Self-assembled insulin and nanogels polyelectrolyte complex (Ins/NGs-PEC) for oral insulin delivery: characterization, lyophilization and in-vivo evaluation
Jahanzeb Mudassir1,2, Yusrida Darwis,1 Suriani Muhamad,1 Arshad Ali Khan1,31Discipline of Pharmaceutical Technology, School of Pharmaceutical Sciences, Universiti Sains, Malaysia, 11800, Penang Malaysia; 2Department of Pharmaceutics, Faculty of Pharmacy, Bahanuddin Zakariya, Multan, Pakistan; 3Facul...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-07-01
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| Series: | International Journal of Nanomedicine |
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| Online Access: | https://www.dovepress.com/self-assembled-insulin-and-nanogels-polyelectrolyte-complex-insngs-pec-peer-reviewed-article-IJN |
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| author | Mudassir J Darwis Y Muhamad S Khan AA |
| author_facet | Mudassir J Darwis Y Muhamad S Khan AA |
| author_sort | Mudassir J |
| collection | DOAJ |
| description | Jahanzeb Mudassir1,2, Yusrida Darwis,1 Suriani Muhamad,1 Arshad Ali Khan1,31Discipline of Pharmaceutical Technology, School of Pharmaceutical Sciences, Universiti Sains, Malaysia, 11800, Penang Malaysia; 2Department of Pharmaceutics, Faculty of Pharmacy, Bahanuddin Zakariya, Multan, Pakistan; 3Faculty of Engineering Technology, Universiti Malaysia Pahang, Kuantan, Pahang, MalaysiaIntroduction: Insulin is given by injection, because when administered orally, it would be destroyed by enzymes in the digestive system, hence only about 0.1% reaches blood circulation. The purpose of the present study was to use pH sensitive polyelectrolyte methyl methacrylate (MMA)/itaconic acid (IA) nanogels as carriers in an attempt to improve absorption of insulin administered orally.Methods: Insulin (Ins) was incorporated into the MMA/IA nanogels (NGs) using the polyelectrolyte complexation (PEC) method to form Ins/NGs-PEC. Several parameters, including Ins:NGs ratio, pH, incubation time and stirring rate were optimized during preparation of InsNGs-PEC. The prepared formulations were characterized in terms of particle size (PS), polydispersity index (PdI), zeta potential (ZP) and percent entrapment efficiency (% EE).Results: The optimized InF12 nanogels had a PS, PdI, ZP and %EE of 190.43 nm, 0.186, −16.70 mV and 85.20%, respectively. The InF12 nanogels were lyophilized in the presence of different concentrations of trehalose as cryoprotectant. The lyophilized InF12 containing 2%w/v trahalose (InF12-Tre2 nanogels) was chosen as final formulation which had a PS, PdI, ZP and %EE of 430.50 nm, 0.588, −16.50 mv and 82.10, respectively. The in vitro release of insulin from InF12-Tre2 nanogels in the SGF and SIF were 28.71% and 96.53%, respectively. The stability study conducted at 5±3°C for 3 months showed that lnF12-Tre2 nanogels were stable. The SDS-PAGE assay indicated that the primary structure of insulin in the lnF12-Tre2 nanogels was intact. The in-vivo study in the diabetic rats following oral administration of InF12-Tre2 nanogels at a dose of 100 IU/kg body weight reduced blood glucose level significantly to 51.10% after 6 hours compared to the control groups.Conclusions: The pH sensitive MMA/IA nanogels are potential carriers for oral delivery of insulin as they enhanced the absorption of the drug.Keywords: acrylic monomers, peptides self assembly, lyophilization, hypoglycemic effect, polymeric nanogels |
| first_indexed | 2024-12-19T08:51:02Z |
| format | Article |
| id | doaj.art-45170065504c4022aea2b8f595474e3a |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-12-19T08:51:02Z |
