Design of Mucoadhesive Nanostructured Polyelectrolyte Complexes Based on Chitosan and Hypromellose Phthalate for Metronidazole Delivery Intended to the Treatment of <i>Helicobacter pylori</i> Infections
Metronidazole (MT) is an important drug available for <i>Helicobacter pylori</i> 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 t...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/12/12/1211 |
| _version_ | 1797544774140428288 |
|---|---|
| author | Maurício Palmeira Chaves de Souza Nathalia Helena de Mattos Liliane Neves Pedreiro Fernanda Isadora Boni Matheus Aparecido dos Santos Ramos Taís Maria Bauab Maria Palmira Daflon Gremião Marlus Chorilli |
| author_facet | Maurício Palmeira Chaves de Souza Nathalia Helena de Mattos Liliane Neves Pedreiro Fernanda Isadora Boni Matheus Aparecido dos Santos Ramos Taís Maria Bauab Maria Palmira Daflon Gremião Marlus Chorilli |
| author_sort | Maurício Palmeira Chaves de Souza |
| collection | DOAJ |
| description | Metronidazole (MT) is an important drug available for <i>Helicobacter pylori</i> 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<sup>1</sup> × 2<sup>1</sup> × 3<sup>1</sup>), for the incorporation of MT based on the enhancement of the antimicrobial potential against active <i>Helicobacter pylori</i>, in the stomach. Different mass ratios of CS:HP (<i>w/w</i>) 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 <i>H. pylori</i> 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. |
| first_indexed | 2024-03-10T14:05:13Z |
| format | Article |
| id | doaj.art-b93f00584fd44cffb053da402619be15 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T14:05:13Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-b93f00584fd44cffb053da402619be152023-11-21T00:46:36ZengMDPI AGPharmaceutics1999-49232020-12-011212121110.3390/pharmaceutics12121211Design of Mucoadhesive Nanostructured Polyelectrolyte Complexes Based on Chitosan and Hypromellose Phthalate for Metronidazole Delivery Intended to the Treatment of <i>Helicobacter pylori</i> InfectionsMaurício Palmeira Chaves de Souza0Nathalia Helena de Mattos1Liliane Neves Pedreiro2Fernanda Isadora Boni3Matheus Aparecido dos Santos Ramos4Taís Maria Bauab5Maria Palmira Daflon Gremião6Marlus Chorilli7Department of Drug and Medicines, School of Pharmaceutical Sciences, Campus Araraquara, São Paulo State University (UNESP), Araraquara-SP, Road Araraquara-Jaú, Km 01, 14.800-903 São Paulo, BrazilDepartment of Drug and Medicines, School of Pharmaceutical Sciences, Campus Araraquara, São Paulo State University (UNESP), Araraquara-SP, Road Araraquara-Jaú, Km 01, 14.800-903 São Paulo, BrazilDepartment of Drug and Medicines, School of Pharmaceutical Sciences, Campus Araraquara, São Paulo State University (UNESP), Araraquara-SP, Road Araraquara-Jaú, Km 01, 14.800-903 São Paulo, BrazilDepartment of Drug and Medicines, School of Pharmaceutical Sciences, Campus Araraquara, São Paulo State University (UNESP), Araraquara-SP, Road Araraquara-Jaú, Km 01, 14.800-903 São Paulo, BrazilDepartment of Biological Sciences, School of Pharmaceutical Sciences, Campus Araraquara, São Paulo State University (UNESP), 14.800-903 São Paulo, BrazilDepartment of Biological Sciences, School of Pharmaceutical Sciences, Campus Araraquara, São Paulo State University (UNESP), 14.800-903 São Paulo, BrazilDepartment of Drug and Medicines, School of Pharmaceutical Sciences, Campus Araraquara, São Paulo State University (UNESP), Araraquara-SP, Road Araraquara-Jaú, Km 01, 14.800-903 São Paulo, BrazilDepartment of Drug and Medicines, School of Pharmaceutical Sciences, Campus Araraquara, São Paulo State University (UNESP), Araraquara-SP, Road Araraquara-Jaú, Km 01, 14.800-903 São Paulo, BrazilMetronidazole (MT) is an important drug available for <i>Helicobacter pylori</i> 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<sup>1</sup> × 2<sup>1</sup> × 3<sup>1</sup>), for the incorporation of MT based on the enhancement of the antimicrobial potential against active <i>Helicobacter pylori</i>, in the stomach. Different mass ratios of CS:HP (<i>w/w</i>) 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 <i>H. pylori</i> 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.https://www.mdpi.com/1999-4923/12/12/1211mucoadhesive nanostructured polyelectrolyte complexes (nano PECs)chitosandesign of experimentsadsorption isothermsin vitro dissolution test |
