Design and Engineering of Biodegradable 3D Nanoprinted Microcarriers for HIV Drug Delivery

精确、可定制的药物输送仍然是一个长期目标，尤其是对艾滋病毒而言 技术将允许根据患者的生物构成量身定做治疗方法，并有可能 提高遵从性。延长释放的方法解决了部分问题，但面临局限性。一个 新的药物传递系统可以通过口服和新的途径提供更好的儿科给药 行政管理。现有的缓释方法有限：液体药物的行业标准 微载流子制造受到制造引起的限制，包括：(I)限制 微载体几何结构；(2)不希望的载体之间的可变性；(3)难以 多药微载体生产；和(Iv)极其不切实际的按需途径 微载体结构和组合物的改进。快速多材料三- 充满液体的微容器的三维(3D)纳米打印提供了革命性的潜力 通过以下途径解决上述痛点，生产治疗性微载体： 无与伦比的3D多功能性微载体设计，(Ii)100纳米尺度的特征分辨率，(Iii)快速， 多材料生产，以及(Iv)按需定制每个单独的微载体。 概念验证已经通过打印人体大小的3D微容器进行了演示 含有标准(即，非生物)光致抗蚀剂的上皮细胞 流体。目前的重点是设计基于生物相容性和可生物降解性的微载体 具有微载体结构的材料，包括：(1)可生物降解的外壳，具有 顶部的孔口，(2)(至少一个)治疗性液体“有效载荷”的核心，以及(3)定制设计的 贝壳上的可生物降解的“帽子”。在规模上，这一战略可能会产生延长发布时间 微载体，每个盖子设计(因此，生物降解动力学)提供独特的， 靶向释放动力学。更好的稳定性和不积聚是额外的优势。 建议的具有基于设计的释放特性的多材料微载体架起了 重要需求，特别是对艾滋病毒的需求。量身定制的充液微载体的创新 这种规模的建筑和成分提供了精确的剂量和治疗选择- 例如，联合疗法和释放率控制--否则是无法实现的。这项工作将 研究设计和工程3D多材料微载体的建议策略 用于超缓释治疗用途。

Precise, customizable drug delivery remains a long-term goal, for HIV in particular, as such technologies would allow therapies tailored to a patient’s biological makeup and potentially improve adherence. Extended-release methods address part of the issue, but face limitations. A novel drug delivery system could offer better pediatric dosing, via both oral and new routes of administration. Existing extended-release methods are limited: industry standards for liquid-drug microcarrier fabrication are restricted by manufacturing-induced constraints, including: (i) limited micro-carrier geometries; (ii) undesired carrier-to-carrier variability; (iii) difficult means of multidrug microcarrier production; and (iv) exceedingly impractical pathways to on-demand modifications of microcarrier architectures and compositions. Rapid multi-material three- dimensional (3D) nanoprinting of liquid-filled microcontainers offers the potential to revolutionize the production of therapeutic microcarriers by addressing the aforementioned pain points via: (i) unparalleled 3D versatility in microcarrier design, (ii) 100-nm-scale feature resolution, (iii) rapid, multi-material production, and (iv) on-demand customization of each individual microcarrier. Proof of concept has been demonstrated by printing 3D microcontainers the size of human epithelial cells comprising standard (i.e., non-biological) photoresists encompassing an aqueous fluid. The current focus is to engineer microcarriers based on biocompatible and biodegradable materials, with microcarrier architectures composed of: (1) a biodegradable outer “shell” with an orifice on top, (2) a core of (at least one) therapeutic liquid “payload”, and (3) a custom-designed biodegradable “cap” atop the shell. At scale, this strategy could produce extended-release microcarriers, with each cap design (and thus, biodegradation dynamics) offering distinct, targeted release kinetics. Improved stability and non-accumulation are additional advantages. The proposed multi-material microcarriers with design-based release properties bridge an important need, especially for HIV. The innovation of liquid-filled microcarriers with tailor-made architectures and compositions at this scale offers precision dosing and therapeutic options— e.g., combination therapies and release rate controls—not otherwise achievable. The work will investigate the proposed strategy for designing and engineering 3D multi-material microcarriers for ultra-extended-release therapeutic uses.