Drug-Eluting Biodegradable Implants for the Sustained Release of <i>Bis</i>phosphonates
Despite being one of the first-line treatments for osteoporosis, the <i>bis</i>phosphonate drug class exhibits an extremely low oral bioavailability (<1%) due to poor absorption from the gastrointestinal tract. To overcome this, and to explore the potential for sustained drug release,...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Polymers |
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| Online Access: | https://www.mdpi.com/2073-4360/12/12/2930 |
| _version_ | 1797545436346580992 |
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| author | Cintya Dharmayanti Todd A. Gillam Desmond B. Williams Anton Blencowe |
| author_facet | Cintya Dharmayanti Todd A. Gillam Desmond B. Williams Anton Blencowe |
| author_sort | Cintya Dharmayanti |
| collection | DOAJ |
| description | Despite being one of the first-line treatments for osteoporosis, the <i>bis</i>phosphonate drug class exhibits an extremely low oral bioavailability (<1%) due to poor absorption from the gastrointestinal tract. To overcome this, and to explore the potential for sustained drug release, bioerodible poly(lactic acid) (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) implants loaded with the <i>bis</i>phosphonate alendronate sodium (ALN) were prepared via hot-melt extrusion. The rate of drug release in vitro was modulated by tailoring the ratio of lactide to glycolide in the polymer and by altering the ALN-loading of the implants. All investigated implants exhibited sustained ALN release in vitro between 25 to 130 days, where implants of greater glycolide composition and higher ALN-loadings released ALN more rapidly. All PLGA implants demonstrated a sigmoidal release profile, characterised by an initial surface dissolution phase, followed by a period of zero-order drug diffusion, then relaxation or erosion of the polymer chains that caused accelerated release over the subsequent days. Contrastingly, the PLA implants demonstrated a logarithmic release profile, characterised by a gradual decrease in ALN release over time. |
| first_indexed | 2024-03-10T14:16:22Z |
| format | Article |
| id | doaj.art-39585942bab04c889fb9b8176f9bbcc2 |
| institution | Directory Open Access Journal |
| issn | 2073-4360 |
| language | English |
| last_indexed | 2024-03-10T14:16:22Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Polymers |
| spelling | doaj.art-39585942bab04c889fb9b8176f9bbcc22023-11-20T23:46:33ZengMDPI AGPolymers2073-43602020-12-011212293010.3390/polym12122930Drug-Eluting Biodegradable Implants for the Sustained Release of <i>Bis</i>phosphonatesCintya Dharmayanti0Todd A. Gillam1Desmond B. Williams2Anton Blencowe3Applied Chemistry and Translational Biomaterials Group, Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaApplied Chemistry and Translational Biomaterials Group, Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaPharmacy and Biomedical Sciences, Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaApplied Chemistry and Translational Biomaterials Group, Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, AustraliaDespite being one of the first-line treatments for osteoporosis, the <i>bis</i>phosphonate drug class exhibits an extremely low oral bioavailability (<1%) due to poor absorption from the gastrointestinal tract. To overcome this, and to explore the potential for sustained drug release, bioerodible poly(lactic acid) (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) implants loaded with the <i>bis</i>phosphonate alendronate sodium (ALN) were prepared via hot-melt extrusion. The rate of drug release in vitro was modulated by tailoring the ratio of lactide to glycolide in the polymer and by altering the ALN-loading of the implants. All investigated implants exhibited sustained ALN release in vitro between 25 to 130 days, where implants of greater glycolide composition and higher ALN-loadings released ALN more rapidly. All PLGA implants demonstrated a sigmoidal release profile, characterised by an initial surface dissolution phase, followed by a period of zero-order drug diffusion, then relaxation or erosion of the polymer chains that caused accelerated release over the subsequent days. Contrastingly, the PLA implants demonstrated a logarithmic release profile, characterised by a gradual decrease in ALN release over time.https://www.mdpi.com/2073-4360/12/12/2930<i>bis</i>phosphonateimplantosteoporosissustained releasepoly(lactic acid) (PLA)poly(D,L-lactide-<i>co</i>-glycolide) (PLGA) |
| spellingShingle | Cintya Dharmayanti Todd A. Gillam Desmond B. Williams Anton Blencowe Drug-Eluting Biodegradable Implants for the Sustained Release of <i>Bis</i>phosphonates Polymers <i>bis</i>phosphonate implant osteoporosis sustained release poly(lactic acid) (PLA) poly(D,L-lactide-<i>co</i>-glycolide) (PLGA) |
| title | Drug-Eluting Biodegradable Implants for the Sustained Release of <i>Bis</i>phosphonates |
| title_full | Drug-Eluting Biodegradable Implants for the Sustained Release of <i>Bis</i>phosphonates |
| title_fullStr | Drug-Eluting Biodegradable Implants for the Sustained Release of <i>Bis</i>phosphonates |
| title_full_unstemmed | Drug-Eluting Biodegradable Implants for the Sustained Release of <i>Bis</i>phosphonates |
| title_short | Drug-Eluting Biodegradable Implants for the Sustained Release of <i>Bis</i>phosphonates |
| title_sort | drug eluting biodegradable implants for the sustained release of i bis i phosphonates |
| topic | <i>bis</i>phosphonate implant osteoporosis sustained release poly(lactic acid) (PLA) poly(D,L-lactide-<i>co</i>-glycolide) (PLGA) |
| url | https://www.mdpi.com/2073-4360/12/12/2930 |
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