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Delivery of Immune Checkpoint Inhibitors Using Nanoparticles
Published in Hala Gali-Muhtasib, Racha Chouaib, Nanoparticle Drug Delivery Systems for Cancer Treatment, 2020
Abdullah Shaito, Houssein Hajj Hassan
Methoxy poly(-ethylene glycol)3000poly(ε-caprolactone)20000 [MPEG-PCL] and maleimide-poly (ethylene glycol)3400-poly(ε-caprolactone)20000 [Mal-PEG-PCL] nanoparticles were conjugated to the CD peptide to form CD NPs, CD-NP. The CD peptide is a PD-1 targeting peptide that consisted of DPPA-1 peptide, a peptide derived from PDL-1, and the peptide CGKRK, a tumor vasculature affinity peptide. The CD-NPs were further conjugated to the paclitaxel (PTX) chemotherapeutic agent to form CD-NP-PTX nanoparticles. The combination therapy nanoparticles, CD-NP-PTX, could improve the tumor targeting, delivery, efficacy, and antitumor effects of checkpoint inhibitors against glioma cells in vivo [122].
Long-term stability of insulin glulisine loaded nanoparticles formulated using an amphiphilic cyclodextrin and designed for intestinal delivery
Published in Drug Development and Industrial Pharmacy, 2020
Elena Presas, Eric Sultan, Valeria Gervasi, Abina M. Crean, Ulrich Werner, Didier Bazile, Caitriona M. O’Driscoll
Previously, we have shown that a dispersion of the CD-based insulin glulisine NPs (50 IU/kg) as described here produced a progressive and significant reduction of blood glucose levels following in situ instillation in healthy anesthetized rats (≈50% after 45 min maintained up to 4 h [9]). However, these NPs exhibited a poor stability profile following long-term storage as a colloidal dispersion. Although the freeze-dried product successfully extended the long-term colloidal stability of the NPs, the biological response anticipated was not achieved. Possible reasons for the lack of biological activity include the influence of the freeze drying process on the structural integrity of the peptide. The incorporation of the trehalose may also have an impact. Although little is known about the effect of cryoprotectants on NPs, some evidence exists to suggest a possible alteration in porosity of the nanostructures, which may have an impact on protein release in a biological environment [22]. In addition, the lack of response may be related to the animal model used. In the previous study [9], the formulation was instilled into an isolated intestinal loop thus prolonging contact with the absorption membrane. In contrast, in this study, the dose was administered as a single bolus into the intestine, exposing the formulation to dilution by the intestinal fluid. In summary, while the production of a freeze-dried CD NP was achieved, further formulation and processing optimization is required to achieve a therapeutically relevant response.
PD-1/PD-L1 pathway and angiogenesis dual recognizable nanoparticles for enhancing chemotherapy of malignant cancer
Published in Drug Delivery, 2018
Zhenliang Sun, Yang Zhang, Duo Cao, Xufeng Wang, Xuebing Yan, Hao Li, Linsheng Huang, Xiao Qu, Cheng Kong, Huanglong Qin, Man Wang, Wei Xu, Lin Liang
The effect of PTX formulations on the formation of angiogenesis was evaluated in this study. As shown in Figure 4(B,C), the drug-free DMEM treated group exhibited the most extensive and enclosed tube networks compared with others. After exposed to Taxol®, a negligible tube formation inhibition was observed. However, a less channel destruction could be obtained by incubating cells with NP-PTX. After decoration of nanoparticles with CGKRK peptides, the angiogenesis was significantly inhibited, indicating a highly angiogenesis homing property of this peptide. In contrast, there was no obvious difference between the group treated by NP-PTX and D-NP-PTX, which was mainly because the fact of DPPA-1 is just a tumor cell recognizable peptide. In this case, the C-NP-PTX and CD-NP-PTX treated group displayed the similar activity in anti-angiogenesis formation.