Developing Nanoceria-Based pH-Dependent Cancer-Directed Drug Delivery System for Retinoblastoma.

Development of a single combinatorial nano-platform technology to target cancer cells has been an unprecedented reality in boosting synergistic anti-tumor activities and in reducing off-target effects. We have designed a novel anti-tumor delivery system using a chemotherapy drug and a tumor target molecule covalently linked to cerium oxide nanoparticles (nanoceria). Nanoceria have a unique redox activity in that they possess antioxidant activity at physiological pH but have an intrinsic oxidase activity at acidic pH.

Nanoceria-loaded injectable hydrogels for potential age-related macular degeneration treatment.

The major purpose of this article is to evaluate oligochitosan coated cerium oxide nanoparticles (OCCNPs) alginate laden injectable hydrogels and their potential treatment for age-related macular degeneration (AMD). The water soluble OCCNPs were loaded within injectable hydrogels as antioxidative agents. The release of OCCNPs from hydrogel, radical scavenging properties, and biocompatibility were evaluated and calculated in vitro.

Genomic form of rhodopsin DNA nanoparticles rescued autosomal dominant Retinitis pigmentosa in the P23H knock-in mouse model.

Retinitis pigmentosa (RP) is a group of inherited retinal degenerative conditions and a leading cause of irreversible blindness. 25%-30% of RP cases are caused by inherited autosomal dominant (ad) mutations in the rhodopsin (Rho) protein of the retina, which impose a barrier for developing therapeutic treatments for this genetically heterogeneous disorder, as simple gene replacement is not sufficient to overcome dominant disease alleles. Previously, we have explored using the genomic short-form of Rho (sgRho) for gene augmentation therapy of RP in a Rho knockout mouse model.

Nanoparticle-mediated miR200-b delivery for the treatment of diabetic retinopathy.

We recently reported that the Ins2(Akita) mouse is a good model for late-onset diabetic retinopathy. Here, we investigated the effect of miR200-b, a potential anti-angiogenic factor, on VEGF receptor 2 (VEGFR-2) expression and to determine the underlying angiogenic response in mouse endothelial cells, and in retinas from aged Ins2(Akita) mice. MiR200-b and its native flanking sequences were amplified and cloned into a pCAG-eGFP vector directed by the ubiquitous CAG promoter (namely pCAG-miR200-b-IRES-eGFP).

Nanoparticle-motivated gene delivery for ophthalmic application.

Ophthalmic gene therapy is an intellectual and intentional manipulation of desired gene expression into the specific cells of an eye for the treatment of ophthalmic (ocular) genetic dystrophies and pathological conditions. Exogenous nucleic acids such as DNA, small interfering RNA, micro RNA, and so on, are used for the purpose of managing expression of the desired therapeutic proteins in ocular tissues. The delivery of unprotected nucleic acids into the cells is limited because of exogenous and endogenous degradation modalities.

Antimicrobial activity, biocompatibility and hydrogelation ability of dipeptide-based amphiphiles.

The development of new antibiotics is of increasing importance due to the growing resistance power of microbes against conventional drugs. To this end, cationic peptides are emerging as clinically potent antimicrobial agents. In the present study, we have synthesized six dipeptide-based cationic amphiphiles with different head group structures by varying combinations of l-amino acid residues.

Structure and properties of low molecular weight amphiphilic peptide hydrogelators.

The search for low molecular weight hydrogelators (LMWH) with varying structural motif is getting intense because of its potential application in the field of biomedicines as well as the diversified area of nano-biotechnology. In this paper, we have developed hydrogels of simple cationic dipeptide amphiphiles that have a wide range of minimum gelation concentration (MGC), 12-0.25% (w/v) in plain water.

Asymmetric resolution in ester reduction by NaBH4 at the interface of aqueous aggregates of amino acid, peptide, and chiral-counterion-based cationic surfactants.

