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New Peceol™/Span™ 60 Niosomes Coated with Chitosan for Candesartan Cilexetil: Perspective Increase in Absolute Bioavailability in Rats.
Int J Nanomedicine. 2021; 16:5581-5601.IJ

Abstract

PURPOSE

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.

Authors+Show Affiliations

Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34429601

Citation

AbuElfadl, Aya, et al. "New Peceol™/Span™ 60 Niosomes Coated With Chitosan for Candesartan Cilexetil: Perspective Increase in Absolute Bioavailability in Rats." International Journal of Nanomedicine, vol. 16, 2021, pp. 5581-5601.
AbuElfadl A, Boughdady M, Meshali M. New Peceol™/Span™ 60 Niosomes Coated with Chitosan for Candesartan Cilexetil: Perspective Increase in Absolute Bioavailability in Rats. Int J Nanomedicine. 2021;16:5581-5601.
AbuElfadl, A., Boughdady, M., & Meshali, M. (2021). New Peceol™/Span™ 60 Niosomes Coated with Chitosan for Candesartan Cilexetil: Perspective Increase in Absolute Bioavailability in Rats. International Journal of Nanomedicine, 16, 5581-5601. https://doi.org/10.2147/IJN.S324171
AbuElfadl A, Boughdady M, Meshali M. New Peceol™/Span™ 60 Niosomes Coated With Chitosan for Candesartan Cilexetil: Perspective Increase in Absolute Bioavailability in Rats. Int J Nanomedicine. 2021;16:5581-5601. PubMed PMID: 34429601.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - New Peceol™/Span™ 60 Niosomes Coated with Chitosan for Candesartan Cilexetil: Perspective Increase in Absolute Bioavailability in Rats. AU - AbuElfadl,Aya, AU - Boughdady,Mariza, AU - Meshali,Mahasen, Y1 - 2021/08/16/ PY - 2021/06/10/received PY - 2021/07/29/accepted PY - 2021/8/25/entrez PY - 2021/8/26/pubmed PY - 2021/10/21/medline KW - PROSOLV® KW - candesartan cilexetil KW - chitosan KW - glyceryl monooleate KW - niosomes SP - 5581 EP - 5601 JF - International journal of nanomedicine JO - Int J Nanomedicine VL - 16 N2 - PURPOSE: 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. SN - 1178-2013 UR - https://www.unboundmedicine.com/medline/citation/34429601/New_Peceol™/Span™_60_Niosomes_Coated_with_Chitosan_for_Candesartan_Cilexetil:_Perspective_Increase_in_Absolute_Bioavailability_in_Rats_ L2 - https://dx.doi.org/10.2147/IJN.S324171 DB - PRIME DP - Unbound Medicine ER -