Synthesis of novel cationic bolaamphiphiles from vernonia oil and their aggregated structures

Grinberg, Sarina; Kolot, V. N.; Linder, Charles; Shaubi, Eleonora; Kas’yanov, V.; Deckelbaum, Richard J.; Heldman, Eli

doi:10.1016/j.chemphyslip.2008.01.006

Cited by 40 publications

(36 citation statements)

References 25 publications

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“…The ACh head groups of GLH-20 were previously shown by us to be hydrolyzed by AChE. 16 In order to compare the hydrolysis rate of GLH-20's head group to a similar ACh head group of a bolaamphiphile with a longer alkyl chain pendant adjacent to the ACh head group, we had to synthesize a novel bolaamphiphile with the required features. We used oleic acid to synthesize the new bolaamphiphile, which was named GLH-32 ( Figure 1).…”

Section: Results and Discussion Synthesis Of Bolaamphiphilesmentioning

confidence: 99%

“…GLH-20 was synthesized from vernonia oil (containing about 70% vernolic acid with naturally occurring epoxy groups), 30 that was obtained from Ver Tech International (Rockville, MD, USA), according to the procedure described by us previously. 16 synthesis of glh-32 synthesis of 9,10-epoxy methyl stearate (1) Methyl oleate (Sigma-Aldrich, purity 99%) was used as received. Ti-MCM-41 (1.8 wt% Ti) was prepared as described previously, 31 and calcinated at 773 K under dry air before use.…”

Section: Materials and Methods Materialsmentioning

confidence: 99%

“…There are, however, continued efforts to develop improved liposomes that release their encapsulated drug as a result of a triggering event, such as increased temperature, [8][9][10] changes in pH, 11 alternating magnetic field, 12 exposure to light, 13 and exposure to specific enzymes. [14][15][16] However, all these approaches involve DDSs in which the release rate is not controlled. There is a need for DDSs that will release drugs at their site of action at a desired rate, which would vary depending on the encapsulated drug and the medical indication treated by the drug.…”

Section: Introductionmentioning

confidence: 99%

“…19,20 Indeed, vesicles made from a variety of bolaamphiphiles have been prepared for various applications, such as for molecular recognition, 21 controllable release, 22 targeted drug delivery, and imaging. 23 Recently, we have described novel nanovesicles made of synthetic bolaamphiphiles with acetylcholine (ACh) head groups 16,24 that are capable of releasing their encapsulated content upon exposure to acetylcholinesterases (AChEs). [25][26][27] When AChE hydrolyzes the ACh surface groups of such vesicles, the vesicular structure is disrupted, resulting in a release of the encapsulated material.…”

Section: Introductionmentioning

confidence: 99%

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Steric environment around acetylcholine head groups of bolaamphiphilic nanovesicles influences the release rate of encapsulated compounds

Stern¹,

Shaubi²,

Popov³

et al. 2014

IJN

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Two bolaamphiphilic compounds with identical acetylcholine (ACh) head groups, but with different lengths of an alkyl chain pendant adjacent to the head group, as well as differences between their hydrophobic skeleton, were investigated for their ability to self-assemble into vesicles that release their encapsulated content upon hydrolysis of their head groups by acetylcholinesterase (AChE). One of these bolaamphiphiles, synthesized from vernolic acid, has an alkyl chain pendant of five methylene groups, while the other, synthesized from oleic acid, has an alkyl chain pendant of eight methylene groups. Both bolaamphiphiles formed stable spherical vesicles with a diameter of about 130 nm. The ACh head groups of both bolaamphiphiles were hydrolyzed by AChE, but the hydrolysis rate was significantly faster for the bolaamphiphile with the shorter aliphatic chain pendant. Likewise, upon exposure to AChE, vesicles made from the bolaamphiphile with the shorter alkyl chain pendant released their encapsulated content faster than vesicles made from the bolaamphiphile with the longer alkyl chain pendant. Our results suggest that the steric environment around the ACh head group of bolaamphiphiles is a major factor affecting the hydrolysis rate of the head groups by AChE. Attaching an alkyl chain to the bolaamphiphile near the ACh head group allows self-assembled vesicles to form with a controlled release rate of the encapsulated materials, whereas shorter alkyl chains enable a faster head group hydrolysis, and consequently faster release, than longer alkyl chains. This principle may be implemented in the design of bolaamphiphiles for the formation of vesicles for drug delivery with desired controlled release rates.