| spellingShingle | Maurício Palmeira Chaves de Souza Nathalia Helena de Mattos Liliane Neves Pedreiro Fernanda Isadora Boni Matheus Aparecido dos Santos Ramos Taís Maria Bauab Maria Palmira Daflon Gremião Marlus Chorilli Design of Mucoadhesive Nanostructured Polyelectrolyte Complexes Based on Chitosan and Hypromellose Phthalate for Metronidazole Delivery Intended to the Treatment of <i>Helicobacter pylori</i> Infections Pharmaceutics mucoadhesive nanostructured polyelectrolyte complexes (nano PECs) chitosan design of experiments adsorption isotherms in vitro dissolution test |
| title | Design of Mucoadhesive Nanostructured Polyelectrolyte Complexes Based on Chitosan and Hypromellose Phthalate for Metronidazole Delivery Intended to the Treatment of <i>Helicobacter pylori</i> Infections |
| title_full | Design of Mucoadhesive Nanostructured Polyelectrolyte Complexes Based on Chitosan and Hypromellose Phthalate for Metronidazole Delivery Intended to the Treatment of <i>Helicobacter pylori</i> Infections |
| title_fullStr | Design of Mucoadhesive Nanostructured Polyelectrolyte Complexes Based on Chitosan and Hypromellose Phthalate for Metronidazole Delivery Intended to the Treatment of <i>Helicobacter pylori</i> Infections |
| title_full_unstemmed | Design of Mucoadhesive Nanostructured Polyelectrolyte Complexes Based on Chitosan and Hypromellose Phthalate for Metronidazole Delivery Intended to the Treatment of <i>Helicobacter pylori</i> Infections |
| title_short | Design of Mucoadhesive Nanostructured Polyelectrolyte Complexes Based on Chitosan and Hypromellose Phthalate for Metronidazole Delivery Intended to the Treatment of <i>Helicobacter pylori</i> Infections |
| title_sort | design of mucoadhesive nanostructured polyelectrolyte complexes based on chitosan and hypromellose phthalate for metronidazole delivery intended to the treatment of i helicobacter pylori i infections |
| topic | mucoadhesive nanostructured polyelectrolyte complexes (nano PECs) chitosan design of experiments adsorption isotherms in vitro dissolution test |
| url | https://www.mdpi.com/1999-4923/12/12/1211 |
| work_keys_str_mv | AT mauriciopalmeirachavesdesouza designofmucoadhesivenanostructuredpolyelectrolytecomplexesbasedonchitosanandhypromellosephthalateformetronidazoledeliveryintendedtothetreatmentofihelicobacterpyloriiinfections AT nathaliahelenademattos designofmucoadhesivenanostructuredpolyelectrolytecomplexesbasedonchitosanandhypromellosephthalateformetronidazoledeliveryintendedtothetreatmentofihelicobacterpyloriiinfections AT lilianenevespedreiro designofmucoadhesivenanostructuredpolyelectrolytecomplexesbasedonchitosanandhypromellosephthalateformetronidazoledeliveryintendedtothetreatmentofihelicobacterpyloriiinfections AT fernandaisadoraboni designofmucoadhesivenanostructuredpolyelectrolytecomplexesbasedonchitosanandhypromellosephthalateformetronidazoledeliveryintendedtothetreatmentofihelicobacterpyloriiinfections AT matheusaparecidodossantosramos designofmucoadhesivenanostructuredpolyelectrolytecomplexesbasedonchitosanandhypromellosephthalateformetronidazoledeliveryintendedtothetreatmentofihelicobacterpyloriiinfections AT taismariabauab designofmucoadhesivenanostructuredpolyelectrolytecomplexesbasedonchitosanandhypromellosephthalateformetronidazoledeliveryintendedtothetreatmentofihelicobacterpyloriiinfections AT mariapalmiradaflongremiao designofmucoadhesivenanostructuredpolyelectrolytecomplexesbasedonchitosanandhypromellosephthalateformetronidazoledeliveryintendedtothetreatmentofihelicobacterpyloriiinfections AT marluschorilli designofmucoadhesivenanostructuredpolyelectrolytecomplexesbasedonchitosanandhypromellosephthalateformetronidazoledeliveryintendedtothetreatmentofihelicobacterpyloriiinfections |