INTRODUCTION:

Nanoscience endeavours to understand materials at the nanoscale level (1-100nm in diameter) and nanotechnology seeks to synthesize, modify and manipulate matter at this level.¹ For the past 30 years, the explosive growth of nanotechnology has brought challenging innovations in the field of pharmacy. As asserted by different authors, nanoparticulated systems show promise as active vectors due to their capacity to release drugs²; their sub cellular size allows relatively higher intracellular uptake than other particulate system³; they can improve the stability of active substances⁴ and can be biocompatible with tissues and cells when synthesized from materials that are either biocompatible or biodegradable.⁵

Nanoparticles are defined as solid, submicron-sized drug carriers that may or may not biodegradable.^6,7 Depending upon the method of preparation, nanosphere or nanocapsules can be obtained. Nanospheres are matrix system in which drug is uniformly dispersed, while nanocapsules are the systems in which the drug is surrounded by a unique polymer membrane. In recent years polymeric nanoparticles have been used as potential drug delivery devices because of their ability to circulate the drug for a prolonged period of time and their ability to deliver proteins, peptides and gene.^8-10

The major goals in designing nanoparticles are to control particle size, surface properties and release of pharmacologically active agent to the specific site.¹¹Overall, the challenge of increasing a drug’s therapeutic effect, with a concurrent minimization of side effects can be optimized through proper design and drug delivery system engineering.^12-14 Depending on the physicochemical characteristics of a drug it is possible to achieve an efficient entrapment of drug by choosing the best method of preparation and the best polymer. The present review focuses on various methods of preparation, characterization and applications of nanoparticulate delivery system.

METHODS OF PREPARATION:

Nanoparticles can be prepared from materials such as proteins, polysaccharides and polymers. The factors influencing the selection of matrix are size of nanoparticles, surface characteristics and inherent properties of drugs, degree of biodegradability and biocompatibility and toxicity. Several methods have been developed for preparing nanoparticles. These methods can be classified into two categories based on whether the formulation requires a polymerization reaction or is achieved directly from a macromolecule or preformed polymer.^6,7

NANOPARTICLES OBTAINED BY POLYMERIZATION OF A MONOMER:

Emulsion polymerization:

Emulsion polymerization is one of the rapid methods for nanoparticles preparation.¹⁵ The method is classified into two categories, based on the use of organic or aqueous continuous phase. The continuous organic phase process involves the dispersion of monomers into an emulsion or into a material in which the monomer is not soluble. Polyacrylamide nanospheres are produced by this method.^16,17 In the early stages of polymerization surfactants or protective soluble polymers are used to prevent aggregation.¹⁸ Example of drugs encapsulated by this system are triamcinolone,¹⁹ pilocarpine²⁰ and timolol. This process has become less important due to toxic organic solvents, monomers and surfactant.

In aqueous continuous phase monomer is dissolved in an aqueous solution and here surfactants or emulsifier are not used. The initiation of polymerization process occurs when a monomer molecule dissolved in the continuous phase with an initiator molecule that might be free radical or ion. Phase separation and formation of solid particles can take place before or after termination of the polymerization.^{21, 22}

Interfacial polymerization:

Poly (alkyl cyanoacrylate) nanoparticles are prepared when cyanoacrylate monomer and drug are dissolved in a mixture of oil and absolute ethanol.²³ The mixture is extruded slowly through a needle into an aqueous solution with continuous stirring. The resulting colloidal suspension can be concentrated by evaporation.

NANOPARTICLES OBTAINED FROM PREFROMED POLYMERS:

Nanoprecipitation:

The nanoprecipitation method is also termed as solvent displacement or interfacial deposition. This method is based on emulsification of the organic internal phase consisting of dissolved polymer into aqueous external phase.^24,25 The polymer is dissolved in water miscible solvent which is then injected into a aqueous solution containing a stabilizer as surfactant with continuous stirring. Polymer deposition occurs between the water and the organic solvent interface due to fast diffusion of solvent, leads to the formation colloidal suspension.²⁶ The key variables of this process are organic phase injection rate, aqueous phase agitation rate and the organic phase/aqueous ratio.

