Microneedle-Mediated Transdermal Delivery of Bevacizumab
| Autor: | Kathryn McAvoy, Helen O. McCarthy, Maelíosa T.C. McCrudden, Aaron J. Courtenay, Ryan F. Donnelly |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Swine Transdermal Patch Pharmaceutical Science 02 engineering and technology Pharmacology Rats Sprague-Dawley microneedle Antineoplastic Agents Immunological Drug Delivery Systems dissolving Neoplasms Drug Discovery Tissue Distribution Skin Transdermal Hydrogels 021001 nanoscience & nanotechnology Bevacizumab medicine.anatomical_structure Molecular Medicine Female Lymph 0210 nano-technology medicine.drug Microinjections Skin Absorption Cmax Biological Availability bevacizumab Administration Cutaneous 03 medical and health sciences Pharmacokinetics SDG 3 - Good Health and Well-being In vivo medicine Stratum corneum Animals hydrogel-forming business.industry Rats Bioavailability 030104 developmental biology transdermal business |
| Zdroj: | Courtenay, A J, McCrudden, M T C, McAvoy, K J, McCarthy, H O & Donnelly, R F 2018, ' Microneedle-Mediated Transdermal Delivery of Bevacizumab ', Molecular Pharmaceutics, vol. 15, no. 8, pp. 3545-3556 . https://doi.org/10.1021/acs.molpharmaceut.8b00544 |
| DOI: | 10.1021/acs.molpharmaceut.8b00544 |
| Popis: | Bevacizumab is a recombinant humanized monoclonal antibody used clinically as a combination chemotherapeutic. Antibody therapeutics are usually formulated as parenteral injections, owing to their low oral bioavailability. Microneedle technology provides a transdermal alternative for drug-delivery using micron-scale needle structures to penetrate directly through the stratum corneum into the dermal interstitium. This study describes the design, formulation, and in vitro characterization of both dissolving and hydrogel-forming microneedle array platforms for transdermal delivery of bevacizumab. Bevacizumab recovery and transdermal permeation studies were conducted and analyzed using bevacizumab specific ELISA. Prototype microneedle-patches were tested in vivo in Sprague-Dawley rats with serum, exterior lumbar and axial lymph nodes, spleen, and skin tissue concentrations of bevacizumab reported. This work represents the first example of high dose transdermal delivery of an antibody therapeutic in vivo using dissolving and hydrogel-forming microneedle platforms. Basic pharmacokinetic parameters are described including hydrogel-forming microneedles: Cmax 358.2 ± 100.4 ng/mL, Tmax 48 h, AUC 44357 ± 4540, and Css 942 ± 95 ng/mL, highlighting the potential for these devices to provide sustained delivery of antibody therapeutics to the lymph and systemic circulation. Targeted delivery of chemotherapeutic agents to the lymphatic system by MN technology may provide new treatment options for cancer metastases. |
| Databáze: | OpenAIRE |
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