Thermosensitive biomaterial gels with chemical permeation enhancers for enhanced microneedle delivery of naltrexone for managing opioid and alcohol dependency.
Thermosensitive biomaterial gels with chemical permeation enhancers for enhanced microneedle delivery of naltrexone for managing opioid and alcohol dependency.
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DOI：
10.1039/d3bm00972f
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发表时间：
2023-08-22
影响因子：
6.6
通讯作者：
中科院分区：
文献类型：
--
作者：
纳洛酮（NTX）可以使用微针（MN）经皮递送以治疗阿片类药物和酒精滥用障碍，但是递送被体内快速的血管闭合所钝化。泊洛沙姆（P407）是一种热敏性生物相容性水凝胶，通过在微孔内产生药物贮库来维持NTX通过MN处理的皮肤的递送。优化P407制剂可以在子宫内膜闭合后保持持续递送，同时减少所需的贴剂尺寸，这将更谨慎，并受到大多数患者的青睐。在这里，我们开发了具有化学渗透促进剂（CPE）的NTX负载的P407凝胶，并使用这些新的制剂与MN治疗一起使用，以利用平行的皮肤和完整的皮肤转运途径来增强NTX渗透。我们分析了CPE负载的P407制剂的物理化学和流变学性质，并选择了DMSO和苯甲醇的制剂用于进一步研究。体外渗透试验表明，与水溶液相比，16%P407制剂通过MN处理的猪皮的NTX递送更一致和持续。P407与1%苯甲醇和10%DMS0相比，显著地（P < 0.05）增加了通过MN处理的皮肤的通量。这种制剂需要比以前用于在人体中递送NTX的更小尺寸的贴剂，具有NTX浓度的一半。这是泊洛沙姆生物材料首次与CPE联合使用，以改善阿片类拮抗剂的MN辅助透皮给药。在这里，我们已经证明，P407与CPE组合有效地维持了MN处理的皮肤中的NTX递送，同时需要比以前更少的NTX来满足临床目标。纳洛酮（NTX）可以使用微针（MN）经皮递送以治疗阿片类药物和酒精滥用障碍，但是递送被体内快速的血管闭合所钝化。
Naltrexone (NTX) can be transdermally delivered using microneedles (MN) to treat opioid and alcohol misuse disorders, but delivery is blunted by rapid in vivo micropore closure. Poloxamer (P407), a thermosensitive biocompatible hydrogel, sustains NTX delivery through MN-treated skin by generating a drug depot within the micropores. Optimizing P407 formulations could maintain sustained delivery after micropore closure while reducing required patch sizes, which would be more discreet and preferred by most patients. Here we developed NTX-loaded P407 gels with chemical permeation enhancers (CPEs) and used these novel formulations alongside MN treatment to enhance NTX permeation, utilizing parallel micropore and intact skin transport pathways. We analyzed physicochemical and rheological properties of CPE-loaded P407 formulations and selected formulations with DMSO and benzyl alcohol for further study. In vitro permeation tests demonstrated more consistent and sustained NTX delivery through MN-treated porcine skin from 16% P407 formulations vs. aqueous solutions. P407 with 1% benzyl alcohol and 10% DMSO significantly, P < 0.05, increased flux through MN-treated skin vs. formulations with benzyl alcohol alone. This formulation would require a smaller size patch than previously used to deliver NTX in humans, with half the NTX concentration. This is the first time poloxamer biomaterials have been used in combination with CPEs to improve MN-assisted transdermal delivery of an opioid antagonist. Here we have demonstrated that P407 in combination with CPEs effectively sustains NTX delivery in MN-treated skin while requiring less NTX than previously needed to meet clinical goals. Naltrexone (NTX) can be transdermally delivered using microneedles (MN) to treat opioid and alcohol misuse disorders, but delivery is blunted by rapid in vivo micropore closure.
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影响因子：
3.7
作者：
Kalluri, Haripriya;Banga, Ajay K.
通讯作者：
Banga, Ajay K.
DOI：
10.1016/j.jpba.2006.05.018
发表时间：
2006-11-16
影响因子：
3.4
作者：
Cardoso, Valeria Macedo;Reis Solano, Ana Gabriela;Nunan, Elziria de Aguiar
通讯作者：
Nunan, Elziria de Aguiar
影响因子：
4.9
作者：
Ghosh P;Brogden NK;Stinchcomb AL
通讯作者：
Stinchcomb AL
影响因子：
4.8
作者：
Bodratti AM;Alexandridis P
通讯作者：
Alexandridis P
影响因子：
3.7
作者：
Banks SL;Paudel KS;Brogden NK;Loftin CD;Stinchcomb AL
通讯作者：
Stinchcomb AL