Shear induced carboplatin binding within the cavity of a phospholipid mimic for increased anticancer efficacy

Abstract

Vesicles 107 ± 19 nm in diameter, based on the self-assembly of tetra-para-phosphonomethyl calix[4]- arene bearing n-hexyl moieties attached to the phenolic oxygen centres, are effective in binding carboplatin within the cavity of the macrocycle under shear induced within a dynamic thin film in a continuous flow vortex fluidic device. Post shearing the vesicles maintain similar diameters and retain carboplatin within the cavity of the calixarene in a hierarchical structure, with their size and morphology investigated using DLS, TEM, SEM and AFM. Location of the carboplatin was confirmed using NMR, FTIR, ESI-MS and EFTEM, with molecular modelling favouring the polar groups of carboplatin hydrogen bonded to phosphonic acid moieties and the four member cyclobutane ring directed into the cavity of the calixarene. The loading efficiency and release profile of carboplatin was investigated using LC-TOF/MS, with the high loading of the drug achieved under shear and preferential released at pH 5.5, offering scope for anti-cancer drug delivery. The hierarchical structured vesicles increase the efficacy of carboplatin by 4.5 fold on ovarian cancer cells, lowered the IC50 concentration by 10 fold, and markedly increased the percent of cells in the S-phase (DNA replication) of the cell cycle.

Multifunctional nanoparticles for co-delivery of paclitaxel and carboplatin against ovarian cancer by inactivating the JMJD3-HER2 axis

“…6 As shown in Fig. 2C, Fp-PCN PAC+CAR was stable at pH 7.4, releasing only 20% of its PAC and CAR cargoes after 2 days at 37°C.…”

“…6,7 The encapsulation efficiency (EE) of PAC was 89.67 ± 6.57% and that of CAR was 55.4 ± 3.47% in PCN carriers. When placed into Fp-PCN carriers according to a previous method with a minor modification, 6 the EE of PAC (88.45 ± 5.19%) and CAR (48.6 ± 5.47%) were changed a little (Table 2). We found that the molar ratio of PAC to CAR in both PCN and Fp-PCNs is fixed (about 1 : 0.2) regardless of the feeding concentration of the drugs.…”

Curcumin: a calixarene derivative micelle potentiates anti-breast cancer stem cells effects in xenografted, triple-negative breast cancer mouse models

“…POCA4C6 was synthesized as described (Mo et al, 2015), in which the lowest-yield step of formulation (70% yield) was adapted from Dondoni et al (1997). Briefly, n-hexyl groups were added to calix [4]arene in DMF using bromohexane and sodium hydride, formulation was carried out via the Duff reactio, and the formulated product was reduced to the corresponding alcohol using sodium borohydride.…”

“…POCA4C6 has been shown to self-assemble into vesicles or micelles that can encapsulate drugs and release them in a pH-dependent manner (Mo et al, 2015(Mo et al, , 2016. In addition to serving as a drug delivery platform, calixarene itself can show therapeutic activity: calixarene derivatives can inhibit cancer cell proliferation and invasion as well as tumor angiogenesis by inhibiting signaling pathways (Astorgues-Xerri et al, 2014).…”

Fabrication of Nanofiber Filtration Membranes Using Polyethylene Terephthalate (PET): A Review

“…So related to wanted condition, one of these two modes would be selected. Some other narrative researches that have been performed with the help of VFD are involved bacteria and algal cells with graphene and magnetic polymer [78][79][80], protein folding [81], exfoliating single layered graphene and hexagonal Boron Nitride (h-BN) sheets from the bulk material [82], sol-gel synthesis of silica xero gel at room temperature and the incorporation of curcumin, [83] controlling the pore size and wall thickness of mesoporous silica [84,85], fabricating toroidal arrays of SWCNTs, [86] laterally 'slicing' CNTs, [87] accelerating enzymatic reaction, [88] probing the structure of self-organized systems [89,90], biodiesel catalysis [91] and many others. According to the extra capabilities of VFD as a various reaction media compared with Spinning Disc Processors (SDPs) or Rotating Tube Processors (RTPs), VFD will be more advantageous in reaction accomplishment [92].…”