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Papain-Decorated Mucopenetrating SEDDS: A Tentative Approach to Combat Absorption Issues of Acyclovir via the Oral Route
The aim of the current study was to enhance the oral bioavailability of Acyclovir (ACV) based on the papain-functionalized self-emulsifying drug delivery systems (SEDDS). The optimum control SEDDS formulation comprised of kolliphore (40%), transcutol (30%), propylene glycol (20%) and oleoyl chloride...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9412565/ https://www.ncbi.nlm.nih.gov/pubmed/36015210 http://dx.doi.org/10.3390/pharmaceutics14081584 |
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author | Mahmood, Arshad Haneef, Rabbia Al Meslamani, Ahmad Z. Bostanudin, Mohammad F. Sohail, Muhammad Sarfraz, Muhammad Arafat, Mosab |
author_facet | Mahmood, Arshad Haneef, Rabbia Al Meslamani, Ahmad Z. Bostanudin, Mohammad F. Sohail, Muhammad Sarfraz, Muhammad Arafat, Mosab |
author_sort | Mahmood, Arshad |
collection | PubMed |
description | The aim of the current study was to enhance the oral bioavailability of Acyclovir (ACV) based on the papain-functionalized self-emulsifying drug delivery systems (SEDDS). The optimum control SEDDS formulation comprised of kolliphore (40%), transcutol (30%), propylene glycol (20%) and oleoyl chloride (10%). However, in the targeted SEDDS formulation, oleoyl chloride was replaced with oleoyl chloride-papain (OC-PAP) conjugate that was synthesized via an amide bond formation between the acyl halide groups of oleoyl chloride and the amino group of papain. Prior to adding in the SEDDS formulation, the newly synthesized conjugate was evaluated quantitatively by a Bradford assay that demonstrated 45 µg of papain contents per mg of the conjugate. Moreover, the conjugate formation was qualitatively confirmed through FTIR analysis and thin layer chromatography. ACV (a BCS class III drug) was incorporated into the SEDDS formulations after being hydrophobically ion paired with sodium deoxycholate, thereby making it lipophilic. The drug-loaded formulations were emulsified in the 0.1 M phosphate buffer (pH 6.8) and evaluated in vitro with respect to drug release and rabbit mucosal permeation studies. Both the formulations illustrated a very comparable drug release over a period of 4 h, afterwards, the OC-PAP-based formulation demonstrated a more sustaining effect. The extent of mucus diffusion evaluated via the silicon tube method demonstrated a 4.92-fold and a 1.46-fold higher penetration of the drug, a 3.21-fold and a 1.56-fold higher permeation through the rabbit intestinal mucus layer, and a 22.94-fold and a 2.27-fold higher retention of the drug over the intact mucosa of rabbit intestine, illustrated by OC-PAP-based nanoemulsions compared to the drug-free solution and controlled nanoemulsion, respectively. According to these in vitro results, papain-functionalized SEDDS is a promising approach for the oral delivery of ACV and many other drugs with oral bioavailability issues, however, in vivo studies in this respect have to be employed before making a comprehensive conclusion. |
format | Online Article Text |
id | pubmed-9412565 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94125652022-08-27 Papain-Decorated Mucopenetrating SEDDS: A Tentative Approach to Combat Absorption Issues of Acyclovir via the Oral Route Mahmood, Arshad Haneef, Rabbia Al Meslamani, Ahmad Z. Bostanudin, Mohammad F. Sohail, Muhammad Sarfraz, Muhammad Arafat, Mosab Pharmaceutics Article The aim of the current study was to enhance the oral bioavailability of Acyclovir (ACV) based on the papain-functionalized self-emulsifying drug delivery systems (SEDDS). The optimum control SEDDS formulation comprised of kolliphore (40%), transcutol (30%), propylene glycol (20%) and oleoyl chloride (10%). However, in the targeted SEDDS formulation, oleoyl chloride was replaced with oleoyl chloride-papain (OC-PAP) conjugate that was synthesized via an amide bond formation between the acyl halide groups of oleoyl chloride and the amino group of papain. Prior to adding in the SEDDS formulation, the newly synthesized conjugate was evaluated quantitatively by a Bradford assay that demonstrated 45 µg of papain contents per mg of the conjugate. Moreover, the conjugate formation was qualitatively confirmed through FTIR analysis and thin layer chromatography. ACV (a BCS class III drug) was incorporated into the SEDDS formulations after being hydrophobically ion paired with sodium deoxycholate, thereby making it lipophilic. The drug-loaded formulations were emulsified in the 0.1 M phosphate buffer (pH 6.8) and evaluated in vitro with respect to drug release and rabbit mucosal permeation studies. Both the formulations illustrated a very comparable drug release over a period of 4 h, afterwards, the OC-PAP-based formulation demonstrated a more sustaining effect. The extent of mucus diffusion evaluated via the silicon tube method demonstrated a 4.92-fold and a 1.46-fold higher penetration of the drug, a 3.21-fold and a 1.56-fold higher permeation through the rabbit intestinal mucus layer, and a 22.94-fold and a 2.27-fold higher retention of the drug over the intact mucosa of rabbit intestine, illustrated by OC-PAP-based nanoemulsions compared to the drug-free solution and controlled nanoemulsion, respectively. According to these in vitro results, papain-functionalized SEDDS is a promising approach for the oral delivery of ACV and many other drugs with oral bioavailability issues, however, in vivo studies in this respect have to be employed before making a comprehensive conclusion. MDPI 2022-07-29 /pmc/articles/PMC9412565/ /pubmed/36015210 http://dx.doi.org/10.3390/pharmaceutics14081584 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mahmood, Arshad Haneef, Rabbia Al Meslamani, Ahmad Z. Bostanudin, Mohammad F. Sohail, Muhammad Sarfraz, Muhammad Arafat, Mosab Papain-Decorated Mucopenetrating SEDDS: A Tentative Approach to Combat Absorption Issues of Acyclovir via the Oral Route |
title | Papain-Decorated Mucopenetrating SEDDS: A Tentative Approach to Combat Absorption Issues of Acyclovir via the Oral Route |
title_full | Papain-Decorated Mucopenetrating SEDDS: A Tentative Approach to Combat Absorption Issues of Acyclovir via the Oral Route |
title_fullStr | Papain-Decorated Mucopenetrating SEDDS: A Tentative Approach to Combat Absorption Issues of Acyclovir via the Oral Route |
title_full_unstemmed | Papain-Decorated Mucopenetrating SEDDS: A Tentative Approach to Combat Absorption Issues of Acyclovir via the Oral Route |
title_short | Papain-Decorated Mucopenetrating SEDDS: A Tentative Approach to Combat Absorption Issues of Acyclovir via the Oral Route |
title_sort | papain-decorated mucopenetrating sedds: a tentative approach to combat absorption issues of acyclovir via the oral route |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9412565/ https://www.ncbi.nlm.nih.gov/pubmed/36015210 http://dx.doi.org/10.3390/pharmaceutics14081584 |
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