Cargando…

Design of Mucoadhesive Nanostructured Polyelectrolyte Complexes Based on Chitosan and Hypromellose Phthalate for Metronidazole Delivery Intended to the Treatment of Helicobacter pylori Infections

Metronidazole (MT) is an important drug available for Helicobacter pylori infection treatment. However, in the past few years, this drug has presented effective reduction for infection control, one of the most important reasons is attributed to the reduction of retention time in the stomach environm...

Descripción completa

Detalles Bibliográficos
Autores principales: Chaves de Souza, Maurício Palmeira, de Mattos, Nathalia Helena, Pedreiro, Liliane Neves, Boni, Fernanda Isadora, dos Santos Ramos, Matheus Aparecido, Bauab, Taís Maria, Gremião, Maria Palmira Daflon, Chorilli, Marlus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765050/
https://www.ncbi.nlm.nih.gov/pubmed/33327588
http://dx.doi.org/10.3390/pharmaceutics12121211
_version_ 1783628400589537280
author Chaves de Souza, Maurício Palmeira
de Mattos, Nathalia Helena
Pedreiro, Liliane Neves
Boni, Fernanda Isadora
dos Santos Ramos, Matheus Aparecido
Bauab, Taís Maria
Gremião, Maria Palmira Daflon
Chorilli, Marlus
author_facet Chaves de Souza, Maurício Palmeira
de Mattos, Nathalia Helena
Pedreiro, Liliane Neves
Boni, Fernanda Isadora
dos Santos Ramos, Matheus Aparecido
Bauab, Taís Maria
Gremião, Maria Palmira Daflon
Chorilli, Marlus
author_sort Chaves de Souza, Maurício Palmeira
collection PubMed
description Metronidazole (MT) is an important drug available for Helicobacter pylori infection treatment. However, in the past few years, this drug has presented effective reduction for infection control, one of the most important reasons is attributed to the reduction of retention time in the stomach environment. Mucoadhesive nanostructured polyelectrolyte complexes (nano PECs) based on chitosan (CS) and hypromellose phthalate (HP) were rationally developed using a full factorial design (2(1) × 2(1) × 3(1)), for the incorporation of MT based on the enhancement of the antimicrobial potential against active Helicobacter pylori, in the stomach. Different mass ratios of CS:HP (w/w) were tested, reaching the most promising ratios of 1:0.1, 1:0.5, and 1:1, and two methods of polymers addition (pouring-I and drip-II) were also evaluated. From method I, the obtained particles presented a diameter in the range of 811–1293 nm (Z-average) and a polydispersity index (PDI) between 0.47 and 0.88. By method II, there was a significant reduction in diameter and PDI to 553–739 nm and 0.23 at 0.34, respectively. The drug incorporation also resulted in a reduction in the diameter and PDI of the nano PECs. All samples showed positive zeta potential, about 20 mV, and a high percentage of MT incorporation (±95%). The method factor presented a greater influence on the nano PECs characteristics. Interactions in the system constituents were indicated by the FTIR data. Nano PECs mucoadhesiveness was observed and the composition and charge density were responsible for this phenomenon. MT dissolution evaluation showed the similarity of the dissolution profiles of free and loaded MT, in which almost 100% of the drug was in the simulated gastric medium in 120 min of testing. The in vitro antimicrobial potential against H. pylori of loaded nano PECs were measured and the minimum inhibitory concentration observed for free MT was >2000 µg/mL, while for the incorporated MT lower values were observed, showing an increase in the encapsulated MT activity.
format Online
Article
Text
id pubmed-7765050
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-77650502020-12-27 Design of Mucoadhesive Nanostructured Polyelectrolyte Complexes Based on Chitosan and Hypromellose Phthalate for Metronidazole Delivery Intended to the Treatment of Helicobacter pylori Infections Chaves de Souza, Maurício Palmeira de Mattos, Nathalia Helena Pedreiro, Liliane Neves Boni, Fernanda Isadora dos Santos Ramos, Matheus Aparecido Bauab, Taís Maria Gremião, Maria Palmira Daflon Chorilli, Marlus Pharmaceutics Article Metronidazole (MT) is an important drug available for Helicobacter pylori infection treatment. However, in the past few years, this drug has presented effective reduction for infection control, one of the most important reasons is attributed to the reduction of retention time in the stomach environment. Mucoadhesive nanostructured polyelectrolyte complexes (nano PECs) based on chitosan (CS) and hypromellose phthalate (HP) were rationally developed using a full factorial design (2(1) × 2(1) × 3(1)), for the incorporation of MT based on the enhancement of the antimicrobial potential against active Helicobacter pylori, in the stomach. Different mass ratios of CS:HP (w/w) were tested, reaching the most promising ratios of 1:0.1, 1:0.5, and 1:1, and two methods of polymers