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，特别是对于艾滋病毒而言 技术将允许根据患者的生物构成定制治疗， 改善粘附性。延长释放的方法解决了部分问题，但面临限制。一 新的药物输送系统可以提供更好的儿科剂量，通过口服和新的途径， 局现有的延长释放方法是有限的：液体药物的行业标准 微载体制造受到制造引起的约束的限制，包括：（i）有限的 微载体几何形状;（ii）不期望的载体与载体之间的可变性;（iii） 多药物微载体生产;和（iv）按需生产的极其不切实际的途径 微载体结构和组合物的修饰。快速多物料三- 三维（3D）纳米打印的液体填充微容器提供了革命性的潜力 治疗性微载体的生产通过以下方式解决上述痛点：（i） 微载体设计中无与伦比的3D多功能性，（ii）100 nm尺度的特征分辨率，（iii）快速， 多材料生产，和（iv）按需定制每个单独的微载体。 通过打印人体大小的3D微容器证明了概念的证明 上皮细胞包括标准的（即，非生物）光致抗蚀剂， 液目前的重点是基于生物相容性和生物可降解性设计微载体 材料，具有微载体结构，该微载体结构由以下组成：（1）可生物降解的外部“壳”， （2）（至少一种）治疗液体“有效载荷”的芯，和（3）定制设计的 可生物降解的“帽子”上的外壳。在大规模，这种策略可以产生延长释放 微载体，每个帽设计（因此，生物降解动力学）提供不同的， 靶向释放动力学。提高稳定性和不积累是额外的优点。 所提出的具有基于设计的释放特性的多材料微载体桥接了 重要需求，特别是艾滋病毒。定制化液体填充微载体的创新 这种规模的结构和组合物提供了精确的剂量和治疗选择- 例如，在一个实施例中，联合治疗和释放速率控制-否则无法实现。这项工作将 研究设计和工程化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.