| publishDate | 2019-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-45170065504c4022aea2b8f595474e3a2022-12-21T20:28:43ZengDove Medical PressInternational Journal of Nanomedicine1178-20132019-07-01Volume 144895490946896Self-assembled insulin and nanogels polyelectrolyte complex (Ins/NGs-PEC) for oral insulin delivery: characterization, lyophilization and in-vivo evaluationMudassir JDarwis YMuhamad SKhan AAJahanzeb Mudassir1,2, Yusrida Darwis,1 Suriani Muhamad,1 Arshad Ali Khan1,31Discipline of Pharmaceutical Technology, School of Pharmaceutical Sciences, Universiti Sains, Malaysia, 11800, Penang Malaysia; 2Department of Pharmaceutics, Faculty of Pharmacy, Bahanuddin Zakariya, Multan, Pakistan; 3Faculty of Engineering Technology, Universiti Malaysia Pahang, Kuantan, Pahang, MalaysiaIntroduction: Insulin is given by injection, because when administered orally, it would be destroyed by enzymes in the digestive system, hence only about 0.1% reaches blood circulation. The purpose of the present study was to use pH sensitive polyelectrolyte methyl methacrylate (MMA)/itaconic acid (IA) nanogels as carriers in an attempt to improve absorption of insulin administered orally.Methods: Insulin (Ins) was incorporated into the MMA/IA nanogels (NGs) using the polyelectrolyte complexation (PEC) method to form Ins/NGs-PEC. Several parameters, including Ins:NGs ratio, pH, incubation time and stirring rate were optimized during preparation of InsNGs-PEC. The prepared formulations were characterized in terms of particle size (PS), polydispersity index (PdI), zeta potential (ZP) and percent entrapment efficiency (% EE).Results: The optimized InF12 nanogels had a PS, PdI, ZP and %EE of 190.43 nm, 0.186, −16.70 mV and 85.20%, respectively. The InF12 nanogels were lyophilized in the presence of different concentrations of trehalose as cryoprotectant. The lyophilized InF12 containing 2%w/v trahalose (InF12-Tre2 nanogels) was chosen as final formulation which had a PS, PdI, ZP and %EE of 430.50 nm, 0.588, −16.50 mv and 82.10, respectively. The in vitro release of insulin from InF12-Tre2 nanogels in the SGF and SIF were 28.71% and 96.53%, respectively. The stability study conducted at 5±3°C for 3 months showed that lnF12-Tre2 nanogels were stable. The SDS-PAGE assay indicated that the primary structure of insulin in the lnF12-Tre2 nanogels was intact. The in-vivo study in the diabetic rats following oral administration of InF12-Tre2 nanogels at a dose of 100 IU/kg body weight reduced blood glucose level significantly to 51.10% after 6 hours compared to the control groups.Conclusions: The pH sensitive MMA/IA nanogels are potential carriers for oral delivery of insulin as they enhanced the absorption of the drug.Keywords: acrylic monomers, peptides self assembly, lyophilization, hypoglycemic effect, polymeric nanogelshttps://www.dovepress.com/self-assembled-insulin-and-nanogels-polyelectrolyte-complex-insngs-pec-peer-reviewed-article-IJNacrylic monomerspeptides self assemblylyophilizationhypoglycemic effectpolymeric nanogels |
| spellingShingle | Mudassir J Darwis Y Muhamad S Khan AA Self-assembled insulin and nanogels polyelectrolyte complex (Ins/NGs-PEC) for oral insulin delivery: characterization, lyophilization and in-vivo evaluation International Journal of Nanomedicine acrylic monomers peptides self assembly lyophilization hypoglycemic effect polymeric nanogels |
| title | Self-assembled insulin and nanogels polyelectrolyte complex (Ins/NGs-PEC) for oral insulin delivery: characterization, lyophilization and in-vivo evaluation |
| title_full | Self-assembled insulin and nanogels polyelectrolyte complex (Ins/NGs-PEC) for oral insulin delivery: characterization, lyophilization and in-vivo evaluation |
| title_fullStr | Self-assembled insulin and nanogels polyelectrolyte complex (Ins/NGs-PEC) for oral insulin delivery: characterization, lyophilization and in-vivo evaluation |
| title_full_unstemmed | Self-assembled insulin and nanogels polyelectrolyte complex (Ins/NGs-PEC) for oral insulin delivery: characterization, lyophilization and in-vivo evaluation |
| title_short | Self-assembled insulin and nanogels polyelectrolyte complex (Ins/NGs-PEC) for oral insulin delivery: characterization, lyophilization and in-vivo evaluation |
| title_sort | self assembled insulin and nanogels polyelectrolyte complex ins ngs pec for oral insulin delivery characterization lyophilization and in vivo evaluation |
| topic | acrylic monomers peptides self assembly lyophilization hypoglycemic effect polymeric nanogels |
| url | https://www.dovepress.com/self-assembled-insulin-and-nanogels-polyelectrolyte-complex-insngs-pec-peer-reviewed-article-IJN |
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