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Solid Lipid Nanoparticles for Anti-Tumor Drug Delivery
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
Ho Lun Wong, Yongqiang Li, Reina Bendayan, Mike Andrew Rauth, Xiao Yu Wu
Paclitaxel (Taxol) is an anti-microtubule agent with broad spectrum anti-tumor activities. It is gaining popularity among oncologists for its effectiveness against several types of malignancies, even when used alone.95 Paclitaxel is a poorly water-soluble drug. At present, it is commercially available as a non-aqueous micellar solution containing a polyoxyethylated castor oil Cremophor EL and 49.7% dehydrated ethanol. Cremophor EL is known to cause serious hypersensitivity reactions and nephrotoxicity in human subjects.96 In order to solubilize paclitaxel without the need for Cremophor EL, a few SLN formulations have been developed and studied.62,82–86 In general, the drug loading in these SLN formulations ranged from 2 to 5%. In these SLN formulations, surfactants or stabilizers such as Pluronic® F68 (i.e., poloxamer 188), Brij-78, and phosphatidylcholine were used. In comparison to Cremophor EL, all of these excipients are commonly included in parenteral formulations with better track records of safety.
A retrospective analysis of cisplatin/carboplatin plus paclitaxel in advanced or recurrent cervical cancer
Published in Journal of Obstetrics and Gynaecology, 2019
Dan Song, Weimin Kong, Tongqing Zhang, Chao Han, Tingting Liu, Simeng Jiao, Jiao Chen
Cisplatin is a cell cycle-non-specific agent that interacts with DNA base-pairs to inhibit replication (Xu et al. 2015). Paclitaxel is an anti-microtubule agent that prevents the formation of spindle and spindle silk during mitosis and affects the G2 and M phases by specifically inhibiting the tumour cellular cleavage and proliferation (Slama et al. 2012). The combination of cisplatin and paclitaxel has been widely used as a palliative therapy in the treatment of stage IVB or recurrent cervical cancer with superior efficacy (Monk et al. 2009). Unfortunately, cisplatin has been associated with severe toxicities, particularly gastrointestinal and renal toxicities, which often inspire great fear and result in poor compliance in patients. Moreover, the adverse effects and requirement of hydration treatment associated with the TP regimen may prolong hospitalisation despite its favourable clinical outcomes. In light of these disadvantages, new alternatives are needed to reduce adverse reactions without decreasing therapeutic effectiveness.
Efficacy of nab-paclitaxel in treating metastatic melanoma
Published in Expert Opinion on Pharmacotherapy, 2019
nab-Paclitaxel is a solvent-free human serum albumin-paclitaxel nanoparticle of approximately 130 nm in size, where the paclitaxel is present in a non-crystalline, amorphous state. Paclitaxel is an antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or ‘bundles’ of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis [7]. Upon intravenous administration of nab-paclitaxel, the nanoparticles dissociate rapidly into soluble, albumin bound paclitaxel complexes of approximately 10 nm in size. Albumin is known to mediate endothelial caveolar transcytosis of plasma constituents, and in vitro studies demonstrated that the presence of albumin in nab-paclitaxel enhances transport of paclitaxel across endothelial cells. It is hypothesized that this enhanced transendothelial caveolar transport is mediated by the gp-60 albumin receptor, and that there is enhanced accumulation of paclitaxel in the area of tumor due to the albumin-binding protein Secreted Protein Acidic Rich in Cysteine (SPARC) [7].
New drugs in early development for treating multiple myeloma: all that glitters is not gold
Published in Expert Opinion on Investigational Drugs, 2020
Luca Bertamini, Francesca Bonello, Mario Boccadoro, Sara Bringhen
Belantamab mafodotin is the first anti-BCMA ADC conjugated with the toxic anti-microtubule agent MMAF. In addition to its activity due to MMAF, belantamab mafodotin also induces immunogenic cell death by ADCP and ADCC [100,113]. The first in-human single-agent activity was studied in the phase I/II DREAMM-1 trial. Overall, 73 patients were enrolled, the majority of whom were heavily pretreated. Main toxicities were ophthalmologic and hematologic (any-grade thrombocytopenia 61%). Ocular toxicity consisted mainly of blurred vision (52%) and keratitis (9%) and was likely related to MMAF, also considering that similar AEs were reported with other ADCs with MMAF [114]. G3-4 AEs were mostly hematologic and IRRs occurred only in 6% of patients. The efficacy report was encouraging, with an ORR of 60%, including 5 patients achieving at least a CR and 14 a VGPR, and a median PFS of 12 months [115,116]. The phase II DREAMM-2 study evaluated 2 drug doses (2.5 mg/kg and 3.4 mg/kg) in patients relapsed or refractory to PIs, IMDs and anti-CD38. A specific attention was put on the management of ocular toxicity, the prevention through periodic ocular examination by ophthalmologists and the administration of steroid eye drops, artificial tears and cooling eye masks. The most frequent ocular-referred symptoms were blurred vision and dry eye. In the two cohorts, 36% and 28% of patients with ocular AEs recovered. A longer follow-up is needed to understand the long-term evolution of ocular toxicity. G≥3 AEs were keratopathy (27% and 21% in the 2.5 mg/kg and 3.4 mg/kg cohorts, respectively), thrombocytopenia (20% and 33%), and anemia (20% and 25%). Dose reductions were frequent (29% and 41%) and mainly due to ocular toxicity. IRRs occurred in 15% and 18% of patients and were mostly G1-2 and limited to the first infusion.