New Peceol™/Span™ 60 Niosomes Coated with Chitosan for Candesartan Cilexetil: Perspective Increase in Absolute Bioavailability in Rats
Aya AbuElfadl, Mariza Boughdady, Mahasen Meshali Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, EgyptCorrespondence: Aya AbuElfadlDepartment of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Gomhoreyah St, Mansoura, 35516, EgyptTel +201004602870Fax +20 50...
Guardado en:
| Autores principales: | , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/dc7d03120c4f4fa49bec06bd764421c2 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:dc7d03120c4f4fa49bec06bd764421c2 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:dc7d03120c4f4fa49bec06bd764421c22021-12-02T16:39:47ZNew Peceol™/Span™ 60 Niosomes Coated with Chitosan for Candesartan Cilexetil: Perspective Increase in Absolute Bioavailability in Rats1178-2013https://doaj.org/article/dc7d03120c4f4fa49bec06bd764421c22021-08-01T00:00:00Zhttps://www.dovepress.com/new-peceolspan-60-niosomes-coated-with-chitosan-for-candesartan-cilexe-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Aya AbuElfadl, Mariza Boughdady, Mahasen Meshali Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, EgyptCorrespondence: Aya AbuElfadlDepartment of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Gomhoreyah St, Mansoura, 35516, EgyptTel +201004602870Fax +20 50 224 7496Email aya_mh9244@mans.edu.egPurpose: Candesartan cilexetil (CC), a prodrug of candesartan (CDT), is a class II BCS drug that suffers from poor oral bioavailability because of low aqueous solubility, P-gp efflux and first-pass metabolism. The absolute bioavailability reported for CC was only 15% and the methods to increase it remain elusive, thus the aim of our work was to prepare new CC-loaded niosomes encompassing, for the first time, glycerol monooleate GMO (Peceol™), as P-gp efflux inhibitor and promoter of lymphatic transport with Span™ 60 as bioenhancer. The prepared niosomes were further coated with chitosan for augmenting the CC oral absorption.Methods: The niosomes were prepared by thin film hydration method through quality by design approach, using two levels of each of three critical process parameters (CPPs), namely, XA (the molar ratio of surfactant mixture to cholesterol) at a ratio of 1:1 or 2:1; XB (the molar ratio of Span™ 60 to Peceol™) at a ratio of 1:1 or 2:1; and XC (the drug amount) at 15 mg or 30 mg. The investigated critical quality attributes (CQAs) were entrapment efficiency percent, particle size, and polydispersity index. The optimized uncoated and chitosan coated formulations were subjected to DSC and stability study. In vitro drug release, biocompatibility with Caco-2 cells and lastly the absolute bioavailability evaluation in rats were assessed.Results: The physical properties of the optimized and stable niosomes were satisfactory. The ingredients were compatible with each other and biocompatible with Caco-2 cells. The synergistic combination of Peceol™ and Span™ 60 probably surmounted the P-gp efflux with an increase in oral absolute bioavailability of niosomes to five times that of CC suspension.Conclusion: The new niosomal formulations of CC containing Peceol™ with Span™ 60 and cholesterol either uncoated or coated with chitosan were a successful paradigm in achieving high oral absolute bioavailability and increased Caco-2 cells biocompatibility.Keywords: candesartan cilexetil, glyceryl monooleate, chitosan, niosomes, PROSOLV꺫uElfadl ABoughdady MMeshali MDove Medical Pressarticlecandesartan cilexetilglyceryl monooleatechitosanniosomesprosolvMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 5581-5601 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
candesartan cilexetil glyceryl monooleate chitosan niosomes prosolv Medicine (General) R5-920 |
| spellingShingle |
candesartan cilexetil glyceryl monooleate chitosan niosomes prosolv Medicine (General) R5-920 AbuElfadl A Boughdady M Meshali M New Peceol™/Span™ 60 Niosomes Coated with Chitosan for Candesartan Cilexetil: Perspective Increase in Absolute Bioavailability in Rats |
