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RISS 인기검색어
- 검색키워드
- 저자 : Ryan F. Donnelly (검색결과 2 건)
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Microneedle-Mediated Transdermal Delivery of Bevacizumab
Courtenay, Aaron J.,McCrudden, Maelí,osa T. C.,McAvoy, Kathryn J.,McCarthy, Helen O.,Donnelly, Ryan F. American Chemical Society 2018 Molecular pharmaceutics Vol.15 No.8
<P>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 <I>stratum corneum</I> into the dermal interstitium. This study describes the design, formulation, and <I>in vitro</I> 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 <I>in vivo</I> 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 <I>in vivo</I> using dissolving and hydrogel-forming microneedle platforms. Basic pharmacokinetic parameters are described including hydrogel-forming microneedles: <I>C</I><SUB>max</SUB> 358.2 ± 100.4 ng/mL, <I>T</I><SUB>max</SUB> 48 h, AUC 44357 ± 4540, and <I>C</I><SUB>ss</SUB> 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.</P> [FIG OMISSION]</BR>
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Eneko Larrañeta,Juan Domínguez-Robles,Martha Coogan,Emma Heaney,Sarah A. Stewart,Raghu Raj Singh Thakur,Ryan F. Donnelly 한국고분자학회 2019 Macromolecular Research Vol.27 No.4
Hydrogels have been extensively investigated as a platform for drug delivery. However, their use for the delivery of hydrophobic drugs has been limited by their incompatibility with hydrophobic drug molecules. The chemical modification of the structure of the hydrogels to include hydrophobic moieties has been proven to be a good alternative to increase the stability and solubility of hydrophobic drugs in the polymer matrix of the hydrogel. The inclusion of hydroxypropyl-β-cyclodextrins (HPBCD) and Tween® 85 (T85) within hydrogel matrices has the potential to improve hydrophobic drug loading and release. HPBCD have the ability to host hydrophobic drug molecules in their cone-like structure, forming inclusion complexes through host-guest interactions. On the other hand, T85 is an amphiphilic molecule and, consequently, has the potential to increase hydrophilic drug loading within the hydrogels. In the present work, a new type of hydrogel made from poly(methyl vinyl ether-co-maleic acid) (GAN) and poly(ethylene glycol) (PEG) containing T85 and HPBCD was synthesized for hydrophobic drug release. Hydrogels were based on GAN crosslinked (PEG) and HPBCD and/or T85 via an esterification in the solid state (solvent free). The synthesised hydrogels were characterised using Fourier transform infrared (FTIR) spectroscopy, swelling studies and contact angle measurements. The hydrogels showed swellings ranging from 140 to 180%. The inclusion of T85 in the hydrogels improved the wettability of the materials. On the other hand, the inclusion of HPBCD within the hydrogels decreased the wettability as the contact angle between the hydrogels and water increased with the HPBCD content. Finally, the materials were loaded with an ophthalmic drug, dexamethasone (DX). HPBC-containing hydrogels showed a higher DX uptake and, consequently, also a higher capacity of DX release. On the other hand, T85 containing hydrogels did not show any improvement over the hydrogels containing only GAN and PEG. The hydrogels were able to provide sustained DX release over periods of 6 h.
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