AN OVERVIEW ON POLYMERIC NANOPARTICLESUSED IN THE TREATMENT OF DIABETES MELLITUS
K.GOPALASATHEESKUMAR1*, S.KOMALA2 AND M.MAHALAKSHMI2
1KMCH college of Pharmacy, Kovai Estate, Kalapatti Road, Coimbatore-641048, Tamil Nadu, India.
2Jaya College of Paramedical sciences, College of Pharmacy, Thiruninravur, Chennai – 602024, Tamil Nadu, India.
The review was carried out to discuss in detail about the polymeric nanoparticles for diabetic treatment. The diabetes is the chronic metabolic disorder characterized by the deficiency of insulin production. The various treatments are available for the diabetes and the nanoparticles are having the several advantages. The various types of nanoparticles are available for the anti-diabetic drugs; the polymeric nanoparticles are the one of the most commonly used nanoparticles. The polymeric nanoparticles are commonly 10-1000nm in size. The polymeric nanoparticles are formulated by drug with the polymers. The main advantages of the polymeric nanoparticles are the simplest preparation method, targeted delivery, the minimizing of the dose and high therapeutic efficiency. In this review was mainly can be focused on advantages, disadvantages of polymeric nanoparticles, various polymers, various formulation techniques, diabetes disease profile, insulin production, various anti-diabetic drugs and the polymeric nanoparticle formulation of anti-diabetic drugs.
Reference Id: PHARMATUTOR-ART-2549
Nanomedicine is a subdivision of nanotechnology, which uses small particles that are more than 10 million times smaller than the human body. In nano-medicine, these particles are greatlylesser than the living cell. Because of this, nanomedicine presents many innovativechances in the fight against all types of cancer, neurodegenerative disorders and other diseases. (SovanLal et al., 2011)
Liposomes are concentric bilayered vesicles in which an aqueous volume is completelysurrounded by a membranous lipid bilayer mainly composed of natural or synthetic phospholipids. Nanocrystals are aggregates of about hundreds or thousands of particles that combine in a crystal-like form, composed of pure drug with only a thin coating comprised of surfactant or combination of surfactants.(Nishikant et al., 2012, Senthilnathan et al., 2016) Solid Lipid Nanoparticles contain a solid lipid medium, where the drug is normally incorporated, with an average diameter below 1 μm. (Nagarajan et al., 2015) Dendrimers, anexceptional class of polymers, are extremely branched macromolecules whose size andshape can be exactlymeasured. Metallic nanoparticles are the having the metallic compounds like gold, silver, selenium, iron etc. the green synthesized nanoparticles are having the plant source of nanoparticles. (Nagavarma et al., 2012, Mohanraj et al., 2006)
Polymeric nanoparticles are commonly 10-1000nm in dimension. These polymeric nanoparticles are formulated from the polymers, which have the nature of bio-adaptability,bio-comptabilityand bio-degradable. The drug is dissolved, entrapped, encapsulated to a nanoparticle medium. The nanoparticles, nano-spheres or nano-capsules are obtained by depending up on the preparation. In nano-capsule system, the drug is limited to a cavity enclosed by evenpolymer layer, while the nano-shell contains of medium, in which the drug is physically and uniformly dispersed.(Konwar et al., 2013, Neha et al., 2013)
Advantages of polymeric nanoparticles
- Preparation method is easy
- Targeted drug delivery method
- Because of their lesser size Nanoparticles enter small capillary and are taken up through the cell which allows for well-organized drug buildup at the target sites in the body. (Nishikant et al., 2012)
- Good control of over size and size distribution.
- Good protection of the compressed drug.
- Retaining of the drug at active site.
- clearance time is longer
- High therapeutic efficacy.
- High bioavailability.
- Dose proportionality.
- Faster dissolution of active agents
- Faster dissolution generally equates with greater bioavailability.
- Lesser drug doses.
- Less toxicity.
Disadvantages of polymeric nanoparticles
- Wide use of polyvinyl alcohol as a detergent –subjects with toxicity.
- Limited targeting capabilities.
- Termination of therapy is not possible.
- Cytotoxicity. (Naik et al., 2012)
- Pulmonary inflammation and pulmonary carcinogenicity.
