Use of Core-Shell Nanoparticles in Drug Delivery

Submitted by:

Nikita Gupta

01140801014

M.Tech NST

2nd semester

Introduction

Nanoparticles : any particle that is sized between 1 and 100 nanometers (in terms of diameter). The use of nanoparticles allows one to change the pharmacokinetic properties of the drug without changing the active compound.

General properties of nanoscale particles:1. High surface area to volume ratio.2. Able to interact with biomolecules on the surface of cells3. Able to diffuse through the body well.

Introduction Drug is a chemical substance used in the treatment,

cure, prevention, or diagnosis of disease or used to enhance physical or mental well-being.

Drug Delivery delivering the drug at the right place, at the right concentration for the right period of time. Because of their small sizes, nanoparticles are taken by cells where large particles would be excluded or cleared from the body. Nanoparticles for drug delivery can be metal-, polymer-, or lipid-based.

Types of Drug Delivery

TARGETED DRUG DELIVERY: Delivering a drug  to a specific site in the body where it has the greatest effect, instead of allowing it to diffuse to various sites, where it may cause damage or trigger side effects.

CONTROLLED DRUG DELIVERY: Is one which delivers the drug at a predetermined rate , for locally or systematically , for specified period of time .

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Nano shells - An Introduction

Developed by Drs. Naomi Halas and Jennifer West – Rice University 1994

Nano shells have a core of silica and a metallic outer layer. These nanoshells can be injected safely.

Because of their size, nanoshells will preferentially concentrate in cancer lesion sites. This physical selectivity occurs through a phenomenon called enhanced permeation retention (EPR).

The Nano shells carry molecular conjugates to the antigens that are expressed on the cancer cells themselves or in the tumor microenvironment. This second degree of specificity preferentially links the nanoshells to the tumor and not to neighboring healthy cells.

The most useful Nano shells are those that absorb near infrared light(700nm-1mm) that can easily penetrate Several centimeters in human tissues.

Absorption of light by Nano shells creates an intense heat that is lethal to cells.

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Generally speaking, biocompatible core–shell nanoparticles are composed of a functionalized core, a modifiable shell, and the biomolecules modified on the surface of the nanoparticles as shown in Figure. The three parts all make prominent contributions to their application of biomedicine.

Different Shaped Core/shell Nanoparticles

Figure: Different core/shell nanoparticles:

(a) spherical core/shell nanoparticles;

(b) hexagonal core/shell nanoparticles;

(c) multiple small core materials coated by single shell material;

(d) nanomatryushka(Nano sphere in a shell) material;

(e) movable core within hollow shell material.

The properties of nanoparticles are not only size dependent but are also linked with the actual shape.

For example, certain properties of magnetic nanocrystals such as the blocking temperature, magnetic saturation, and permanent magnetization are all dependent on particle size, but the coercivity of the nanocrystals totally depends on the particle shape because of surface anisotropy effects

Other nanoparticle physical and chemical properties such as catalytic activity and selectivity, electrical and optical properties, sensitivity to surface-enhanced Raman scattering (SERS) and the Plasmon resonance and melting point are also all highly shape-dependent

Importance of Core/Shell Nanoparticles Emerged at the frontier between materials chemistry and many other fields, such as

electronics, biomedical, pharmaceutical, optics, and catalysis.

Core/shell nanoparticles are highly functional materials with modified properties.

Because of the shell material coating, the properties of the core particle such as reactivity decrease or thermal stability can be modified, so that the overall particle stability and dispersibility increases.

The purpose of the coating on the core particle are many fold, such as surface modification, the ability to increase the functionality, stability, and dispersibility, controlled release of the core, reduction in consumption of precious materials, and so on.

Nano- and microsized hollow particles are used for different purposes such as micro vessels, catalytic supports, adsorbents, lightweight structural materials and thermal and electric insulators.

Techniques, Classifications & Mechanism Of Core/Shell Nanoparticle Synthesis

In general, core/shell nanoparticles are synthesized using a two-step process, first synthesis of core and second the synthesis of the shell.

The synthesis techniques of core/shell nanoparticles can be classified into two types depending on the availability of core particles:

(i) the core particles are synthesized and separately incorporated into the system with proper surface modification for coating the shell material;

(ii) the core particles are synthesized in situ, and this is followed by coating of the shell material.

The basic advantage of external core synthesis is the fact that core particles are available in pure form and hence there is less possibility of impurities on the core surface.

Whereas, in situ synthesis, the main problem is that some impurity from the reaction media may be trapped between the core and shell layer.

The most important step during synthesis of core/shell particles is to maintain uniform coating and to control the shell thickness.

Some of the various synthetic methods for core/ shell particles used by different research groups are precipitation, polymerization, micro emulsion, sol-gel condensation, layer by layer adsorption techniques etc.

1) A nanoparticle carries the pharmaceutical agent inside its core, while its shell is functionalized with a ‘binding’ agent

2) Through the ‘binding’ agent, the ‘targeted’ nanoparticle recognizes the target cell. The functionalized nanoparticle shell interacts with the cell membrane

3) The nanoparticle is ingested inside the cell, and interacts with the biomolecules inside the cell

4) The nanoparticle breaks, and the pharmaceutical agent is released

Nanotechnology – based drug delivery Systems

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Nano shells – Curing Tumors

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Nano shells – Curing Tumors

Absorption of light by nanoshells creates an intense heat that is lethal to cells. These are used for early detection of cancer and its treatment by embedding drug containing tumor targeted hydrogel polymer and injected in the body .which when heated with laser (infrared)and thus release drug at tumor site .

PLGA–lecithin–PEG core–shell nanoparticles for controlled drug delivery

The development of biodegradable core–shell NP systems that combined the beneficial properties of liposomal and polymeric NPs for controlled drug delivery. These core–shell NPs are formed from three biomaterials:

(i)Poly(D,L-lactide-co-glycolide) (PLGA) was selected for the hydrophobic core due to its biodegradable nature and have good mechanical properties for drug delivery applications and ability to encapsulate high amounts of hydrophobic drugs(chemotherapeutic drug Dtxl); PLGA is a diblock copolymer. It is capable of carrying highly insoluble drugs with high loading capacity.

(ii) lecithin was chosen for a monolayer around the hydrophobic core;

(iii) Poly(ethylene)glycol(PEG) intersperses in the lecithin monolayer to form a PEG shell which provides electrostatic and steric stabilizations, a longer circulation half-life in vivo as well as functional-end groups for the attachment of targeting ligands such as antibodies, peptides and aptamers.

A modified Nano precipitation technique was used to prepare the NPs. Preparation of the NPs showed that various formulation parameter such as the lipid/polymer mass ratio and lipid/lipid–PEG molar ratio controlled NP physical stability and size.

Preparation of PLGA-lecithin-PEG NPs

DLS was used to characterize NP hydrodynamic size, poly-dispersity and zeta potential in each preparation. The average diameter of synthesized NPs ranged between 60 and 70 nm. The zeta potential ranged between 40 mV and 60 mV, depending on the size and composition of the NPs. Regardless of Dtxl loading, the particle sizes and zeta potentials remained in the same range. A schematic shows the core-shell structure of the NPs, while TEM was used to examine the morphology of the NPs. The TEM images revealed that the NPs are dispersed as individual NPs with a well-defined spherical shape and homogeneously distributed around 60-70 nm in diameter, and that the incorporation of Dtxl did not seem to cause morphological changes.

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Applications

References Encyclopedia of Nanoscience and Nanotechnology, 2004, v.1 & 7.

Handbook of Nanoscience, Engineering, and Technology, 2007.

Handbook of Nanotechnology,Springer,3rd edition.

Nanoparticle technology for drug delivery, volume 159 by Ram B Gupta.

journal homepage : www .elsevier .com /locate /biomaterials

PLGA-lecithin-PEG core-shell nanoparticles for controlled drug delivery by Juliana M. Chan , Liangfang Zhang , Kai P. Yuet , Grace Liao , June-Wha Rhee , Robert Langer , Omid C. Farokhzad.

Wikipedia.

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