Hydroxyethylcellulose-Based Hydrogels Containing Liposomes Functionalized with Cell-Penetrating Peptides for Nasal Delivery of Insulin in the Treatment of Diabetes

Detalhes bibliográficos
Autor(a) principal: Von Zuben, Eliete de Souza [UNESP]
Data de Publicação: 2022
Outros Autores: Eloy, Josimar Oliveira, Inácio, Maiara Destro [UNESP], Araujo, Victor Hugo Sousa [UNESP], Baviera, Amanda Martins [UNESP], Gremião, Maria Palmira Daflon [UNESP], Chorilli, Marlus [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.3390/pharmaceutics14112492
http://hdl.handle.net/11449/248476
Resumo: Liposomes functionalized with cell-penetrating peptides are a promising strategy to deliver insulin through the nasal route. A hydrogel based on hydroxyethylcellulose (HEC) aqueous solution was prepared, followed by a subsequent addition of liposomes containing insulin solution functionalized with trans-activator of transcription protein of HIV-1 (TAT) or Penetratin (PNT). The formulations were characterized for rheological behavior, mucoadhesion, syringeability, in vitro release and in vivo efficacy. Rheological tests revealed non-Newtonian fluids with pseudoplastic behavior, and the incorporation of liposomes (HLI, HLITAT and HLIPNT) in hydrogels did not alter the behavior original pseudoplastic characteristic of the HEC hydrogel. Pseudoplastic flow behavior is a desirable property for formulations intended for the administration of drugs via the nasal route. The results of syringeability and mucoadhesive strength from HEC hydrogels suggest a viable vehicle for nasal delivery. Comparing the insulin release profile, it is observed that HI was the system that released the greatest amount while the liposomal gel promoted greater drug retention, since the liposomal system provides an extra barrier for the release through the hydrogel. Additionally, it is observed that both peptides tested had an impact on the insulin release profile, promoting a slower release, due to complexation with insulin. The in vitro release kinetics of insulin from all formulations followed Weibull’s mathematical model, reaching approximately 90% of release in the formulation prepared with HEC-based hydrogels. Serum insulin levels and the antihyperglycemic effects suggested that formulations HI and HLI have potential as carriers for insulin delivery by the nasal pathway, a profile not observed when insulin was administered by subcutaneous injection or by the nasal route in saline. Furthermore, formulations functionalized with TAT and PNT can be considered promoters of late and early absorption, respectively.
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spelling Hydroxyethylcellulose-Based Hydrogels Containing Liposomes Functionalized with Cell-Penetrating Peptides for Nasal Delivery of Insulin in the Treatment of Diabetesantihyperglycemic effectcell-penetrating peptidehydrogelinsulinliposomenasal deliveryLiposomes functionalized with cell-penetrating peptides are a promising strategy to deliver insulin through the nasal route. A hydrogel based on hydroxyethylcellulose (HEC) aqueous solution was prepared, followed by a subsequent addition of liposomes containing insulin solution functionalized with trans-activator of transcription protein of HIV-1 (TAT) or Penetratin (PNT). The formulations were characterized for rheological behavior, mucoadhesion, syringeability, in vitro release and in vivo efficacy. Rheological tests revealed non-Newtonian fluids with pseudoplastic behavior, and the incorporation of liposomes (HLI, HLITAT and HLIPNT) in hydrogels did not alter the behavior original pseudoplastic characteristic of the HEC hydrogel. Pseudoplastic flow behavior is a desirable property for formulations intended for the administration of drugs via the nasal route. The results of syringeability and mucoadhesive strength from HEC hydrogels suggest a viable vehicle for nasal delivery. Comparing the insulin release profile, it is observed that HI was the system that released the greatest amount while the liposomal gel promoted greater drug retention, since the liposomal system provides an extra barrier for the release through the hydrogel. Additionally, it is observed that both peptides tested had an impact on the insulin release profile, promoting a slower release, due to complexation with insulin. The in vitro release kinetics of insulin from all formulations followed Weibull’s mathematical model, reaching approximately 90% of release in the formulation prepared with HEC-based hydrogels. Serum insulin levels and the antihyperglycemic effects suggested that formulations HI and HLI have potential as carriers for insulin delivery by the nasal pathway, a profile not observed when insulin was administered by subcutaneous injection or by the nasal route in saline. Furthermore, formulations functionalized with TAT and PNT can be considered promoters of late and early absorption, respectively.Department of Drugs and Medicines School of Pharmaceutical Sciences São Paulo State University (UNESP), Rodovia Araraquara-Jaú, Km1Department of Pharmacy School of Pharmacy Dentistry and Nursing Federal University of CearáDepartment of Clinical Analysis School of Pharmaceutical Sciences São Paulo State University (UNESP), Rodovia Araraquara-Jaú, Km1Department of Drugs and Medicines School of Pharmaceutical Sciences São Paulo State University (UNESP), Rodovia Araraquara-Jaú, Km1Department of Clinical Analysis School of Pharmaceutical Sciences São Paulo State University (UNESP), Rodovia Araraquara-Jaú, Km1Universidade Estadual Paulista (UNESP)Federal University of CearáVon Zuben, Eliete de Souza [UNESP]Eloy, Josimar OliveiraInácio, Maiara Destro [UNESP]Araujo, Victor Hugo Sousa [UNESP]Baviera, Amanda Martins [UNESP]Gremião, Maria Palmira Daflon [UNESP]Chorilli, Marlus [UNESP]2023-07-29T13:45:05Z2023-07-29T13:45:05Z2022-11-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3390/pharmaceutics14112492Pharmaceutics, v. 14, n. 11, 2022.1999-4923http://hdl.handle.net/11449/24847610.3390/pharmaceutics141124922-s2.0-85149547463Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPharmaceuticsinfo:eu-repo/semantics/openAccess2023-07-29T13:45:05Zoai:repositorio.unesp.br:11449/248476Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-07-29T13:45:05Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Hydroxyethylcellulose-Based Hydrogels Containing Liposomes Functionalized with Cell-Penetrating Peptides for Nasal Delivery of Insulin in the Treatment of Diabetes
