<i>Add Sugar to Chitosan:</i> Mucoadhesion and In Vitro Intestinal Permeability of Mannosylated Chitosan Nanocarriers
Crosslinked chitosan nanocarriers (140–160 nm) entrapping coumarin-6 (<i>λ<sub>ex/em</sub></i> = 455/508 nm) with or without surface mannosylation were synthesized and assessed for cytotoxicity, adherence and cellular uptake in Caco-2 cells, flux across Caco-2 monolayers, and...
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| Format: | Article |
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MDPI AG
2022-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/4/830 |
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| author | Sadaf Ejaz Bridget Hogg Delyan R. Hristov David J. Brayden Muhammad Imran Sourav Bhattacharjee |
| author_facet | Sadaf Ejaz Bridget Hogg Delyan R. Hristov David J. Brayden Muhammad Imran Sourav Bhattacharjee |
| author_sort | Sadaf Ejaz |
| collection | DOAJ |
| description | Crosslinked chitosan nanocarriers (140–160 nm) entrapping coumarin-6 (<i>λ<sub>ex/em</sub></i> = 455/508 nm) with or without surface mannosylation were synthesized and assessed for cytotoxicity, adherence and cellular uptake in Caco-2 cells, flux across Caco-2 monolayers, and mucoadhesion to porcine mucin. Mannosylated and non-mannosylated nanocarriers demonstrated biocompatibility with slow release of coumarin-6 at pH 6.8 and 7.4 over 24 h. Adherence of the non-mannosylated nanocarriers (50 and 150 µg/mL) to Caco-2 cells was ~10% over 24 h, whereas cellular uptake of 25–30% was noted at 4 h. The mannosylated nanocarriers showed a similar adherence to non-mannosylated nanocarriers after 24 h, but a lower cellular uptake (~20%) at 1 h, comparable uptake at 4 h, and a higher uptake (~25–30%) at 24 h. Overall, the nanocarriers did not affect the integrity of Caco-2 monolayers. Mannosylated nanocarriers elicited higher P<sub>app</sub> of 1.6 × 10<sup>−6</sup> cm/s (50 µg/mL) and 1.2 × 10<sup>−6</sup> (150 µg/mL) than the non-mannosylated ones: 9.8 × 10<sup>−7</sup> cm/s (50 µg/mL) and 1.0 × 10<sup>−6</sup> (150 µg/mL) after 2 h. Non-mannosylated chitosan nanocarriers elicited enhanced adhesion to porcine gut mucin <i>via</i> mucin-filled microchannels due to higher cationic charge density. These results underpin the importance of surface chemistry in the biological interactions of nanocarriers, while highlighting the role of surface hydrophilicity in mucopermeation due to mannosylation. |
| first_indexed | 2024-03-09T04:17:53Z |
| format | Article |
| id | doaj.art-4e48d9fb10b34c6ebe4f173173ae579c |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T04:17:53Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-4e48d9fb10b34c6ebe4f173173ae579c2023-12-03T13:50:41ZengMDPI AGPharmaceutics1999-49232022-04-0114483010.3390/pharmaceutics14040830<i>Add Sugar to Chitosan:</i> Mucoadhesion and In Vitro Intestinal Permeability of Mannosylated Chitosan NanocarriersSadaf Ejaz0Bridget Hogg1Delyan R. Hristov2David J. Brayden3Muhammad Imran4Sourav Bhattacharjee5Department of Biosciences, COMSATS University Islamabad (CUI), Park Road, Islamabad 45550, PakistanSchool of Veterinary Medicine, University College Dublin (UCD), Belfield, D04 W6F6 Dublin, IrelandSchool of Veterinary Medicine, University College Dublin (UCD), Belfield, D04 W6F6 Dublin, IrelandSchool of Veterinary Medicine, University College Dublin (UCD), Belfield, D04 W6F6 Dublin, IrelandDepartment of Biosciences, COMSATS University Islamabad (CUI), Park Road, Islamabad 45550, PakistanSchool of Veterinary Medicine, University College Dublin (UCD), Belfield, D04 W6F6 Dublin, IrelandCrosslinked chitosan nanocarriers (140–160 nm) entrapping coumarin-6 (<i>λ<sub>ex/em</sub></i> = 455/508 nm) with or without surface mannosylation were synthesized and assessed for cytotoxicity, adherence and cellular uptake in Caco-2 cells, flux across Caco-2 monolayers, and mucoadhesion to porcine mucin. Mannosylated and non-mannosylated nanocarriers demonstrated biocompatibility with slow release of coumarin-6 at pH 6.8 and 7.4 over 24 h. Adherence of the non-mannosylated nanocarriers (50 and 150 µg/mL) to Caco-2 cells was ~10% over 24 h, whereas cellular uptake of 25–30% was noted at 4 h. The mannosylated nanocarriers showed a similar adherence to non-mannosylated nanocarriers after 24 h, but a lower cellular uptake (~20%) at 1 h, comparable uptake at 4 h, and a higher uptake (~25–30%) at 24 h. Overall, the nanocarriers did not affect the integrity of Caco-2 monolayers. Mannosylated nanocarriers elicited higher P<sub>app</sub> of 1.6 × 10<sup>−6</sup> cm/s (50 µg/mL) and 1.2 × 10<sup>−6</sup> (150 µg/mL) than the non-mannosylated ones: 9.8 × 10<sup>−7</sup> cm/s (50 µg/mL) and 1.0 × 10<sup>−6</sup> (150 µg/mL) after 2 h. Non-mannosylated chitosan nanocarriers elicited enhanced adhesion to porcine gut mucin <i>via</i> mucin-filled microchannels due to higher cationic charge density. These results underpin the importance of surface chemistry in the biological interactions of nanocarriers, while highlighting the role of surface hydrophilicity in mucopermeation due to mannosylation.https://www.mdpi.com/1999-4923/14/4/830chitosan nanoparticlesmannosylationsurface functionalizationmucoadhesionsurface charge densitybioconjugation |
| spellingShingle | Sadaf Ejaz Bridget Hogg Delyan R. Hristov David J. Brayden Muhammad Imran Sourav Bhattacharjee <i>Add Sugar to Chitosan:</i> Mucoadhesion and In Vitro Intestinal Permeability of Mannosylated Chitosan Nanocarriers Pharmaceutics chitosan nanoparticles mannosylation surface functionalization mucoadhesion surface charge density bioconjugation |
| title | <i>Add Sugar to Chitosan:</i> Mucoadhesion and In Vitro Intestinal Permeability of Mannosylated Chitosan Nanocarriers |
| title_full | <i>Add Sugar to Chitosan:</i> Mucoadhesion and In Vitro Intestinal Permeability of Mannosylated Chitosan Nanocarriers |
| title_fullStr | <i>Add Sugar to Chitosan:</i> Mucoadhesion and In Vitro Intestinal Permeability of Mannosylated Chitosan Nanocarriers |
| title_full_unstemmed | <i>Add Sugar to Chitosan:</i> Mucoadhesion and In Vitro Intestinal Permeability of Mannosylated Chitosan Nanocarriers |
| title_short | <i>Add Sugar to Chitosan:</i> Mucoadhesion and In Vitro Intestinal Permeability of Mannosylated Chitosan Nanocarriers |
| title_sort | i add sugar to chitosan i mucoadhesion and in vitro intestinal permeability of mannosylated chitosan nanocarriers |
| topic | chitosan nanoparticles mannosylation surface functionalization mucoadhesion surface charge density bioconjugation |
| url | https://www.mdpi.com/1999-4923/14/4/830 |
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