Nanobiomaterials Lab, CINDEFI, School of Sciences, National University of La Plata-CONICET (CCT La Plata), 50 & 115 street, CP 1900 AJL, City of La Plata, Buenos Aires, Argentina.
Chemical Inorganic Center (CEQUINOR, UNLP, CONICET), School of Sciences, National University of La Plata-CONICET (CCT La Plata), CP 1900 AJL, City of La Plata, Buenos Aires, Argentina.
Colloids Surf B Biointerfaces. 2018 Oct 1;170:596-608. doi: 10.1016/j.colsurfb.2018.06.056. Epub 2018 Jun 26.
The use of hybrid materials, where a matrix sustains nanoparticles controlling the release of the chemotherapeutic drug, could be beneficial for the treatment of primary tumors prior or after surgery. This localized chemotherapy would guarantee high drug concentrations at the tumor site while precluding systemic drug exposure minimizing undesirable side effects. We combined bacterial cellulose hydrogel (BC) and nanostructured lipid carriers (NLCs) including doxorubicin (Dox) as a drug model. NLCs loaded with cationic Dox (NLCs-H) or neutral Dox (NLCs-N) were fully characterized and their cell internalization and cytotoxic efficacy were evaluated in vitro against MDA-MB-231 cells. Thereafter, a fixed combination of NLCs-H and NLCs-N loaded into BC (BC-NLCs-NH) was assayed in vivo into an orthotopic breast cancer mouse model. NLCs-H showed low encapsulation efficiency (48%) and fast release of the drug while NLCs-N showed higher encapsulation (97%) and sustained drug release. Both NLCs internalized via endocytic pathway, while allowing a sustained release of the Dox, which in turn rendered IC50 values below of those of free Dox. Taking advantage of the differential drug release, a mixture of NLCs-N and NLCs-H was encapsulated into BC matrix (BC-NLCs-NH) and assayed in vivo, showing a significant reduction of tumor growth, metastasis incidence and local drug toxicities.
使用混合材料，其中基质维持控制化疗药物释放的纳米颗粒，可以有利于原发性肿瘤的治疗，无论是在手术前还是手术后。这种局部化疗将保证肿瘤部位的高药物浓度，同时排除全身药物暴露，最大限度地减少不良副作用。我们将细菌纤维素水凝胶 (BC) 和包含阿霉素 (Dox) 的纳米结构化脂质载体 (NLC) 结合在一起作为药物模型。负载阳离子 Dox 的 NLC (NLCs-H) 或中性 Dox 的 NLC (NLCs-N) 被充分表征，并在体外对 MDA-MB-231 细胞进行细胞内化和细胞毒性评估。此后，将负载 NLCs-H 和 NLCs-N 的固定混合物装入 BC（BC-NLCs-NH），并在原位乳腺癌小鼠模型中进行体内检测。NLCs-H 显示出低的包封效率（48%）和快速释放药物，而 NLCs-N 显示出更高的包封效率（97%）和持续的药物释放。两种 NLCs 都通过内吞途径内化，同时允许 Dox 的持续释放，从而使 IC50 值低于游离 Dox 的 IC50 值。利用药物释放的差异，将 NLCs-N 和 NLCs-H 的混合物包封在 BC 基质中（BC-NLCs-NH）并在体内进行检测，显示出肿瘤生长、转移发生率和局部药物毒性的显著降低。