title Hydroxyethylcellulose-Based Hydrogels Containing Liposomes Functionalized with Cell-Penetrating Peptides for Nasal Delivery of Insulin in the Treatment of Diabetes
spellingShingle Hydroxyethylcellulose-Based Hydrogels Containing Liposomes Functionalized with Cell-Penetrating Peptides for Nasal Delivery of Insulin in the Treatment of Diabetes
Von Zuben, Eliete de Souza [UNESP]
antihyperglycemic effect
cell-penetrating peptide
hydrogel
insulin
liposome
nasal delivery
title_short Hydroxyethylcellulose-Based Hydrogels Containing Liposomes Functionalized with Cell-Penetrating Peptides for Nasal Delivery of Insulin in the Treatment of Diabetes
title_full Hydroxyethylcellulose-Based Hydrogels Containing Liposomes Functionalized with Cell-Penetrating Peptides for Nasal Delivery of Insulin in the Treatment of Diabetes
title_fullStr Hydroxyethylcellulose-Based Hydrogels Containing Liposomes Functionalized with Cell-Penetrating Peptides for Nasal Delivery of Insulin in the Treatment of Diabetes
title_full_unstemmed Hydroxyethylcellulose-Based Hydrogels Containing Liposomes Functionalized with Cell-Penetrating Peptides for Nasal Delivery of Insulin in the Treatment of Diabetes
title_sort Hydroxyethylcellulose-Based Hydrogels Containing Liposomes Functionalized with Cell-Penetrating Peptides for Nasal Delivery of Insulin in the Treatment of Diabetes
author Von Zuben, Eliete de Souza [UNESP]
author_facet Von Zuben, Eliete de Souza [UNESP]
Eloy, Josimar Oliveira
Inácio, Maiara Destro [UNESP]
Araujo, Victor Hugo Sousa [UNESP]
Baviera, Amanda Martins [UNESP]
Gremião, Maria Palmira Daflon [UNESP]
Chorilli, Marlus [UNESP]
author_role author
author2 Eloy, Josimar Oliveira
Inácio, Maiara Destro [UNESP]
Araujo, Victor Hugo Sousa [UNESP]
Baviera, Amanda Martins [UNESP]
Gremião, Maria Palmira Daflon [UNESP]
Chorilli, Marlus [UNESP]
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (UNESP)
Federal University of Ceará
dc.contributor.author.fl_str_mv Von Zuben, Eliete de Souza [UNESP]
Eloy, Josimar Oliveira
Inácio, Maiara Destro [UNESP]
Araujo, Victor Hugo Sousa [UNESP]
Baviera, Amanda Martins [UNESP]
Gremião, Maria Palmira Daflon [UNESP]
Chorilli, Marlus [UNESP]
dc.subject.por.fl_str_mv antihyperglycemic effect
cell-penetrating peptide
hydrogel
insulin
liposome
nasal delivery
topic antihyperglycemic effect
cell-penetrating peptide
hydrogel
insulin
liposome
nasal delivery
description Liposomes functionalized with cell-penetrating peptides are a promising strategy to deliver insulin through the nasal route. A hydrogel based on hydroxyethylcellulose (HEC) aqueous solution was prepared, followed by a subsequent addition of liposomes containing insulin solution functionalized with trans-activator of transcription protein of HIV-1 (TAT) or Penetratin (PNT). The formulations were characterized for rheological behavior, mucoadhesion, syringeability, in vitro release and in vivo efficacy. Rheological tests revealed non-Newtonian fluids with pseudoplastic behavior, and the incorporation of liposomes (HLI, HLITAT and HLIPNT) in hydrogels did not alter the behavior original pseudoplastic characteristic of the HEC hydrogel. Pseudoplastic flow behavior is a desirable property for formulations intended for the administration of drugs via the nasal route. The results of syringeability and mucoadhesive strength from HEC hydrogels suggest a viable vehicle for nasal delivery. Comparing the insulin release profile, it is observed that HI was the system that released the greatest amount while the liposomal gel promoted greater drug retention, since the liposomal system provides an extra barrier for the release through the hydrogel. Additionally, it is observed that both peptides tested had an impact on the insulin release profile, promoting a slower release, due to complexation with insulin. The in vitro release kinetics of insulin from all formulations followed Weibull’s mathematical model, reaching approximately 90% of release in the formulation prepared with HEC-based hydrogels. Serum insulin levels and the antihyperglycemic effects suggested that formulations HI and HLI have potential as carriers for insulin delivery by the nasal pathway, a profile not observed when insulin was administered by subcutaneous injection or by the nasal route in saline. Furthermore, formulations functionalized with TAT and PNT can be considered promoters of late and early absorption, respectively.
publishDate 2022
dc.date.none.fl_str_mv 2022-11-01
2023-07-29T13:45:05Z
2023-07-29T13:45:05Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.3390/pharmaceutics14112492
Pharmaceutics, v. 14, n. 11, 2022.
1999-4923
http://hdl.handle.net/11449/248476
10.3390/pharmaceutics14112492
2-s2.0-85149547463
url http://dx.doi.org/10.3390/pharmaceutics14112492
http://hdl.handle.net/11449/248476
identifier_str_mv Pharmaceutics, v. 14, n. 11, 2022.
1999-4923
10.3390/pharmaceutics14112492
2-s2.0-85149547463
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Pharmaceutics
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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