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Renin Angiotensin Mechanism.

Introduction to Nanoparticles.

 

Introduction.

  • Rolland et al. (1989) created a site-specific drug delivery system using poly methacrylic nanoparticles. 

  • The primary goal of designing nanoparticles as a delivery system is to control particle size, surface characteristics, and drug discharge in order to achieve site-specific drug action. 

Advantages of Nanoparticles.

  • Any volatile pharmaceutical agent's stability is improved.

  • In terms of efficiency and effectiveness, they outperform traditional oral and intravenous administration methods. 

  • Increases the concentration of pharmaceutical agents delivered to a specific location. 

  • Polymeric nanoparticles are ideal candidates for cancer therapy, vaccine delivery, contraception, and targeted antibiotic delivery due to their polymer choice and ability to modify drug release. 

  • Polymeric nanoparticles are easily incorporated into other drug delivery-related activities, such as tissue engineering.  

Disadvantages of Nanoparticles.

  1. Particle aggregation can occur due to particle size and surface area. 

  2. Physical handling of nanoparticles in liquid and dry forms is difficult. 

  3. Limited drug loading. 

  4. Toxic metabolites may form.

Methods of Preparation:

  • Nanoparticles can be made from a wide range of materials, including polysaccharides, proteins, and synthetic polymers. 

Polymers for Nanoparticles:

  1. Natural Hydrophilic Polymers: 

    1. Proteins

      1. Gelatin

      2. Albumin

      3. Lectins

      4. Legumin 

    2. Polysaccharides

      1. Alginates

      2. Dextran

      3. Chitosan

      4. Agarose 

  2. Semisynthetic Polymers:

    1. Pseudo Latexes or artificial latexes were obtained from the dispersion of preformed polymers. 

    2. E.g. Pseudolatexes of Ethylcellulose, CAP, etc.  

    3. These are used in the preparation of Nanocapsules.

  3. Synthetic Hydrophobic Polymers: 

    1. Prepolymerized Polymers:

      1. Poly (ε-caprolactone) (PECL)

      2. Poly (Lactic acid) (PLA)

      3. Poly (lactide-co-glycolide) (PLGA)

      4. Polystyrene.

    2. Polymerized in Process Polymers:

      1. Poly (isobutyl cyanoacrylates) (PICA)

      2. Poly (butyl cyanoacrylates) (PBCA)

      3. Polyhexyl cyanoacrylates (PHCA)

      4. Poly (methacrylate) (PMMA) 

  • Selection of matrix materials depends on many factors including:

    • Size of nanoparticles required.

    • Inherent properties of the drug, e.g., stability. 

    • Surface characteristics such as charge and permeability .

    • Degree of biodegradability, biocompatibility and toxicity. 

    • Drug release profile desired.

    • Antigenicity of the final product.

  • Different techniques like polymerization, preformed polymers or ionic gelation etc are used.

  1. Preparation of nanoparticles from dispersion of preformed polymer: 

  • Dispersion of drug in preformed polymers is a common technique used to prepare biodegradable nanoparticles from poly (lactic acid) (PLA), poly (D, L-glycolide) (PLG), poly (D, L-lactide-co-glycolide) (PLGA). 

  • These can be accomplished by different methods described as below. 

    • Solvent evaporation 

    • Nano precipitation 

    • Emulsification/solvent diffusion 

    • Salting out 

    • Dialysis 

    • Supercritical fluid technology (SCF) 

  1. Preparation of nanoparticles from polymerization of monomers:

    1. Emulsion 

    2. Mini emulsion

    3. Micro emulsion 

    4. Interfacial polymerization 

    5. Controlled/Living radical polymerization.

  2. Ionic gelation or coacervation of hydrophilic polymers:

Characterization of Nanoparticles.

  1. Nanoparticle recovery and drug incorporation efficiency.

  2. Size and morphology.

  3. Specific surface.

  4. Surface charge and electrophoretic mobility.

  5. Surface hydrophobicity.

  6. Density.

  7. Molecular weight.

  8. Chemical analysis.

  9. Protein adsorption.

  10. Biodegradation.

  11. In vitro drug release. 

Application of Nanoparticulate Drug Delivery Systems:

  1. Intracellular targeting: 

    1. They target reticuloendothelial systems for intracellular infections  

    2. e.g. Ampicillin loaded poly hexyl cyanoacrylate (PIHCA) nanoparticles for salmonellosis. 

  2.  Nanoparticles in chemotherapy: 

    1. This technology is being tested for cancer treatment.

    2.  When exposed to infrared rays from a source outside the body, nanoshells become heated and cause tissue destruction. 

    3. This has been investigated using various cell lines in both in vitro and in vivo experiments. 

  3. Nanoparticles for peroral administration of Proteins and Peptides: 

    1. Proteins and peptides are increasingly being considered as therapeutic drugs due to their susceptibility to proteolytic degradation, which leads to stability; however, nanoparticle delivery aids in achieving stability. 

  4. Nanoparticles for intra-arterial applications:

    1. It functions as a carrier system for therapeutic agents such as dexamethasone and heparin to be delivered intra-arterially. 


  1. Nanoparticles for brain delivery: 

    1. The Blood-Brain Barrier is one of the barriers that drugs such as antibiotics, antineoplastic agents, and a variety of neuroleptic drugs must overcome. 

    2. e.g. Brain concentration of Doxorubicin was achieved with Nanoparticles coated with Polysorbate 80.

  2. Nanoparticles for DNA Delivery Ex-Nanosphere:

    1.  When compared to bare DNA, DNA incubated in bovine serum was more resistant to nuclease digestion.

  3. Nanoparticles for lymph targeting: 

    1. The primary goal of lymph targeting is to provide effective anticancer chemotherapy by accumulating the drug in the regional lymph node via subcutaneous administration.

  4. Nanoparticles for oligonucleotide delivery: 

    1. A new antisense oligonucleotide (ON) carrier system based on "sponge-like" alginate nanoparticles has been developed, and they are promising carriers for targeted delivery to the lungs, liver, and spleen.

  5. Adjuvant in vaccines: 

    1. Several studies on subcutaneous or oral administration have shown that nanoparticles have an adjuvant effect with either matrix entrapped or surface adsorbed vaccine. 

    2. Polymethyl-methacrylate nanoparticles, for example, were used as adjuvants in the HIV-2 whole virus vaccine.

  6. Nanoparticles for transdermal application:

    1.  Improves absorption and permeation. 

  7. Nanoparticles for enzyme immunoassays with adsorbed enzymes. 

  8. Nanoparticles for radioactive or contrast agents for Radio-Imaging. 

  9. Nanoparticles as functionalized nanoparticles for enzyme immobilization, controlled release polymeric systems, etc.

  10. Nanoparticles provide a larger surface area, better absorption and hence useful for diabetic wound healing.


Commonly Asked Questions:

  1. Write a detailed account of Nanoparticles as a drug delivery system.

  2. Give applications of nanoparticles as targeted drug delivery system.
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