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OPHTHALMIC NANOPARTICLES DRUG DELIVERY SYSTEMS

OPHTHALMIC NANOPARTICLES DRUG DELIVERY SYSTEMS

Kamal Singh Rathore1, S.S.Sisodia2, M.S.Ranawat2, R.K.Nema3

1B.N. Girls College of Pharmacy, Udaipur

2B.N. College of Pharmacy, Udaipur

3Rishiraj College of Pharmacy, Indore-MP

INTRODUCTION

Nanoparticles are defined as particulate dispersions or solid particles with a size in the range of 10-1000nm. The drug is dissolved, entrapped, encapsulated or attached to a nanoparticle matrix. Depending upon the method of preparation, nanoparticles, nanospheres or nanocapsules can be obtained.

The major goals in designing nanoparticles as a delivery system are to control particle size, surface properties and release of pharmacologically active agents in order to achieve the site-specific action of the drug at the therapeutically optimal rate and dose regimen. Though liposomes have been used as potential carriers with unique advantages including protecting drugs from degradation, targeting to site of action and reduction toxicity or side effects, their applications are limited due to inherent problems such as low encapsulation efficiency, rapid leakage of water-soluble drug in the presence of blood components and poor storage stability. On the other hand, polymeric nanoparticles offer some specific advantages over liposomes. For instance, they help to increase the stability of drugs/proteins and possess useful controlled release properties.

  Advantages of using nanoparticles as a drug delivery system include the      following:

• Particle size and surface characteristics of nanoparticles can be easily manipulated to achieve both passive and active drug targeting after parenteral administration.
• They control and sustain release of the drug during the transportation and at the site of localization, altering organ distribution of the drug and subsequent clearance of the drug so as to achieve increase in drug therapeutic efficacy and reduction in side effects.
• Controlled release and particle degradation characteristics can be readily modulated by the choice of matrix constituents. Drug loading is relatively high and drugs can be incorporated into the systems without any chemical reaction; this is an important factor for preserving the drug activity.
• Site-specific targeting can be achieved by attaching targeting ligands to surface of particles or use of magnetic guidance.
• The system can be used for various routes of administration including oral, nasal, parenteral, intra-ocular etc.
   

In spite of these advantages, nanoparticles do have limitations. For example, their small size and large surface area can lead to particleparticle aggregation, making physical handling of nanoparticles difficult in liquid and dry forms. In addition, small particles size and large surface area readily result in limited drug loading and burst release. These practical problems have to be overcome before nanoparticles can be used clinically or made commercially available. The present review details the latest development of nanoparticulate drug delivery systems, surface modification issues, drug loading strategies, release control and potential applications of nanoparticles.

 

Preparation of nanoparticles Methods:

Nanoparticles can be prepared from a variety of materials such as proteins, polysaccharides and synthetic polymers. The selection of matrix materials is dependent on many factors Including,

• Size of nanoparticles required.
• Inherent properties of the drug, e.g., aqueous solubility and stability.
• Surface characteristics such as charge and permeability.
• Degree of biodegradability, biocompatibility and toxicity.
• Drug release profile desired.
• Antigenicity of the final product.

Methods:

• Dispersion of preformed polymers
• Solvent evaporation method
• Spontaneous emulsification or solvent diffusion Method
• Polymerization method
• Coacervation or ionic gelation method
• Production of nanoparticles using supercritical fluid

 POLY METHYL METHACRYLATE (PMMA) (ACRYLIC)

Molecular formula    (C5O2H8)n
INTRODUCTION
Poly (methyl methacrylate) (PMMA) poly (methyl 2-methylpropenoate) is a thermoplastic and transparent plastic. Chemically, it is the synthetic polymer of methyl methacrylate. PMMA is often used as an alternative to glass, and in competition with polycarbonate (PC). It is often preferred because of its moderate properties, easy handling and processing, and low cost, but behaves in a brittle manner when loaded, especially under an impact force. Acrylic, or acrylic fiber, can also refer to polymers or copolymers containing poly acrylonitrile. The material was developed in 1928 in various laboratories and was brought to market in 1933 by Rohm and Haas Company.

Trade names:

Plexiglas, Vitroflex, Limacryl, R-Cast, Per-Clax, Perspex, Plazcryl, Acrylex, Acrylite, Acrylplast, Altuglas, Polycast, Oroglass and Lucite and is commonly called acrylic glass, simply acrylic or plexiglas.
Other names:  Methyl Methacrylate resin
PHYSICAL AND MECHANICAL PROPERTIES
General physical properties
PMMA is a glassy polymer with an amorphous structure. It has a density of 1.19 g/cm3 and has very low water absorption. The refractive index ranges from 1.49 to 1.51 depending on the type.

Mechanical properties
Parts made of PMMA have high mechanical strength and good dimensional stability. PMMA is one of the hardest thermoplastics and is also highly scratch resistant.

THERMAL, ELECTRICAL AND OPTICAL PROPERTIES
Heat-stabilized types can withstand temperatures of up to 100oC. PMMA can withstand temperatures as low as -70oC. Resistance to temperature changes is very good. Glass transition temperature of PMMA is in the range of 100-120C.

