A lipid-based delivery platform for pulsatile delivery of teriparatide Article Swipe
Corinna Schlosser
,
Wojciech Rozek
,
Ryan Mellor
,
Szymon W. Manka
,
Christopher M. Morris
,
Steve Brocchini
,
Gareth R. Williams
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.26434/chemrxiv-2024-1sxfh
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.26434/chemrxiv-2024-1sxfh
Teriparatide (and analogue peptides) are the only FDA approved anabolic treatments for osteoporosis. Current therapies are administered as a daily subcutaneous injection, which limits patient adherence and clinical efficacy. To achieve the desired anabolic effect, a controlled delivery system must ensure a pulsatile release profile over a prolonged period. Thermo-responsive formulations (e.g. liposomes) can undergo a temperature-related phase-transition which can allow active control of drug release. Herein, thermo-responsive liposomes were developed to permit precise control over the teriparatide release rate through modulation of temperature. Entrapment of hydrophilic molecules, including peptides within liposomes remains challenging due to the large volume of hydration. In this work, hydrophobic ion pairing was employed for the first time to enhance peptide entrapment within liposomes. The method resulted in a hydrophobic complex that achieved high teriparatide entrapment (>75%) in sub-200 nm, monodispersed liposomes. Hydrophobic ion pairing outperformed other entrapment approaches. Several liposomal formulations with transition temperatures between 38 – 50 °C were obtained by modulation of the phospholipid composition. In vitro release assays demonstrated temperature-dependent release kinetics with faster rates of release observed at/above the transition temperature. The maintenance of biological activity of released teriparatide was demonstrated in a cell-based assay utilising the PTH1R receptor. Overall, this provides the first proof-of-concept of the suitability of thermo-responsive systems for pulsatile delivery of teriparatide and similar peptides.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- http://doi.org/10.26434/chemrxiv-2024-1sxfh
- OA Status
- gold
- Cited By
- 1
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4402378054
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4402378054Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.26434/chemrxiv-2024-1sxfhDigital Object Identifier
- Title
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A lipid-based delivery platform for pulsatile delivery of teriparatideWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2024Year of publication
- Publication date
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2024-09-09Full publication date if available
- Authors
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Corinna Schlosser, Wojciech Rozek, Ryan Mellor, Szymon W. Manka, Christopher M. Morris, Steve Brocchini, Gareth R. WilliamsList of authors in order
- Landing page
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https://doi.org/10.26434/chemrxiv-2024-1sxfhPublisher landing page
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://doi.org/10.26434/chemrxiv-2024-1sxfhDirect OA link when available
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Teriparatide, Pulsatile flow, Delivery system, Drug delivery, Computer science, Chemistry, Nanotechnology, Biomedical engineering, Medicine, Internal medicine, Materials science, Osteoporosis, Bone mineralTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
1Total citation count in OpenAlex
- Citations by year (recent)
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2024: 1Per-year citation counts (last 5 years)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.ion | 105, 138 |
| abstract_inverted_index.nm, | 134 |
| abstract_inverted_index.the | 5, 31, 76, 96, 110, 160, 178, 196, 202, 206 |
| abstract_inverted_index.was | 107, 189 |
| abstract_inverted_index.°C | 154 |
| abstract_inverted_index.– | 152 |
| abstract_inverted_index.(and | 1 |
| abstract_inverted_index.drug | 64 |
| abstract_inverted_index.high | 128 |
| abstract_inverted_index.must | 39 |
| abstract_inverted_index.only | 6 |
| abstract_inverted_index.over | 45, 75 |
| abstract_inverted_index.rate | 79 |
| abstract_inverted_index.that | 126 |
| abstract_inverted_index.this | 102, 200 |
| abstract_inverted_index.time | 112 |
| abstract_inverted_index.were | 69, 155 |
| abstract_inverted_index.with | 147, 171 |
| abstract_inverted_index.(e.g. | 51 |
| abstract_inverted_index.PTH1R | 197 |
| abstract_inverted_index.allow | 60 |
| abstract_inverted_index.assay | 194 |
| abstract_inverted_index.daily | 19 |
| abstract_inverted_index.first | 111, 203 |
| abstract_inverted_index.large | 97 |
| abstract_inverted_index.other | 141 |
| abstract_inverted_index.rates | 173 |
| abstract_inverted_index.vitro | 164 |
| abstract_inverted_index.which | 22, 58 |