- The trouble of autonomic inequity by nanoparticles consumingstraightresult on heart and vascular function.
Therapeutic Applications of Nanoparticles
* Carriers of drugs and biological agents
* Carriers of gene and DNA
* Carriers of antigens & vaccines
* Controlled and targeted drug delivery
* Carriers of diagnostic agent
Polymers Used for Preparation of Polymeric Nanoparticles
The picture is having four types of polymers are can be used for the polymeric nanoparticles formulations. The natural types of polymers are the obtained from the natural sources like animal or plants. The synthetic polymers are the prepared by the chemical synthesis methods. (Senthilnathan et al., 2015)
Figure 1: Types of polymers used for polymeric nanoparticles
Preparation methods for polymeric nanoparticles
The following preparation methods are the commonly used for the polymeric nanoparticles.
Emulsion-Solvent Evaporation Method:
This methodinvolves two steps. The first step is emulsification of the polymer solution into an aqueous phase. In second step polymer solvent is evaporated, making polymer precipitation as nanospheres. The nano particles are collected by ultracentrifugation and washed with distilled water to remove additivedeposit or any free drug and lyophilized for storage.9Modification of this method is high pressure emulsification-solvent evaporation method. This method involves preparation of an emulsion which is then subjected to homogenization under high pressure followed by complete stirring to eliminate organic solvent.The size of nanoparticles is controlled by regulating the stirring rate, type and amount of dispersing agent, viscosity of organic phase and aqueous phase and temperature.
Double Emulsion and Evaporation Method:
The disadvantage of emulsion-solvent evaporation method is poor entrapment of hydrophilic drugs. The double emulsion technique is overcomes this disadvantage and encapsulate the hydrophilic drugs, which is done by the addition of aqueous drug solutions to organic polymer solution under vigorous stirring to form w/o emulsions. This w/o emulsion is added into second aqueous phase with continuous stirring to form the multiple emulsions (w/o/w emulsion). The emulsion then allowed to removal of solvent by evaporation,nanoparticles are isolated by centrifugation at high speed. The formed nanoparticles are carefully washed before lyophilisation.
Emulsions- Diffusion Method:
The polymer is dissolved in a moderately water-miscible solvent (for example propylene carbonate, benzyl alcohol), and saturated with water to ensure the initial thermo-dynamic equilibrium of both liquids.(Anusha et al., 2011) Then, the polymer-water saturated solvent phase is emulsified in aqueous solution having stabilizer, leading to solvent diffusion to the external phase and the developmentof nanoparticles, according to the oil-to-polymer ratio. Finally, the solvent is removed by evaporation or filtration, as said by its boiling point.
Salting Out Method:
In this method polymer and drug are primarilydissolved in a solvent which is afterward emulsified into an aqueous gel containing the saltingout agent (electrolytes,for example magnesium chloride and calcium chloride, or non- electrolytes as sucrose) and a colloidal stabilizer for example polyvinylpyrrolidone or hydroxyethylcellulose. This o/w emulsion is dilute with anadequate amount of water or aqueous solution to increase the dispersion of solvent into the aqueous phase, hence the formation of nanoparticles.
Solvent Displacement / Precipitation method:
Solvent displacement includes the precipitation of a preformed polymer from an organic solution and the diffusion of the organic solvent in aqueous medium in the presence or absence of the surfactant. Polymers, drug, and lipophilic surfactantsare dissolved in a semi-polar water miscible solvent for example acetone or ethanol. The solution is now poured or injected into an aqueous solution having stabilizer above magnetic stirring. Nano particles are formed immediatelyby the rapid solvent diffusion. The solvent is then removed from the suspensions under reduced pressure. This method is well suited for most of the poorly soluble drugs.
This method is created on a solvent displacement mechanism which includesextra toolsfor example dialysis tubes or semi-permeable membranes through suitable molecular weight cut-offwhich helpby way of a physical barrier for the polymer. Therefore, dialysis is achieved against anon-solvent of the polymer miscible with the polymer solvent. The movement of thepolymer solvent through the membrane induces a progressive loss of solubility of thepolymer leading to the development of homogeneous nano suspensions.
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