Fire behavior
PMMA ignites very quickly. It burns with a blue glow, even outside the flame, and crackles with white spurts.

•   Electrical properties
  PMMA has good insulating properties, a high dielectric strength and high tracking resistance. The relatively high surface resistance, however, encourages electrostatic charges on the surface of moulded parts; this can be largely overcome by the use of antistatic agents.
• Optical properties
  PMMA is naturally transparent and colourless. The transmission for visible light is 92%. The refractive index is 1.492 for PMMA. There are types that transmit UV rays, and types that absorb it almost completely, as a result of which sensitive dyes on painted surfaces behind are protected from fading.
• Chemical Resistance Properties
  PMMA is resistant to aliphatic hydrocarbons, cycloaliphatic compounds, fats and oils, and also to dilute acids at temperatures of up to 60oC. Chlorinated aliphatic hydrocarbons, ketones, alcohols, ethers, esters, aromatics, petrol, spirit, nitrocellulose varnishes and certain plasticisers cause PMMA to swell or produce stress cracks.  The resistance to weathering of PMMA is very good.

Natural colour
PMMA is crystal clear and has a high surface gloss. It can be produced in all colours, transparent and muted.

Health and Safety
PMMA is odorless and tasteless and physiologically safe.

USES
PMMA or Acrylic is a versatile material and has been used in a wide range of fields and applications.

Medical technologies and implants
PMMA has a good degree of compatibility with human tissue, and can be used for replacement intraocular lenses in the eye when the original lens has been removed in the treatment of cataracts. Historically, hard contact lenses were frequently made of this material. Soft contact lenses are often made of a related polymer, where acrylate monomers containing one or more hydroxyl groups make them hydrophilic.
In orthopedics, PMMA bone cement is used to affix implants and to remodel lost bone. It is supplied as a powder with liquid methyl methacrylate (MMA). Although PMMA is biologically compatible, MMA is considered to be an irritant and a possible carcinogen. PMMA has also been linked to cardiopulmonary events in the operating room due to hypotension. Bone cement acts like a grout and not so much like a glue in arthroplasty. Although sticky, it does not bond to either the bone or the implant, it primarily fills the spaces between the prosthesis and the bone preventing motion.
Dentures are often made of PMMA, and can be colour-matched to the patient's teeth & gum tissue. In cosmetic surgery, tiny PMMA microspheres suspended in some biological fluid are injected under the skin to reduce wrinkles or scars permanently.

ADVANTAGES AND LIMITATIONS
 

Advantages
1. Material is very hard.

2. Material is clear and can be coloured in any colour from opaque to translucent.

3. Good weathering resistance

4. Good optical properties.

5. High gloss.

6. Scratch resistant (but not as good as glass because it does scratch - this is why car wind   screens are not made from PMMA).

Limitations

1. Brittle under impact conditions and failure is by shattering.

2. Difficult to mould thin walled products because of poor flow properties.

3. Poor hot-melt strength limits processing methods.

4. Flow properties make processing slow compared to other materials.

5. Does not have significant elastic deformation before failure i.e. goes straight to brittle fracture.

 

REFERENCES

1. Alonso MJ, Sánchez A. Biodegradable nanoparticles as new transmucosal drug carriers. Sönke Svenson eds. Carrier-Based Drug Delivery. 2004; 283–295. ACS Symposium Series Washington DC.
2. Calvo P, Sánchez A, Martínez J, et al. Polyester nanocapsules as new topical ocular delivery systems for cyclosporine A. Pharmacol Res. 1996;13:311–315.
3.  Calvo P, Thomas C, Alonso MJ, Vila-Jato JL, Robinson JR. Study of the mechanism of interaction of poly-e-caprolactone nanocapsules with the cornea by confocal laser scanning microscopy. Int J Pharmacol. 1994; 103:283–291.
4. Harmia T, Speiser P, Kreuter J. A solid colloidal drug delivery system for the eye: encapsulation of pilocarpin in nanoparticles. J Microencapsulation. 1986; 3:3–12.
5. Hirano S, Seino H, Akiyama I, Nonaka I. Chitosan: a biocompatible material for oral and intravenous administration. Gebelein CG Dunn RL eds. Progress in Biomedical Polymers. 1990; 283–289. Plenum Press New York.
6. Losa C, Calvo P, Vila-Jato JL, Alonso MJ. Improvement of ocular penetration of a amikacin sulphate by association to poly-(butylcyanoacrylate) nanoparticles. J Pharm Pharmacol. 1991; 43:548–552.
7.  Losa C, Marchal-Heussler L, Orallo F, Vila-Jato JL, Alonso MJ. Design of new formulations for topical ocular administration: polymeric nanocapsules containing metipranolol. Pharmacol Res. 1993; 10:80

 

 

About the Author

Kamal Singh Rathore, Reader,
B.N. Girls College of Pharmacy, Udaipur-313002 INDIA
e-mail:kamalsrathore@gmail.com;k_mail123@rediffmail.com
Mobile:+919828325713

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