Development, in vitro and ex vivo characterization of lamotrigine-loaded bovine serum albumin nanoparticles using QbD approach
The present study aimed to prepare and optimize lamotrigine-loaded bovine serum albumin nanoparticles (LAM-NP) using the Quality by Design (QbD) approach and to investigate both the in vitro and ex vivo effects of different cross-linking agents glutaraldehyde (GLUT), glucose (GLUC) and 1-(3-dimethyl...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Drug Delivery |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/10717544.2025.2460693 |
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| author | Maryana Salamah Bence Sipos Zsuzsanna Schelz István Zupkó Ágnes Kiricsi Ágnes Szalenkó-Tőkés László Rovó Gábor Katona György Tibor Balogh Ildikó Csóka |
| author_facet | Maryana Salamah Bence Sipos Zsuzsanna Schelz István Zupkó Ágnes Kiricsi Ágnes Szalenkó-Tőkés László Rovó Gábor Katona György Tibor Balogh Ildikó Csóka |
| author_sort | Maryana Salamah |
| collection | DOAJ |
| description | The present study aimed to prepare and optimize lamotrigine-loaded bovine serum albumin nanoparticles (LAM-NP) using the Quality by Design (QbD) approach and to investigate both the in vitro and ex vivo effects of different cross-linking agents glutaraldehyde (GLUT), glucose (GLUC) and 1-(3-dimethylaminutesopropyl)-3-ethylcarbodiimide hydrochloride (EDC) on intranasal applicability. Cross-linked LAM-NP from EDC (NP-EDC-1) showed the lowest Z-average value (163.7 ± 1.9 nm) and drug encapsulation efficacy (EE%) of 97.31 ± 0.17%. The drug release of GLUC cross-linked LAM-NP (NP-GLUC-9), glutaraldehyde cross-linked LAM-NP (NP-GLUT-2), and NP-EDC-1 at blood circulation conditions was higher than the initial LAM. The results of the blood-brain barrier parallel artificial membrane permeability assay (BBB-PAMPA) showed an increase in the permeability of LAM through the BBB with NP-GLUC-9 and an increase in flux with all selected formulations. The ex vivo study showed that LAM diffusion from the selected formulations through the human nasal mucosa was higher than in case of initial LAM. The cytotoxicity study indicated that BSA-NP reduced LAM toxicity, and GLUC 9 mM and EDC 1 mg could be alternative cross-linking agents to avoid GLUT 2% v/v toxicity. Furthermore, permeability through Caco-2 cells showed that nasal epithelial transport/absorption of LAM was improved by using BSA-NPs. The use of BSA-NP may be a promising approach to enhance the solubility, permeability through BBB and decrease the frequency of dosing and adverse effects of LAM. |
| format | Article |
| id | doaj-art-42ce790163fe43e5a3985b0fd1dd461a |
| institution | Kabale University |
| issn | 1071-7544 1521-0464 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Drug Delivery |
| spelling | doaj-art-42ce790163fe43e5a3985b0fd1dd461a2025-02-04T05:06:16ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642025-12-0132110.1080/10717544.2025.2460693Development, in vitro and ex vivo characterization of lamotrigine-loaded bovine serum albumin nanoparticles using QbD approachMaryana Salamah0Bence Sipos1Zsuzsanna Schelz2István Zupkó3Ágnes Kiricsi4Ágnes Szalenkó-Tőkés5László Rovó6Gábor Katona7György Tibor Balogh8Ildikó Csóka9Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Szeged, HungaryInstitute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Szeged, HungaryInstitute of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, HungaryInstitute of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Szeged, HungaryDepartment of Oto-Rhino-Laryngology and Head-Neck Surgery, University of Szeged, Szeged, HungaryDepartment of Oto-Rhino-Laryngology and Head-Neck Surgery, University of Szeged, Szeged, HungaryDepartment of Oto-Rhino-Laryngology and Head-Neck Surgery, University of Szeged, Szeged, HungaryInstitute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Szeged, HungaryDepartment of Pharmaceutical Chemistry, Semmelweis University, Budapest, HungaryInstitute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Szeged, HungaryThe present study aimed to prepare and optimize lamotrigine-loaded bovine serum albumin nanoparticles (LAM-NP) using the Quality by Design (QbD) approach and to investigate both the in vitro and ex vivo effects of different cross-linking agents glutaraldehyde (GLUT), glucose (GLUC) and 1-(3-dimethylaminutesopropyl)-3-ethylcarbodiimide hydrochloride (EDC) on intranasal applicability. Cross-linked LAM-NP from EDC (NP-EDC-1) showed the lowest Z-average value (163.7 ± 1.9 nm) and drug encapsulation efficacy (EE%) of 97.31 ± 0.17%. The drug release of GLUC cross-linked LAM-NP (NP-GLUC-9), glutaraldehyde cross-linked LAM-NP (NP-GLUT-2), and NP-EDC-1 at blood circulation conditions was higher than the initial LAM. The results of the blood-brain barrier parallel artificial membrane permeability assay (BBB-PAMPA) showed an increase in the permeability of LAM through the BBB with NP-GLUC-9 and an increase in flux with all selected formulations. The ex vivo study showed that LAM diffusion from the selected formulations through the human nasal mucosa was higher than in case of initial LAM. The cytotoxicity study indicated that BSA-NP reduced LAM toxicity, and GLUC 9 mM and EDC 1 mg could be alternative cross-linking agents to avoid GLUT 2% v/v toxicity. Furthermore, permeability through Caco-2 cells showed that nasal epithelial transport/absorption of LAM was improved by using BSA-NPs. The use of BSA-NP may be a promising approach to enhance the solubility, permeability through BBB and decrease the frequency of dosing and adverse effects of LAM.https://www.tandfonline.com/doi/10.1080/10717544.2025.2460693Lamotriginebovine serum albumincross-linkingnanoparticlesquality by designnasal delivery |
| spellingShingle | Maryana Salamah Bence Sipos Zsuzsanna Schelz István Zupkó Ágnes Kiricsi Ágnes Szalenkó-Tőkés László Rovó Gábor Katona György Tibor Balogh Ildikó Csóka Development, in vitro and ex vivo characterization of lamotrigine-loaded bovine serum albumin nanoparticles using QbD approach Drug Delivery Lamotrigine bovine serum albumin cross-linking nanoparticles quality by design nasal delivery |
| title | Development, in vitro and ex vivo characterization of lamotrigine-loaded bovine serum albumin nanoparticles using QbD approach |
| title_full | Development, in vitro and ex vivo characterization of lamotrigine-loaded bovine serum albumin nanoparticles using QbD approach |
| title_fullStr | Development, in vitro and ex vivo characterization of lamotrigine-loaded bovine serum albumin nanoparticles using QbD approach |
| title_full_unstemmed | Development, in vitro and ex vivo characterization of lamotrigine-loaded bovine serum albumin nanoparticles using QbD approach |
| title_short | Development, in vitro and ex vivo characterization of lamotrigine-loaded bovine serum albumin nanoparticles using QbD approach |
| title_sort | development in vitro and ex vivo characterization of lamotrigine loaded bovine serum albumin nanoparticles using qbd approach |
| topic | Lamotrigine bovine serum albumin cross-linking nanoparticles quality by design nasal delivery |
| url | https://www.tandfonline.com/doi/10.1080/10717544.2025.2460693 |
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