| abstract_inverted_index.work, | 103 |
| abstract_inverted_index.active | 61 |
| abstract_inverted_index.assays | 166 |
| abstract_inverted_index.ensure | 40 |
| abstract_inverted_index.faster | 172 |
| abstract_inverted_index.limits | 23 |
| abstract_inverted_index.method | 120 |
| abstract_inverted_index.permit | 72 |
| abstract_inverted_index.system | 38 |
| abstract_inverted_index.volume | 98 |
| abstract_inverted_index.within | 90, 117 |
| abstract_inverted_index.Current | 13 |
| abstract_inverted_index.Herein, | 66 |
| abstract_inverted_index.Several | 144 |
| abstract_inverted_index.achieve | 30 |
| abstract_inverted_index.between | 150 |
| abstract_inverted_index.complex | 125 |
| abstract_inverted_index.control | 62, 74 |
| abstract_inverted_index.desired | 32 |
| abstract_inverted_index.effect, | 34 |
| abstract_inverted_index.enhance | 114 |
| abstract_inverted_index.pairing | 106, 139 |
| abstract_inverted_index.patient | 24 |
| abstract_inverted_index.peptide | 115 |
| abstract_inverted_index.period. | 48 |
| abstract_inverted_index.precise | 73 |
| abstract_inverted_index.profile | 44 |
| abstract_inverted_index.release | 43, 78, 165, 169, 175 |
| abstract_inverted_index.remains | 92 |
| abstract_inverted_index.similar | 217 |
| abstract_inverted_index.sub-200 | 133 |
| abstract_inverted_index.systems | 210 |
| abstract_inverted_index.through | 80 |
| abstract_inverted_index.undergo | 54 |
| abstract_inverted_index.Overall, | 199 |
| abstract_inverted_index.achieved | 127 |
| abstract_inverted_index.activity | 185 |
| abstract_inverted_index.anabolic | 9, 33 |
| abstract_inverted_index.analogue | 2 |
| abstract_inverted_index.approved | 8 |
| abstract_inverted_index.at/above | 177 |
| abstract_inverted_index.clinical | 27 |
| abstract_inverted_index.delivery | 37, 213 |
| abstract_inverted_index.employed | 108 |
| abstract_inverted_index.kinetics | 170 |
| abstract_inverted_index.observed | 176 |
| abstract_inverted_index.obtained | 156 |
| abstract_inverted_index.peptides | 89 |
| abstract_inverted_index.provides | 201 |
| abstract_inverted_index.release. | 65 |
| abstract_inverted_index.released | 187 |
| abstract_inverted_index.resulted | 121 |
| abstract_inverted_index.(>75%) | 131 |
| abstract_inverted_index.adherence | 25 |
| abstract_inverted_index.developed | 70 |
| abstract_inverted_index.efficacy. | 28 |
| abstract_inverted_index.including | 88 |
| abstract_inverted_index.liposomal | 145 |
| abstract_inverted_index.liposomes | 68, 91 |
| abstract_inverted_index.peptides) | 3 |
| abstract_inverted_index.peptides. | 218 |
| abstract_inverted_index.prolonged | 47 |
| abstract_inverted_index.pulsatile | 42, 212 |
| abstract_inverted_index.receptor. | 198 |
| abstract_inverted_index.therapies | 14 |
| abstract_inverted_index.utilising | 195 |
| abstract_inverted_index.Entrapment | 84 |
| abstract_inverted_index.biological | 184 |
| abstract_inverted_index.cell-based | 193 |
| abstract_inverted_index.controlled | 36 |
| abstract_inverted_index.entrapment | 116, 130, 142 |
| abstract_inverted_index.hydration. | 100 |
| abstract_inverted_index.injection, | 21 |
| abstract_inverted_index.liposomes) | 52 |
| abstract_inverted_index.liposomes. | 118, 136 |
| abstract_inverted_index.modulation | 81, 158 |
| abstract_inverted_index.molecules, | 87 |
| abstract_inverted_index.transition | 148, 179 |
| abstract_inverted_index.treatments | 10 |
| abstract_inverted_index.Hydrophobic | 137 |
| abstract_inverted_index.approaches. | 143 |
| abstract_inverted_index.challenging | 93 |
| abstract_inverted_index.hydrophilic | 86 |
| abstract_inverted_index.hydrophobic | 104, 124 |
| abstract_inverted_index.maintenance | 182 |
| abstract_inverted_index.suitability | 207 |
| abstract_inverted_index.Teriparatide | 0 |
| abstract_inverted_index.administered | 16 |
| abstract_inverted_index.composition. | 162 |
| abstract_inverted_index.demonstrated | 167, 190 |
| abstract_inverted_index.formulations | 50, 146 |
| abstract_inverted_index.outperformed | 140 |
| abstract_inverted_index.phospholipid | 161 |
| abstract_inverted_index.subcutaneous | 20 |
| abstract_inverted_index.temperature. | 83, 180 |
| abstract_inverted_index.temperatures | 149 |
| abstract_inverted_index.teriparatide | 77, 129, 188, 215 |
| abstract_inverted_index.monodispersed | 135 |
| abstract_inverted_index.osteoporosis. | 12 |
| abstract_inverted_index.phase-transition | 57 |
| abstract_inverted_index.proof-of-concept | 204 |
| abstract_inverted_index.Thermo-responsive | 49 |
| abstract_inverted_index.thermo-responsive | 67, 209 |
| abstract_inverted_index.temperature-related | 56 |
| abstract_inverted_index.temperature-dependent | 168 |
| cited_by_percentile_year.max | 94 |
| cited_by_percentile_year.min | 90 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 7 |
| citation_normalized_percentile.value | 0.53799806 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |