Venkat Vaibav Reddy

8/13/2019 Venkat Vaibav Reddy

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NANOGELS AS DRUG DELIVERY CARRIERS

Y.Venkata Vybhav Reddy1*,K.Rama Krishna1, B.Sowjanya Battu2, Dr.V Uma Maheswara Rao3.

1. IV/ IV B.Pharmacy,Dept.of Pharmaceutics, CMR College of pharmacy, Hyderabad, A.P,India.2.Asst. prof., Dept. of Pharmaceutics, CMR College of pharmacy, Hyderabad, A. P, India.

3. Principal, Dept. of Pharmacognosy, CMR College of pharmacy, Hyderabad, A. P, India

Introduction:Nanotechnologies are materials and devices that have a functional

organization in at least one dimension on the nanometer (one billionth of a meter) scale,

ranging from a few to about 100 nanometers. Nanoengineered materials and devices aimed at

biologic applications and medicine in general, and neuroscience in particular, are designed

fundamentally to interface and interact with cells and their tissues at the molecular level. Thepotential of nanotechnological applications to biology and medicine arise from the fact that they

exhibit bulk mesoscale and macroscale chemical and/or physical properties that are unique to

the engineered material or device and not necessarily possessed by the molecules alone.


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Figure 1: Electron microscopical images of various nanoparticles3


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An ability to cross the blood-brain barrier (BBB) to deliver drugs

or other molecules (for example, oligonucleotides, genes, or contrast agents) while potentially

targeting a specific group of cells (for instance, a tumor) requires a number of things to happen

together. Ideally, a nanodelivery-drug complex would be administered systemically (for example,intravenously) but would find the CNS while producing minimal systemic effects, be able to cross

the BBB and correctly target cells in the CNS, and then carry out its primary active function, such

as releasing a drug. These technically demanding obstacles and challenges will require

multidisciplinary solutions between different fields, including engineering, chemistry, cell

biology, physiology, pharmacology, and medicine. Successfully doing so will greatly benefit the

patient. Although this ideal scenario has not yet been realized, a considerable body of work hasbeen done to develop nanotechnological delivery strategies for crossing the BBB.

This supports the development of nanotechnologies that can potentially carry out

multiple specific functions at once or in a predefined sequence, which is an importantproperty for the clinically successful delivery of drugs and other molecules to the central

nervous system (CNS).


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Figure2:-The blood-brain barrier;above, cross section through the brain;center, schematic representation of the BBB;below,

cellular structure.


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NANOGEL CHARACHTERIZATION:

For analysis of PEG/PEI ratio in nanogel preparations,

5% solutions of dried nano-PEG-cross-PEI samples in D2O were prepared and filtered.1H NMR

spectra (with integration) were measured in the range 06 ppm at ambient temperature using

the Varian 300 MHz spectrometer. Elemental analysis (MH-W Laboratories, Phoenix, AZ) wasused to measure total nitrogen content in nanogel preparations. The amount of ionizable

groups in nanogel was determined by potentiometric titration of 1% suspension in 0.15 M

solution of sodium chloride with hydrochloric acid. Before analysis, nanogel samples were

dialyzed in 2% aqueous ammonia for 24 h and then lyophilized.

Result:FLOUROSCENCE MICROSCOPIC STUDIES:Localization of ODN and nanogel following their uptake in BBMEC monolayers for 2 h was

examined by laser confocal fluorescent microscopy. These experiments used FITC-labeled

ODN and RITC-labeled nanogel to visualize both components within the cell. Typical

micrographs are presented in Figure 1. All three images are recorded from the same sample


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Panel A shows the localization of FITC-ODN. Panel B shows the

localization of RITC- nanogel. Panel C is the superposition of images A and B displaying

localization of both ODN and nanogel. Fluorescein label (ODN) was mainly spread throughout

the cells with significant portion displayed in what appears to be cytoplasmic compartments

(panel A). Similar cytoplasmic localization was displayed in the case of the rhodamine label

(nanogel) (panel B). In the superposed images the areas of colocalization of ODN and nanogelare evident by yellow and orange colors (panel C). However, this panel also clearly shows that in

selected cells a portion of fluorescein label is displayed in the nucleus, while practically no

rhodamine fluorescence was found in the nucleus.


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Stability of Nanogel in Serum:To examine the protection of ODN against nuclease degradation the free ODN or

nanogel-ODN complexes were incubated in freshly prepared mouse serum. As is seen

in Figure2, after 1 h incubation in serum substantial amount of free ODN was degraded

(compare panels A and C). In contrast ODN incorporated in nanogel displayed little if any

degradation (panels B and D).

FIG:(2) FIG:(3)


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ConclusionsA novel ODN delivery system based on positively charged nanosized

hydrogel particles, nano-PEG-cross-PEI, has been developed. The ODN-loaded nanogel

remains stable in dispersion due to the solubilizing effect of nonionic hydrophilic PEG chains

resulting in a formation of nanosized particles. Nanogel structure enables easy attachment of

vector groups for targeted delivery. In particular, nanogel carriers vectorized with insulin and

transferrin molecules were shown to efficiently deliver antisense ODN across BBB as

demonstrated using a cell model, BBMEC. Following transport across the brain microvessel

endothelial cells a significant portion of ODN remained associated with nanogel. Nanogel

carriers have low toxicity, especially in the loaded form, and show no adverse toxic effect

being injected intravenously in mice. Further studies in vivo should reveal the potential for theuse of the vectorized nanogel carriers for systemic delivery of antisense ODN into the brain.

Acknowledgment:.

The studies were supported in parts by grants from National Science Foundation (BES

9986393) and National Institutes of Health (NS 366229) awarded to A.V.K.NanoGel is atrademark of Supratek Pharma Inc. (Montreal, Canada), who supported part of the work on

synthesis of the nanogel material. A.V.K. is a cofounder and consultant for this company.

The authors would like to acknowledge the technical assistance of Shu Li in performing of

the transport studies on BBMEC mono-layers.


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