This study provides insight into the physicochemical aspects of aqueous aggregates that comprise amino acid, peptide, and chiral-counterion-based cationic surfactants and their correlation with the proficiency of asymmetric resolution in ester reduction. The effects of the structural differences in the naturally occurring amino acid based and synthetic chiral-counterion-containing gemini surfactants on the surface properties as well as on other microstructural parameters were studied and correlated to the varied head groups of the surfactants. The supramolecular chirality induced from the head-group region of chiral amphiphiles in aqueous self-aggregates is evident from circular dichroism, scanning electron microscopy, and transmission electron microscopy studies.

Effect of counterions on the activity of lipase in cationic water-in-oil microemulsions.

This paper delineates how the different counterions affect the physicochemical properties of the aqueous aggregates and thereby the lipase activities at the interface of cationic water-in-oil microemulsions. To this end, we have synthesized a series of cetyltrimethylammonium-based surfactants, 1-14, having aliphatic, aliphatic with aromatic substitution at the alpha position, and aromatic carboxylate anion as the counterion. The physicochemical characterizations of these aqueous aggregates were done by conductometric, tensiometric, fluorometric techniques to determine counterion binding (beta), critical micelle concentration (cmc), and micropolarity at the microenvironment.

Water gelation of an amino acid-based amphiphile.

The water immobilization by a simple amino acid-containing cationic surfactant was investigated. A variety of techniques, such as (1)H NMR spectroscopy, circular dichroism (CD), steady-state fluorescence spectroscopy, and field-emission scanning electron microscopy (FESEM) were applied to determine the formation and architecture of the hydrogel. The new gelator with a minimum gelation concentration (MGC) of 0.

Geometric constraints at the surfactant headgroup: effect on lipase activity in cationic reverse micelles.

The primary objective of the present article is to understand how the geometric constraints at the surfactant head affect the lipase activity in the reverse micellar interface. To resolve this issue, surfactants were designed and synthesized, and activity was measured in /water/isooctane/n-hexanol reverse micellar systems at z ([alcohol]/[surfactant])=5.6, pH 6.

Amino Acid based cationic surfactants in aqueous solution: physicochemical study and application of supramolecular chirality in ketone reduction.

The present study provides a molecular understanding of the origin of the chirality in aqueous micelles and its correlation with the proficiency of stereoselective ketone reduction. The effects of varied headgroup architecture on the surface-active properties as well as on other microstructural parameters were studied and correlated to the structural differences of these naturally occurring amino acid containing surfactants (1-4). Micropolarity sensed by pyrene showed that the micelles prepared using 1-4 are mostly hydrated; particularly large headgroup size surfactant produces more polar environment.

Surfactant tail length-dependent lipase activity profile in cationic water-in-oil microemulsions.

The catalytic activity of Chromobacterium viscosum lipase (CV-lipase) was estimated across varying surfactant tail lengths (C-10-C-18) in water-in-oil (w/o) microemulsions of cationic surfactants containing four different hydroxyethyl-substituted head groups. An attempt to find a correlation, if any, between the activity of interfacially solubilized lipase and the varying surfactant tails was made for the first time in micellar enzymology. The second-order rate constant, k2, in lipase-catalyzed hydrolysis of p-nitrophenyl-n-hexanoate at pH 6.

Head-group size or hydrophilicity of surfactants: the major regulator of lipase activity in cationic water-in-oil microemulsions.

To determine the crucial role of surfactant head-group size in micellar enzymology, the activity of Chromobacterium Viscosum (CV) lipase was estimated in cationic water-in-oil (w/o) microemulsions of three different series of surfactants with varied head-group size and hydrophilicity. The different series were prepared by subsequent replacement of three methyl groups of cetyltrimethylammonium bromide (CTAB) with hydroxyethyl (1-3, series I), methoxyethyl (4-6, series II), and n-propyl (7-9, series III) groups. The hydrophilicity at the polar head was gradually reduced from series I to series III.