drug in the brain after their oral administration. Imaging studies showed that RGD peptide conjugated liposomes were successful in targeting the Peyer's patches, both in vivo and ex vivo. The study successfully demonstrated the improved pharmacokinetics and efficacy profile of ASPM by using a ligand conjugated targeted liposomal system.

AB - Asenapine maleate (ASPM) is an antipsychotic drug prescribed for the treatment of schizophrenia and bipolar disorder. ASPM possesses low oral bioavailability due to extensive hepatic metabolism. Therefore, RGD peptide conjugated liposomes loaded with ASPM were prepared to target Peyer's patches in the intestine which in-turn get access into intestinal lymphatic system thereby increasing the oral bioavailability of the drug. Liposomes were evaluated for size, zeta potential, differential scanning calorimetry (DSC), FTIR spectroscopy, X-ray diffraction (XRD), shape and morphology, in vitro drug release, cell line studies, everted intestinal uptake, pharmacodynamics, pharmacokinetics, tissue distribution, targetability and stability studies. In vitro drug release study showed the sustained release of drug from the formulations. Optimized liposomes (size <110 nm) showed greater permeability across the Caco2 + Raji B co-culture model in vitro and everted rat ileum ex vivo. Liposomes showed increase in bioavailability and high efficacy in reducing the L-DOPA-carbidopa induced locomotor count compared to plain drug. Liposomes also showed high concentration of drug in the brain after their oral administration. Imaging studies showed that RGD peptide conjugated liposomes were successful in targeting the Peyer's patches, both in vivo and ex vivo. The study successfully demonstrated the improved pharmacokinetics and efficacy profile of ASPM by using a ligand conjugated targeted liposomal system.

UR - http://www.scopus.com/inward/record.url?scp=85077797745&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85077797745&partnerID=8YFLogxK

U2 - 10.1016/j.msec.2019.110620

DO - 10.1016/j.msec.2019.110620

M3 - Article

AN - SCOPUS:85077797745

VL - 109

JO - Materials Science and Engineering C

JF - Materials Science and Engineering C

SN - 0928-4931

M1 - 110620

ER -