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Section: Results and Discussion Synthesis Of Bolaamphiphilesmentioning

confidence: 99%

Section: Materials and Methods Materialsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Steric environment around acetylcholine head groups of bolaamphiphilic nanovesicles influences the release rate of encapsulated compounds

Stern¹,

Shaubi²,

Popov³

et al. 2014

IJN

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“…We have undertaken to characterize selected RNA carriers both computationally and experimentally. Of special interest to us was a class of lipids called bolaamphiphiles, or bolas, that have been shown to complex with peptides, proteins and plasmid DNAs [135][136][137]. They were also shown to cross cell membranes and are capable of moving across the blood-brain barrier [138].…”

Section: Delivery Of Multifunctional Rna and Dna Nanoparticlesmentioning

confidence: 99%

Triggering RNAi with multifunctional RNA nanoparticles and their delivery

Dao¹,

Viard²,

Martins³

et al. 2015

DNA and RNA Nanotechnology

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in the bloodstream, poor cellular uptake, and inefficient intracellular release. In an attempt to solve these issues, different types of RNAi therapeutic delivery strategies including multifunctional RNA nanoparticles are being developed. In this mini-review, we will briefly describe some of the current approaches.Keywords: RNA nanotechnology, RNA nanoparticles, RNA/DNA hybrids, RNA interference, siRNA, delivery IntroductionAccording to the Social Security Administration, average Americans that reach age 65 today most likely will live to be 84 years old [1]. However, with older age, the chances of contracting deadly diseases, such as cancer, increases dramatically. Some cancers (e.g. breast cancer) can be removed surgically but this does not guarantee that the disease will not return within a patient's lifetime. For other types of cancer (e.g. chronic lymphocytic leukemia), surgery may have very little effect (http://www. cancer.org). Other available treatments are chemo-and immunotherapies. However, these alternatives lack target specificity and cause severe toxic side effects affecting the growth of hair, nails, loss of appetite and blood cell count, just to name a few (http://www.cancer.org). Therefore, the advancements in biomedical technologies that provide safe and effective cancer treatment are in demand. Among the novel approaches is the recognition and use of specific intracellular RNA signatures (e.g. an overexpression of certain genes) that are especially important in detection and personalized treatments of cancers as well as viral infections, and autoimmune diseases [2][3][4]. The wide use of novel therapeutics based on target specific RNA-mediated gene silencing, called RNA interference or RNAi, will likely become the next breakthrough in cancer therapy. The first successful therapeutic knockdown of the endogenous gene, apolipoprotein B (ApoB), occurred in a 2004 study [5], only a few years after the original discovery of RNAi [6]. In 2010, DOI 10.1515/rnan-2015-0001 Received April 6, 2015 accepted May 6, 2015 Abstract: Proteins are considered to be the key players in structure, function, and metabolic regulation of our bodies. The mechanisms used in conventional therapies often rely on inhibition of proteins with small molecules, but another promising method to treat disease is by targeting the corresponding mRNAs. In 1998, Craig Mellow and Andrew Fire discovered dsRNA-mediated gene silencing via RNA interference or RNAi. This discovery introduced almost unlimited possibilities for new gene silencing methods, thus opening new doors to clinical medicine. RNAi is a biological process that inhibits gene expression by targeting the mRNA. RNAi-based therapeutics have several potential advantages (i) a priori ability to target any gene, (ii) relatively simple design process, (iii) sitespecificity, (iv) potency, and (v) a potentially safe and selective knockdown of the targeted cells. However, the problem lies within the formulation and delivery of RNAi therapeutics including rapid excretion, instab...

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Class II major histocompatibility complex–associated response to type XI collagen regulates the development of chronic arthritis in rats

Tuncel¹,

Haag²,

Carlsén³

et al. 2012

Arthritis & Rheumatism

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Objective. Chronic inflammation of the peripheral joints is a hallmark of rheumatoid arthritis (RA). The autoantibody response in RA has been shown to be directed mainly to ubiquitous antigens, whereas the response to cartilage proteins has been less extensively investigated. This study was undertaken to characterize the immune response in pristane-induced arthritis (PIA) in the rat to the cartilage-specific proteins type II collagen (CII) and type XI collagen (CXI) and to genetically fine-map their underlying major histocompatibility complex (MHC) associations.Methods. The genetic control of CII and CXI immunity was mapped using intra-MHC-recombinant inbred strains immunized with the respective collagens. Reactivity with CII and CXI was tested in acute and chronic PIA and in 356 HLA-typed patients with recently diagnosed RA.Results. Mapping of arthritis susceptibility within the MHC region revealed a 144-223-kb locus containing <12 genes, including paralogs for HLA-DQ and HLA-DR. Susceptibility to CII and CXI was linked to haplotypes RT1 av1 (DA) and RT1 f (DA.1F), respectively. After injection of pristane, rats of both strains developed weak T cell and IgG responses to CII, but not to CXI. In chronic arthritis, however, collagen reactivity was stronger, specific for CXI, and restricted to rats with RT1 f MHC. Among RA patients, 12% exhibited a specific IgG response to CXI, 6% to CII, and 6% to both collagens.Conclusion. These findings demonstrate a shift in cartilage recognition in early and chronic arthritis in the rat, suggesting that CXI autoreactivity contributes to the perpetuation of chronic disease. The results provide evidence of the importance of joint antigens in arthritis development.

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Synthesis of novel cationic bolaamphiphiles from vernonia oil and their aggregated structures

Cited by 40 publications

References 25 publications

Steric environment around acetylcholine head groups of bolaamphiphilic nanovesicles influences the release rate of encapsulated compounds

Steric environment around acetylcholine head groups of bolaamphiphilic nanovesicles influences the release rate of encapsulated compounds

Triggering RNAi with multifunctional RNA nanoparticles and their delivery

Class II major histocompatibility complex–associated response to type XI collagen regulates the development of chronic arthritis in rats

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