School of Pharmacy, Queen's University Belfast, 97 Lisbrurn Road, Belfast BT9 7BL, UK; Department of Biomolecular Sciences, University of Urbino Carlo Bo, Piazza del Rinascimento, 6, 61029 Urbino (PU), Italy.
School of Pharmacy, Queen's University Belfast, 97 Lisbrurn Road, Belfast BT9 7BL, UK.
Int J Pharm. 2023 Jul 25;642:123154. doi: 10.1016/j.ijpharm.2023.123154. Epub 2023 Jun 17.
Breast-conserving surgery (BCS) is the primary strategy for treating early-stage breast cancer; however, the incidence of local recurrence and breast tissue loss negatively impacts patients and survivors. Furthermore, radiotherapy and/or systemic therapies are frequently advised to avoid recidivism and increase the patient's chance of survival, resulting in longer duration of treatments, and unpleasant systemic side effects. Given the poor prognosis and the heterogeneity between individuals and tumors, a patient-centered approach is fundamental. Herein we developed a multipurpose 4D printed implant made of a blend of carboxymethyl cellulose sodium salt (CMC) and cellulose nanocrystals (CNC), loaded with doxorubicin (DOX). To predict printability performance, full rheological characterization was carried out. The smart device was programmed to change size, under swelling, to better fit in the tissue cavity, resulting in a great potential for personalization, thus improving the aesthetic outcomes. The influence of the formulation and printing parameters on the morpho transformation was investigated through the swelling test, confirming the possibility to program the 4D shape. The manufactured implants were characterized by a variety of methods, including in vitro release studies. Lastly, the anticancer activity was conducted in vitro, on MDA-MB-231 cells. Implants promoted an anticancer effect of -58% viability after 72 h incubation, even when tested 4 weeks after the printing process. Overall, the morpho transformation and the in vitro studies have shown that the implant could represent a potential strategy for breast cancer following resection, to fill the void in the breast resulting from the surgery and provide an anticancer effect to avoid recurrence.
保乳手术（BCS）是治疗早期乳腺癌的主要策略；然而，局部复发和乳房组织丢失的发生率对患者和幸存者产生负面影响。此外，通常建议进行放疗和/或系统治疗，以避免复发并增加患者的生存机会，从而延长治疗时间，并产生不愉快的全身副作用。鉴于预后不良以及个体和肿瘤之间的异质性，以患者为中心的方法至关重要。在此，我们开发了一种由羧甲基纤维素钠（CMC）和纤维素纳米晶体（CNC）混合物制成的多用途 4D 打印植入物，负载多柔比星（DOX）。为了预测可打印性能，进行了全面的流变学特性分析。该智能装置经过编程可在肿胀时改变尺寸，以更好地适应组织腔，从而具有很大的个性化潜力，从而改善美容效果。通过溶胀试验研究了配方和打印参数对形态转变的影响，证实了对 4D 形状进行编程的可能性。通过各种方法对制造的植入物进行了表征，包括体外释放研究。最后，在体外对 MDA-MB-231 细胞进行了抗癌活性测试。植入物在孵育 72 小时后可将细胞活力降低 58%，即使在打印过程 4 周后进行测试也是如此。总体而言，形态转变和体外研究表明，该植入物可能是乳腺癌切除术后的一种潜在策略，可用于填充手术引起的乳房空洞，并提供抗癌作用以避免复发。
