| 1. |
- Abramson, Alex, et al.
(författare)
-
A luminal unfolding microneedle injector for oral delivery of macromolecules
- 2019
-
Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:10, s. 1512-
-
Tidskriftsartikel (refereegranskat)abstract
- Insulin and other injectable biologic drugs have transformed the treatment of patients suffering from diabetes(1,2), yet patients and healthcare providers often prefer to use and prescribe less effective orally dosed medications(3-5). Compared with subcutaneously administered drugs, oral formulations create less patient discomfort(4), show greater chemical stability at high temperatures(6), and do not generate biohazardous needle waste(7). An oral dosage form for biologic medications is ideal; however, macromolecule drugs are not readily absorbed into the bloodstream through the gastrointestinal tract(8). We developed an ingestible capsule, termed the luminal unfolding microneedle injector, which allows for the oral delivery of biologic drugs by rapidly propelling dissolvable drug-loaded microneedles into intestinal tissue using a set of unfolding arms. During ex vivo human and in vivo swine studies, the device consistently delivered the microneedles to the tissue without causing complete thickness perforations. Using insulin as a model drug, we showed that, when actuated, the luminal unfolding microneedle injector provided a faster pharmacokinetic uptake profile and a systemic uptake > 10% of that of a subcutaneous injection over a 4-h sampling period. With the ability to load a multitude of microneedle formulations, the device can serve as a platform to orally deliver therapeutic doses of macromolecule drugs.
|
|
| 2. |
- Caffarel-Salvador, Ester, et al.
(författare)
-
A microneedle platform for buccal macromolecule delivery
- 2021
-
Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:4
-
Tidskriftsartikel (refereegranskat)abstract
- Alternative means for drug delivery are needed to facilitate drug adherence and administration. Microneedles (MNs) have been previously investigated transdermally for drug delivery. To date, drug loading into MNs has been limited by drug solubility in the polymeric blend. We designed a highly drug-loaded MN patch to deliver macromolecules and applied it to the buccal area, which allows for faster delivery than the skin. We successfully delivered 1-mg payloads of human insulin and human growth hormone to the buccal cavity of swine within 30 s. In addition, we conducted a trial in 100 healthy volunteers to assess potential discomfort associated with MNs when applied in the oral cavity, identifying the hard palate as the preferred application site. We envisage that MN patches applied on buccal surfaces could increase medication adherence and facilitate the painless delivery of biologics and other drugs to many, especially for the pediatric and elderly populations.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Verma, Malvika, et al.
(författare)
-
A gastric resident drug delivery system for prolonged gram-level dosing of tuberculosis treatment
- 2019
-
Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 11:483
-
Tidskriftsartikel (refereegranskat)abstract
- Multigram drug depot systems for extended drug release could transform our capacity to effectively treat patients across a myriad of diseases. For example, tuberculosis (TB) requires multimonth courses of daily multigram doses for treatment. To address the challenge of prolonged dosing for regimens requiring multigram drug dosing, we developed a gastric resident system delivered through the nasogastric route that was capable of safely encapsulating and releasing grams of antibiotics over a period of weeks. Initial preclinical safety and drug release were demonstrated in a swine model with a panel of TB antibiotics. We anticipate multiple applications in the field of infectious diseases, as well as for other indications where multigram depots could impart meaningful benefits to patients, helping maximize adherence to their medication.
|
|
