Hydroxyethylcellulose-Based Hydrogels Containing Liposomes Functionalized with Cell-Penetrating Peptides for Nasal Delivery of Insulin in the Treatment of Diabetes
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , |
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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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 |
|
_version_ |
1799965189039194112 |