addition (pouring-I and drip-II) were also evaluated. From method I, the obtained particles presented a diameter in the range of 811–1293 nm (Z-average) and a polydispersity index (PDI) between 0.47 and 0.88. By method II, there was a significant reduction in diameter and PDI to 553–739 nm and 0.23 at 0.34, respectively. The drug incorporation also resulted in a reduction in the diameter and PDI of the nano PECs. All samples showed positive zeta potential, about 20 mV, and a high percentage of MT incorporation (±95%). The method factor presented a greater influence on the nano PECs characteristics. Interactions in the system constituents were indicated by the FTIR data. Nano PECs mucoadhesiveness was observed and the composition and charge density were responsible for this phenomenon. MT dissolution evaluation showed the similarity of the dissolution profiles of free and loaded MT, in which almost 100% of the drug was in the simulated gastric medium in 120 min of testing. The in vitro antimicrobial potential against H. pylori of loaded nano PECs were measured and the minimum inhibitory concentration observed for free MT was >2000 µg/mL, while for the incorporated MT lower values were observed, showing an increase in the encapsulated MT activity. MDPI 2020-12-14 /pmc/articles/PMC7765050/ /pubmed/33327588 http://dx.doi.org/10.3390/pharmaceutics12121211 Text en © 2020 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 Article
Chaves de Souza, Maurício Palmeira
de Mattos, Nathalia Helena
Pedreiro, Liliane Neves
Boni, Fernanda Isadora
dos Santos Ramos, Matheus Aparecido
Bauab, Taís Maria
Gremião, Maria Palmira Daflon
Chorilli, Marlus
Design of Mucoadhesive Nanostructured Polyelectrolyte Complexes Based on Chitosan and Hypromellose Phthalate for Metronidazole Delivery Intended to the Treatment of Helicobacter pylori Infections
title Design of Mucoadhesive Nanostructured Polyelectrolyte Complexes Based on Chitosan and Hypromellose Phthalate for Metronidazole Delivery Intended to the Treatment of Helicobacter pylori Infections
title_full Design of Mucoadhesive Nanostructured Polyelectrolyte Complexes Based on Chitosan and Hypromellose Phthalate for Metronidazole Delivery Intended to the Treatment of Helicobacter pylori Infections
title_fullStr Design of Mucoadhesive Nanostructured Polyelectrolyte Complexes Based on Chitosan and Hypromellose Phthalate for Metronidazole Delivery Intended to the Treatment of Helicobacter pylori Infections
title_full_unstemmed Design of Mucoadhesive Nanostructured Polyelectrolyte Complexes Based on Chitosan and Hypromellose Phthalate for Metronidazole Delivery Intended to the Treatment of Helicobacter pylori Infections
title_short Design of Mucoadhesive Nanostructured Polyelectrolyte Complexes Based on Chitosan and Hypromellose Phthalate for Metronidazole Delivery Intended to the Treatment of Helicobacter pylori Infections
title_sort design of mucoadhesive nanostructured polyelectrolyte complexes based on chitosan and hypromellose phthalate for metronidazole delivery intended to the treatment of helicobacter pylori infections
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765050/
https://www.ncbi.nlm.nih.gov/pubmed/33327588
http://dx.doi.org/10.3390/pharmaceutics12121211
work_keys_str_mv AT chavesdesouzamauriciopalmeira designofmucoadhesivenanostructuredpolyelectrolytecomplexesbasedonchitosanandhypromellosephthalateformetronidazoledeliveryintendedtothetreatmentofhelicobacterpyloriinfections
AT demattosnathaliahelena designofmucoadhesivenanostructuredpolyelectrolytecomplexesbasedonchitosanandhypromellosephthalateformetronidazoledeliveryintendedtothetreatmentofhelicobacterpyloriinfections
AT pedreirolilianeneves designofmucoadhesivenanostructuredpolyelectrolytecomplexesbasedonchitosanandhypromellosephthalateformetronidazoledeliveryintendedtothetreatmentofhelicobacterpyloriinfections
AT bonifernandaisadora designofmucoadhesivenanostructuredpolyelectrolytecomplexesbasedonchitosanandhypromellosephthalateformetronidazoledeliveryintendedtothetreatmentofhelicobacterpyloriinfections
AT dossantosramosmatheusaparecido designofmucoadhesivenanostructuredpolyelectrolytecomplexesbasedonchitosanandhypromellosephthalateformetronidazoledeliveryintendedtothetreatmentofhelicobacterpyloriinfections
AT bauabtaismaria designofmucoadhesivenanostructuredpolyelectrolytecomplexesbasedonchitosanandhypromellosephthalateformetronidazoledeliveryintendedtothetreatmentofhelicobacterpyloriinfections
AT gremiaomariapalmiradaflon designofmucoadhesivenanostructuredpolyelectrolytecomplexesbasedonchitosanandhypromellosephthalateformetronidazoledeliveryintendedtothetreatmentofhelicobacterpyloriinfections
AT chorillimarlus designofmucoadhesivenanostructuredpolyelectrolytecomplexesbasedonchitosanandhypromellosephthalateformetronidazoledeliveryintendedtothetreatmentofhelicobacterpyloriinfections