Amphiphilic brush polymers produced using the RAFT polymerisation method stabilise and reduce the cell cytotoxicity of lipid lyotropic liquid crystalline nanoparticles

2016 ◽  
Vol 191 ◽  
pp. 545-563 ◽  
Author(s):  
Jiali Zhai ◽  
Randy Suryadinata ◽  
Bao Luan ◽  
Nhiem Tran ◽  
Tracey M. Hinton ◽  
...  
Keyword(s):  
Liquid Crystalline ◽  
Water Channel ◽  
Pluronic F127 ◽  
Cubic Phase ◽  
Valuable Insight ◽  
Liquid Crystalline Nanoparticles ◽  
Self Assembled ◽  
Poly Ethylene ◽  
Double Diamond

Self-assembled lipid lyotropic liquid crystalline nanoparticles such as hexosomes and cubosomes contain internal anisotropic and isotropic nanostructures, respectively. Despite the remarkable potential of such nanoparticles in various biomedical applications, the stabilisers used in formulating the nanoparticles are often limited to commercially available polymers such as the Pluronic block copolymers. This study explored the potential of using Reversible Addition-Fragmentation chain Transfer (RAFT) technology to design amphiphilic brush-type polymers for the purpose of stabilising phytantriol and monoolein-based lipid dispersions. The synthesised brush-type polymers consisted of a hydrophobic C12 short chain and a hydrophilic poly(ethylene glycol)methyl ether acrylate (PEGA) long chain with multiple 9-unit poly(ethylene oxide) (PEO) brushes with various molecular weights. It was observed that increasing the PEO brush density and thus the length of the hydrophilic component improved the stabilisation effectiveness for phytantriol and monoolein-based cubosomes. Synchrotron small-angle X-ray scattering (SAXS) experiments confirmed that the RAFT polymer-stabilised cubosomes had an internal double-diamond cubic phase with tunable water channel sizes. These properties were dependent on the molecular weight of the polymers, which were considered in some cases to be anisotropically distributed within the cubosomes. The in vitro toxicity of the cubosomes was assessed by cell viability of two human adenocarcinoma cell lines and haemolytic activities to mouse erythrocytes. The results showed that phytantriol cubosomes stabilised by the RAFT polymers were less toxic compared to their Pluronic F127-stabilised analogues. This study provides valuable insight into designing non-linear amphiphilic polymers for the effective stabilisation and cellular toxicity improvement of self-assembled lipid lyotropic liquid crystalline nanoparticles.

Rutin loaded liquid crystalline nanoparticles inhibit non-small cell lung cancer proliferation and migration in vitro

Life Sciences ◽  
2021 ◽  
Vol 276 ◽  
pp. 119436
Author(s):  
Keshav Raj Paudel ◽  
Ridhima Wadhwa ◽  
Xin Nee Tew ◽  
Natalie Jia Xin Lau ◽  
Thiagarajan Madheswaran ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Liquid Crystalline ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cancer Proliferation ◽  
Liquid Crystalline Nanoparticles ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals Liquid crystalline systems containing Vitamin E TPGS for the controlled transdermal nicotine delivery

2016 ◽  
Vol 52 (1) ◽  
pp. 191-200 ◽  
Author(s):  
Lívia Neves Borgheti-Cardoso ◽  
Fabiana Testa Moura de Carvalho Vicentini ◽  
Tais Gratieri ◽  
Maria Vitória Lopes Badra Bentley
Keyword(s):  
Vitamin E ◽  
Liquid Crystalline ◽  
Visual Analysis ◽  
Skin Permeation ◽  
Skin Irritation ◽  
Cubic Phase ◽  
Nicotine Delivery ◽  
Vitamin E Tpgs ◽  
Transdermal Nicotine

ABSTRACT Transdermal nicotine patches have been used in smoking cessation therapy, suggested for the treatment of skin disorders with eosinophilic infiltration and have been found to improve attention performance in patients with Alzheimer's disease and age-associated memory impairment. However, skin irritation with extended patch use is still a problem. The aim of this work was to develop a simple to prepare liquid crystalline system containing vitamin E TPGS that would be able to control nicotine delivery and reduce irritation and sensitization problems. The liquid crystalline phases were macroscopically characterized by visual analysis and examined microscopically under a polarized light microscope. Topical and transdermal delivery of nicotine were investigated in vitro using porcine ear skin mounted on a Franz diffusion cell. Nicotine skin permeation from the developed cubic phase followed zero-order kinetics (r = 0.993) and was significantly enhanced after 12 h when compared to the control formulation (nicotine solution) (p < 0.05) (138.86 ± 20.44 and 64.91 ± 4.06 μg/cm2, respectively). Cubic phase was also able to target viable skin layers in comparison to control solution (8.18 ± 1.89 and 2.63 ± 2.51 μg/cm2, respectively). Further studies to evaluate skin sensitization and irritation are now necessary.