Emulsion diffusion:

Emulsion diffusion method allows for both lipophilic and hydrophilic active substance nanoencapsulation.²⁶ The encapsulating polymer is dissolved in a partially water soluble solvent and saturated with water. The polymer-water saturated solvent phase is emulsified in an aqueous solution containing stabilizer, leading to solvent diffusion to the external phase and formation of nanocapsules or nanospheres. Finally, the solvent is eliminated by filtration or evaporation. Several advantages of this technique are high encapsulation efficiency (generally >70%), ease of scale-up, batch-to-batch reproducibility and narrow size distribution.²⁶ Various drug-loaded nanoparticles are produced by this method, including Plasmid DNA-loaded PLA nanoparticles,²⁷ Indocyamine²⁸ and Coumarin-loaded PLA nanoparticles.²⁹

Emulsification-solvent evaporation:

In emulsion-solvent evaporation technique, the polymer and drug is dissolved in an organic solvent like chloroform, ethyl acetate or dichloromethane. The mixture of drug and polymer is emulsified in an aqueous solution containing surfactant or emulsifying agent to form O/W emulsion. After the formation of emulsion, the organic solvent is evaporated either by means of continuous or by reducing the pressure.³⁰To produce small particle size often ultrasonication or high speed homogenization may be employed.³¹ However, this method can be applied to liposoluble drugs, and limitations are imposed by the scale-up of the high energy requirements in homogenization. Frequently used polymers are PLGA, ethyl cellulose, cellulose acetate phthalate, poly (ε-caprolactone) etc.

Emulsification-reverse salting out:

Emulsification-reverse salting out method can be considered as a modification of the emulsification-solvent diffusion method. The main difference is the composition of the emulsion. The emulsion is formulated with a polymer solvent which is normally totally miscible with water, i.e. acetone.³² Polymer and drug are initially dissolved in a solvent (acetone) which is emulsified into an aqueous gel containing salting out agent (electrolytes like, magnesium chloride, calcium chloride, sucrose etc.) and a stabilizer such as PVP or hydroxyethyl cellulose. The nanosphere is obtained when oil/water emulsion is diluted with sufficient water to enhance the diffusion of acetone in the aqueous phase.²⁶

CHARACTERIZATION OF NANOPARTICLES:

A good physicochemical understanding of the formulation is an absolute necessity for rational formulation design and properly interpreting in vivo results. The nanoparticles are characterized for particle size, surface characteristics, drug carrier interaction and drug release study. Different parameters and characterization methods for nanoparticles are given in Table 1.

Table1. Various parameters and characterization methods for nanoparticles.³³

Parameters	Characterization methods
Particle size and size distribution	Scanning electron microscopy (SEM) Photon correlation spectroscopy, Transmission electron microscopy (TEM), Atomic force microscopy (AFM), Mercury porositometry. Laser defractrometry
Surface hydrophobicity	Water contact angle measurements, Rose bangle (dye) binding, hydrophobic interaction chromatography, X-ray photoelectron microscopy.
Charge determination	Laser droplet anemometry, Zeta potentiometer
Drug-carrier interaction	Differential scanning calometry, FTIR
Release study	In vitro release study under physiologic and sink condition
Drug stability	Bioassay of drug

Table2. Various applications of nanomedicines for the health care.^37-41

Application of nanomedicines	Nanomaterials Name and Type	Pharmacological function	Diseases
Nanomedicines in clinic	Liposome ( 30 – 100 nm)	Targeted drug delivery	Cancer
Nanomedicines in clinic	Nanoparticles (Iron oxide, 5-50 nm)	Contrast agent for magneting resonance imaging	Hepatic (Liver)
Nanomedicines under development	Dendrimers (5 -50 nm)	Contrast agent for magneting resonance imaging	Cardiovascular phase – III clinical trial
	Fullerenes ( Carbon bucky ball 2 -20 nm)	Antioxidant	Neurodegenerative, Cardiovscular
	Nanoshells (Gold-coated silica 60 nm)	Hyperthermia	Cancer preclinical

APPLICATION OF NANOPARTICLES:

Nanomedicine uses nano-sized tools for the diagnosis, prevention and treatment of disease and to gain increased understanding of the complex underlying pathophysiology of disease. The aim of nanomedicine may be broadly defined as the comprehensive monitoring, repairing and improvement of all human biological systems, working from the molecular level using engineered devices and nanostructures to achieve medical benefit.³⁴ Nanomedicine can offer impressive resolutions for various life threatening diseases like cancer, diseases of the cardiovascular system, the lungs, blood, neurological (especially neurodegenerative) diseases, diabetes, inflammatory/ infectious diseases, Parkinson’s or Alzheimer’s disease and orthopaedic problems.^35,
36 Application of nanoparticles are given in table 2.

CONCLUSION:

In current scenario nanoparticles are one of the novel drug delivery systems that can be used for controlling and targeting drug delivery as well as in the field of cosmetics, paints and textiles. As poorly soluble drugs are increasing, therefore, nanoparticles will overcome the problems associated with the formulation of those drugs. US FDA has approved some nanoparticles based drugs and several others are under development.

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Received on 19.01.2011 Modified on 24.02.2011

Research J. Pharm. and Tech. 4(7): July 2011; Page 1016-1019