| description |
Aya AbuElfadl, Mariza Boughdady, Mahasen Meshali Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, EgyptCorrespondence: Aya AbuElfadlDepartment of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Gomhoreyah St, Mansoura, 35516, EgyptTel +201004602870Fax +20 50 224 7496Email aya_mh9244@mans.edu.egPurpose: Candesartan cilexetil (CC), a prodrug of candesartan (CDT), is a class II BCS drug that suffers from poor oral bioavailability because of low aqueous solubility, P-gp efflux and first-pass metabolism. The absolute bioavailability reported for CC was only 15% and the methods to increase it remain elusive, thus the aim of our work was to prepare new CC-loaded niosomes encompassing, for the first time, glycerol monooleate GMO (Peceol™), as P-gp efflux inhibitor and promoter of lymphatic transport with Span™ 60 as bioenhancer. The prepared niosomes were further coated with chitosan for augmenting the CC oral absorption.Methods: The niosomes were prepared by thin film hydration method through quality by design approach, using two levels of each of three critical process parameters (CPPs), namely, XA (the molar ratio of surfactant mixture to cholesterol) at a ratio of 1:1 or 2:1; XB (the molar ratio of Span™ 60 to Peceol™) at a ratio of 1:1 or 2:1; and XC (the drug amount) at 15 mg or 30 mg. The investigated critical quality attributes (CQAs) were entrapment efficiency percent, particle size, and polydispersity index. The optimized uncoated and chitosan coated formulations were subjected to DSC and stability study. In vitro drug release, biocompatibility with Caco-2 cells and lastly the absolute bioavailability evaluation in rats were assessed.Results: The physical properties of the optimized and stable niosomes were satisfactory. The ingredients were compatible with each other and biocompatible with Caco-2 cells. The synergistic combination of Peceol™ and Span™ 60 probably surmounted the P-gp efflux with an increase in oral absolute bioavailability of niosomes to five times that of CC suspension.Conclusion: The new niosomal formulations of CC containing Peceol™ with Span™ 60 and cholesterol either uncoated or coated with chitosan were a successful paradigm in achieving high oral absolute bioavailability and increased Caco-2 cells biocompatibility.Keywords: candesartan cilexetil, glyceryl monooleate, chitosan, niosomes, PROSOLV® |
| format |
article |
| author |
AbuElfadl A Boughdady M Meshali M |
| author_facet |
AbuElfadl A Boughdady M Meshali M |
| author_sort |
AbuElfadl A |
| title |
New Peceol™/Span™ 60 Niosomes Coated with Chitosan for Candesartan Cilexetil: Perspective Increase in Absolute Bioavailability in Rats |
| title_short |
New Peceol™/Span™ 60 Niosomes Coated with Chitosan for Candesartan Cilexetil: Perspective Increase in Absolute Bioavailability in Rats |
| title_full |
New Peceol™/Span™ 60 Niosomes Coated with Chitosan for Candesartan Cilexetil: Perspective Increase in Absolute Bioavailability in Rats |
| title_fullStr |
New Peceol™/Span™ 60 Niosomes Coated with Chitosan for Candesartan Cilexetil: Perspective Increase in Absolute Bioavailability in Rats |
| title_full_unstemmed |
New Peceol™/Span™ 60 Niosomes Coated with Chitosan for Candesartan Cilexetil: Perspective Increase in Absolute Bioavailability in Rats |
| title_sort |
new peceol™/span™ 60 niosomes coated with chitosan for candesartan cilexetil: perspective increase in absolute bioavailability in rats |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/dc7d03120c4f4fa49bec06bd764421c2 |
| work_keys_str_mv |
AT abuelfadla newpeceoltradespantrade60niosomescoatedwithchitosanforcandesartancilexetilperspectiveincreaseinabsolutebioavailabilityinrats AT boughdadym newpeceoltradespantrade60niosomescoatedwithchitosanforcandesartancilexetilperspectiveincreaseinabsolutebioavailabilityinrats AT meshalim newpeceoltradespantrade60niosomescoatedwithchitosanforcandesartancilexetilperspectiveincreaseinabsolutebioavailabilityinrats |
| _version_ |
1718383604136935424 |