Using Mass Spectrometry to Investigate the Structural Features of Photocrosslinked Co-Networks based on Gelatin and Poly(ethylene glycol) Methacrylates

2012 ◽  
Vol 1403 ◽  
Author(s):  
Benjamin F. Pierce ◽  
Axel T. Neffe ◽  
Andreas Lendlein
Keyword(s):  
Mass Spectrometry ◽  
Ethylene Glycol ◽  
Degradation Products ◽  
Structural Features ◽  
Valuable Insight ◽  
Poly Ethylene Glycol ◽  
Buffer Solution ◽  
Molecular Weight Range ◽  
Poly Ethylene

ABSTRACTGelatin was functionalized with glycidyl methacrylate and photocrosslinked in the presence of poly(ethylene glycol) dimethacrylate (PEGDMA) or poly(ethylene glycol) monomethacrylate (PEGMA) to create a biopolymer-based system with tailorable properties. These co-networks were hydrolyzed using 6 M HCl and the degradation products were analyzed and identified using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. This technique successfully identified gelatin-derived peptides such as FLPEPPE, SFLPEPPE, and SFLPEPPEE as well as an accompanying PEG-g-poly(methacrylic acid) component. No oligo- or polymethacrylates were monitored at any molecular weight range above m/z = 500, which indicated that they possessed lower molecular weights. An in vitro hydrolytic degradation experiment performed in pH 7.4 PBS buffer solution at 37 °C showed that these networks, which were prepared without the addition of a potentially toxic photoinitiator, exhibited mass loss of up to 50 wt% at 6 weeks of incubation time. These results provide valuable insight into how these functional gelatin-based co-network biomaterials will perform in a biological setting.

scholarly journals Ophthalmic Delivery of Brinzolamide by Liquid Crystalline Nanoparticles: In Vitro and In Vivo Evaluation

2013 ◽  
Vol 14 (3) ◽  
pp. 1063-1071 ◽  
Author(s):  
Weijun Wu ◽  
Jing Li ◽  
Lin Wu ◽  
Baoyan Wang ◽  
Zhongyuan Wang ◽  
...  
Keyword(s):  
Liquid Crystalline ◽  
In Vivo Evaluation ◽  
Ophthalmic Delivery ◽  
Liquid Crystalline Nanoparticles

scholarly journals Development of Self-Associating SN-38-Conjugated Poly(ethylene oxide)-Poly(ester) Micelles for Colorectal Cancer Therapy

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1033
Author(s):  
Sams M. A. Sadat ◽  
Mohammad Reza Vakili ◽  
Igor M. Paiva ◽  
Michael Weinfeld ◽  
Afsaneh Lavasanifar
Keyword(s):  
Colorectal Cancer ◽  
Ethylene Oxide ◽  
Water Solubility ◽  
In Vitro Release ◽  
Critical Micellar Concentration ◽  
Anticancer Activities ◽  
Poly Ethylene Oxide ◽  
Self Assembled ◽  
Poly Ethylene

The clinical use of 7-ethyl-10-hydroxy-camptothecin (SN-38), which is the active metabolite of irinotecan, has been hampered because of its practical water-insolubility. In this study, we successfully synthesized two self-associating SN-38-polymer drug conjugates to improve the water-solubility of SN-38, while retaining its anticancer activity. The polymeric micellar SN-38 conjugates were composed of either methoxy-poly(ethylene oxide)-block-poly(α-benzyl carboxylate-ε-caprolactone) conjugated to SN-38 at the PBCL end (mPEO-b-PBCL/SN-38) or mPEO-block-poly(α-carboxyl-ε-caprolactone) attached to SN-38 from the pendent-free carboxyl site (mPEO-b-PCCL/SN-38). The chemical structure of block copolymers was confirmed by 1H NMR. The physicochemical characterizations of their self-assembled structures including size, surface charge, polydispersity, critical micellar concentration, conjugation content and efficiency, morphology, kinetic stability, and in vitro release of SN-38 were compared between the two formulations. In vitro anticancer activities were evaluated by measuring cellular cytotoxicity and caspase activation by MTS and Caspase-Glo 3/7 assays, respectively. The hemolytic activity of both micellar structures against rat red blood cells was also measured. The results showed the formation of SN-38-polymeric micellar conjugates at diameters < 50 nm with a narrow size distribution and sustained release of SN-38 for both structures. The loading content of SN-38 in mPEO-b-PBCL and mPEO-b-PCCL were 11.47 ± 0.10 and 12.03 ± 0.17 (% w/w), respectively. The mPEO-b-PBCL/SN-38, end-capped micelles were kinetically more stable than mPEO-b-PCCL/SN-38. The self-assembled mPEO-b-PBCL/SN-38 and mPEO-b-PCCL/SN-38 micelles resulted in significantly higher cytotoxic effects than irinotecan against human colorectal cancer cell lines HCT116, HT-29, and SW20. The CRC cells were found to be 70-fold to 330-fold more sensitive to micellar SN-38 than irinotecan, on average. Both SN-38-incorporated micelles showed two-fold higher caspase-3/7 activation levels than irinotecan. The mPEO-b-PBCL/SN-38 micelles were not hemolytic, but mPEO-b-PCCL/SN-38 showed some hemolysis. The overall results from this study uphold mPEO-b-PBCL/SN-38 over mPEO-b-PCCL/SN-38 micellar formulation as an effective delivery system of SN-38 that warrants further preclinical investigation.

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