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Drug Bioavailability Enhancing Agents of Natural Origin (Bioenhancers) that Modulate Drug Membrane Permeation and Pre-Systemic Metabolism
Many new chemical entities are discovered with high therapeutic potential, however, many of these compounds exhibit unfavorable pharmacokinetic properties due to poor solubility and/or poor membrane permeation characteristics. The latter is mainly due to the lipid-like barrier imposed by epithelial...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359194/ https://www.ncbi.nlm.nih.gov/pubmed/30654429 http://dx.doi.org/10.3390/pharmaceutics11010033 |
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author | Peterson, Bianca Weyers, Morné Steenekamp, Jan H. Steyn, Johan D. Gouws, Chrisna Hamman, Josias H. |
author_facet | Peterson, Bianca Weyers, Morné Steenekamp, Jan H. Steyn, Johan D. Gouws, Chrisna Hamman, Josias H. |
author_sort | Peterson, Bianca |
collection | PubMed |
description | Many new chemical entities are discovered with high therapeutic potential, however, many of these compounds exhibit unfavorable pharmacokinetic properties due to poor solubility and/or poor membrane permeation characteristics. The latter is mainly due to the lipid-like barrier imposed by epithelial mucosal layers, which have to be crossed by drug molecules in order to exert a therapeutic effect. Another barrier is the pre-systemic metabolic degradation of drug molecules, mainly by cytochrome P450 enzymes located in the intestinal enterocytes and liver hepatocytes. Although the nasal, buccal and pulmonary routes of administration avoid the first-pass effect, they are still dependent on absorption of drug molecules across the mucosal surfaces to achieve systemic drug delivery. Bioenhancers (drug absorption enhancers of natural origin) have been identified that can increase the quantity of unchanged drug that appears in the systemic blood circulation by means of modulating membrane permeation and/or pre-systemic metabolism. The aim of this paper is to provide an overview of natural bioenhancers and their main mechanisms of action for the nasal, buccal, pulmonary and oral routes of drug administration. Poorly bioavailable drugs such as large, hydrophilic therapeutics are often administered by injections. Bioenhancers may potentially be used to benefit patients by making systemic delivery of these poorly bioavailable drugs possible via alternative routes of administration (i.e., oral, nasal, buccal or pulmonary routes of administration) and may also reduce dosages of small molecular drugs and thereby reduce treatment costs. |
format | Online Article Text |
id | pubmed-6359194 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63591942019-02-14 Drug Bioavailability Enhancing Agents of Natural Origin (Bioenhancers) that Modulate Drug Membrane Permeation and Pre-Systemic Metabolism Peterson, Bianca Weyers, Morné Steenekamp, Jan H. Steyn, Johan D. Gouws, Chrisna Hamman, Josias H. Pharmaceutics Review Many new chemical entities are discovered with high therapeutic potential, however, many of these compounds exhibit unfavorable pharmacokinetic properties due to poor solubility and/or poor membrane permeation characteristics. The latter is mainly due to the lipid-like barrier imposed by epithelial mucosal layers, which have to be crossed by drug molecules in order to exert a therapeutic effect. Another barrier is the pre-systemic metabolic degradation of drug molecules, mainly by cytochrome P450 enzymes located in the intestinal enterocytes and liver hepatocytes. Although the nasal, buccal and pulmonary routes of administration avoid the first-pass effect, they are still dependent on absorption of drug molecules across the mucosal surfaces to achieve systemic drug delivery. Bioenhancers (drug absorption enhancers of natural origin) have been identified that can increase the quantity of unchanged drug that appears in the systemic blood circulation by means of modulating membrane permeation and/or pre-systemic metabolism. The aim of this paper is to provide an overview of natural bioenhancers and their main mechanisms of action for the nasal, buccal, pulmonary and oral routes of drug administration. Poorly bioavailable drugs such as large, hydrophilic therapeutics are often administered by injections. Bioenhancers may potentially be used to benefit patients by making systemic delivery of these poorly bioavailable drugs possible via alternative routes of administration (i.e., oral, nasal, buccal or pulmonary routes of administration) and may also reduce dosages of small molecular drugs and thereby reduce treatment costs. MDPI 2019-01-16 /pmc/articles/PMC6359194/ /pubmed/30654429 http://dx.doi.org/10.3390/pharmaceutics11010033 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Peterson, Bianca Weyers, Morné Steenekamp, Jan H. Steyn, Johan D. Gouws, Chrisna Hamman, Josias H. Drug Bioavailability Enhancing Agents of Natural Origin (Bioenhancers) that Modulate Drug Membrane Permeation and Pre-Systemic Metabolism |
title | Drug Bioavailability Enhancing Agents of Natural Origin (Bioenhancers) that Modulate Drug Membrane Permeation and Pre-Systemic Metabolism |
title_full | Drug Bioavailability Enhancing Agents of Natural Origin (Bioenhancers) that Modulate Drug Membrane Permeation and Pre-Systemic Metabolism |
title_fullStr | Drug Bioavailability Enhancing Agents of Natural Origin (Bioenhancers) that Modulate Drug Membrane Permeation and Pre-Systemic Metabolism |
title_full_unstemmed | Drug Bioavailability Enhancing Agents of Natural Origin (Bioenhancers) that Modulate Drug Membrane Permeation and Pre-Systemic Metabolism |
title_short | Drug Bioavailability Enhancing Agents of Natural Origin (Bioenhancers) that Modulate Drug Membrane Permeation and Pre-Systemic Metabolism |
title_sort | drug bioavailability enhancing agents of natural origin (bioenhancers) that modulate drug membrane permeation and pre-systemic metabolism |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359194/ https://www.ncbi.nlm.nih.gov/pubmed/30654429 http://dx.doi.org/10.3390/pharmaceutics11010033 |
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