Controlling the burst release of amorphous drug–polysaccharide nanoparticle complex via crosslinking of the polysaccharide chains
High-payload amorphous drug–polysaccharide nanoparticle complex (or nanoplex in short) represents a new class of supersaturating drug delivery systems intended for bioavailability enhancement of poorly-soluble drugs. Not unlike other nanoscale amorphous formulations, the nanoplex exhibits fast disso...
| Main Authors: | , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
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2016
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| Online Access: | https://hdl.handle.net/10356/82276 http://hdl.handle.net/10220/41174 |
| _version_ | 1811686350246641664 |
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| author | Nguyen, Minh-Hiep Tran, The-Thien Hadinoto, Kunn |
| author2 | School of Chemical and Biomedical Engineering |
| author_facet | School of Chemical and Biomedical Engineering Nguyen, Minh-Hiep Tran, The-Thien Hadinoto, Kunn |
| author_sort | Nguyen, Minh-Hiep |
| collection | NTU |
| description | High-payload amorphous drug–polysaccharide nanoparticle complex (or nanoplex in short) represents a new class of supersaturating drug delivery systems intended for bioavailability enhancement of poorly-soluble drugs. Not unlike other nanoscale amorphous formulations, the nanoplex exhibits fast dissolution characterized by a burst drug release pattern. While the burst release is ideal for supersaturation generation in the presence of crystallization inhibitor, it is not as ideal for passive targeting drug delivery applications in which the nanoplex must be delivered by itself. Herein we developed nanoplex exhibiting controlled release via crosslinking of the polysaccharide chains onto which the drug molecules were electrostatically bound to. Curcumin and chitosan were used, respectively, as the drug and polysaccharide models with amine-reactive disuccinimidyl tartrate as the crosslinking agent. The crosslinked nanoplex exhibited improved morphology (i.e. smaller size, more spherical, and higher uniformity) that signified its more condensed structure. A twenty-fold reduction in the initial burst release rate with a threefold reduction in the overall dissolution rate was obtained after crosslinking. The slower dissolution was attributed to the more condensed structure of the crosslinked nanoplex that enhanced its dissociation stability in phosphate buffered saline. The reduction in the dissolution rate was proportional to the degree of crosslinking that was governed by the crosslinker to amine ratio. The crosslinking caused slight reductions in the payload and zeta potential of the nanoplex, but with no adverse effect on the cytotoxicity. This proof-of-concept study successfully demonstrated the use of polysaccharide crosslinking to control the drug release from high-payload amorphous drug nanoplex. |
| first_indexed | 2024-10-01T04:59:01Z |
| format | Journal Article |
| id | ntu-10356/82276 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:59:01Z |
| publishDate | 2016 |
| record_format | dspace |
| spelling | ntu-10356/822762023-12-29T06:48:32Z Controlling the burst release of amorphous drug–polysaccharide nanoparticle complex via crosslinking of the polysaccharide chains Nguyen, Minh-Hiep Tran, The-Thien Hadinoto, Kunn School of Chemical and Biomedical Engineering Amorphization Drug–polysaccharide complex High-payload amorphous drug–polysaccharide nanoparticle complex (or nanoplex in short) represents a new class of supersaturating drug delivery systems intended for bioavailability enhancement of poorly-soluble drugs. Not unlike other nanoscale amorphous formulations, the nanoplex exhibits fast dissolution characterized by a burst drug release pattern. While the burst release is ideal for supersaturation generation in the presence of crystallization inhibitor, it is not as ideal for passive targeting drug delivery applications in which the nanoplex must be delivered by itself. Herein we developed nanoplex exhibiting controlled release via crosslinking of the polysaccharide chains onto which the drug molecules were electrostatically bound to. Curcumin and chitosan were used, respectively, as the drug and polysaccharide models with amine-reactive disuccinimidyl tartrate as the crosslinking agent. The crosslinked nanoplex exhibited improved morphology (i.e. smaller size, more spherical, and higher uniformity) that signified its more condensed structure. A twenty-fold reduction in the initial burst release rate with a threefold reduction in the overall dissolution rate was obtained after crosslinking. The slower dissolution was attributed to the more condensed structure of the crosslinked nanoplex that enhanced its dissociation stability in phosphate buffered saline. The reduction in the dissolution rate was proportional to the degree of crosslinking that was governed by the crosslinker to amine ratio. The crosslinking caused slight reductions in the payload and zeta potential of the nanoplex, but with no adverse effect on the cytotoxicity. This proof-of-concept study successfully demonstrated the use of polysaccharide crosslinking to control the drug release from high-payload amorphous drug nanoplex. Accepted version 2016-08-25T08:44:39Z 2019-12-06T14:52:19Z 2016-08-25T08:44:39Z 2019-12-06T14:52:19Z 2016 Journal Article Nguyen, M.-H., Tran, T.-T., & Hadinoto, K. (2016). Controlling the burst release of amorphous drug–polysaccharide nanoparticle complex via crosslinking of the polysaccharide chains. European Journal of Pharmaceutics and Biopharmaceutics, 104, 156-163. 0939-6411 https://hdl.handle.net/10356/82276 http://hdl.handle.net/10220/41174 10.1016/j.ejpb.2016.05.006 en European Journal of Pharmaceutics and Biopharmaceutics © 2016 Elsevier. This is the author created version of a work that has been peer reviewed and accepted for publication by European Journal of Pharmaceutics and Biopharmaceutics, Elsevier. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: [http://dx.doi.org/10.1016/j.ejpb.2016.05.006]. 26 p. application/pdf |
| spellingShingle | Amorphization Drug–polysaccharide complex Nguyen, Minh-Hiep Tran, The-Thien Hadinoto, Kunn Controlling the burst release of amorphous drug–polysaccharide nanoparticle complex via crosslinking of the polysaccharide chains |
| title | Controlling the burst release of amorphous drug–polysaccharide nanoparticle complex via crosslinking of the polysaccharide chains |
| title_full | Controlling the burst release of amorphous drug–polysaccharide nanoparticle complex via crosslinking of the polysaccharide chains |
| title_fullStr | Controlling the burst release of amorphous drug–polysaccharide nanoparticle complex via crosslinking of the polysaccharide chains |
| title_full_unstemmed | Controlling the burst release of amorphous drug–polysaccharide nanoparticle complex via crosslinking of the polysaccharide chains |
| title_short | Controlling the burst release of amorphous drug–polysaccharide nanoparticle complex via crosslinking of the polysaccharide chains |
| title_sort | controlling the burst release of amorphous drug polysaccharide nanoparticle complex via crosslinking of the polysaccharide chains |
| topic | Amorphization Drug–polysaccharide complex |
| url | https://hdl.handle.net/10356/82276 http://hdl.handle.net/10220/41174 |
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