DRUG DELIVERY SYSTEM:

STRUCTURES, APPLICATIONS

NİL GÖLBIOTECHNOLOGY Department

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OUTLINE

1. NANOTECHNOLOGY IN DRUG DELIVERY

2. DRUG DELIVERY CARRIERS

3. STUDIES

4. CONCLUSION

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Methods of Drug Delivery

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NANOTECHNOLOGY IN DRUG DELIVERY

The key areas in which nanotechnology efforts arebeing focussed are:

1. Systems that improve the solubility and bioavailability of poorly water soluble drugs

2. Delivery vehicles that can enhance the circulatory persistence of drugs and/or target drugs to specific cells

3. Controlled release delivery systems

4. Vaccine adjuvants and delivery systems

5. Nanostructured materials that can be used in a diverse range of drug delivery applications such as orthopaedics and wound management.

İdeal” Drug Delivery System

• Inert

• Biocompatible

• Mechanically strong

• Comfortable for the patient

• Capable of achieving high drug loading

• Readily processable

• Safe from accidental release

• Simple to administer and remove

• Easy to fabricate and sterilize

• Free of leachable impurities

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Challenges to make the drug more effective via Nanotechnology:

Prevention of drug from biological degradation

Effective Targeting

Patient Compliance

Cost effectiveness

Product life extension

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Controlled Release DeliverySystems

This ability to control the release of a drug within a given timeframe offers the potential for more efficient dosing and therapeutic efficacy.

For example, in the porous silicon technology (BioSilicon), the drugs are held within the pores in the nanostructure and released as the BioSilicon nanomatrix biodegrades in the body. This technology biocompatible and safe.

Drug can also be held within a polymer reservoir and released through a nanoporous membrane over a period of up to 6 months.

Advantages of Controlled Drug Delivery

Eliminate over or underdosing

Maintain drug levels in desired range

Need for less dosing

Increased patient compliance

Prevention of side effects

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Drug delivery systems The concept of “Clever” drug targeting system includes the coordinating behavior of

three components: 1)the targeting part, 2)the carrier and 3) the therapeutic drug.

The first one recognizes and binds the target.

The second one carries the drug

The third one provides a therapeutic action to the specific site

Targeting Parts:

Antibodies

Charged molecules

Proteins

Polysaccharides

Lipoproteins

Low-molecular-weight ligands

Hormones

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Interactions Between Biological Systems and Nanostructures

The potential of targeted delivery will only be realized with a much better understanding of how such structures interact with the body and its components –in vitro and in vivo.

oInteraction of nanostructures with plasma proteins and relation between protein adsorption and removal of nanostructures from the circulation by the reticulo-endothelial system.oAdsorption of nanostructures to cells (in relation to the surface chemical characteristics, size and shape of the nanostructures).oUptake and recycling, trans-endocytosis and endosomal escape of nanostructures.oSafety evaluation: In vitro/in vivo cytotoxicity, haemocompatibility, immunogenicity and genotoxicity testing.oIn vivo carrier biodistribution and degradation.

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Nanocarriers as Drug Delivery Systems

The potential of nanocarriers as Drug Delivery Systems

Exhibit higher intracellular uptake.

Can penetrate the submucosal layers while the microcarriers are predominantly localized on the epithelial lining.

Can be administered into systemic circulation without the problems of particle aggregation or blockage of fine blood capillaries.

The development of targeted delivery is firmly built on extensive experience in pharmaco-chemistry, pharmacology, toxicology, and nowadays is being pursued as a multi-and interdisciplinary effort.

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Nanoparticles for Drug Delivery

Metal-based nanoparticles – Au, Ag, Cd-Se, Zn-S etc

Lipid-based nanoparticles – Liposome & Neosome based….

Polymer-based nanoparticles – Dendrimer, Micelle

Biological nanoparticles – Bovine-albumin serum based…

The following different types of np-based drug-delivery systems

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Polymer-based systems offer the potential for targeted cellular uptake of a therapeutic agent where the charge on the nanoparticle, influenced by its composition, leads to targeting a specific intracellular location.

Ligands can be attached to the surface of nanoparticle carriers to target a specific cell type, and targeting of drugs to the site of disease ensures enhanced efficacy at the site as well as reduced systemic toxicity.

DELİVERY VEHİCLES FOR ENHANCEDCİRCULATORY PERSİSTENCE AND

TARGETİNG

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Drug Delivery Carriers

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• Biocompatibility• Non-toxicity• Ability to entrap both

hydrophilic pharmaceuticals and hydrophobic pharmaceuticals.

• Hydrophilic pharmaceuticals are entrapped in the internal aqueous compartment of liposomes and hydrophobic pharmaceuticals are entrapped in the membrane

• Opportunity to deliver pharmaceuticals into cells or even inside individual cellular compartments.

• Modifiable structure

The popularity of liposomes as drug carriers arises from their ADVANTAGES:

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Liposomes also serve as carriers of proteins and peptides to be used in various areas.

Liposomes increase the stability of protein drugs and eliminate the troubles with protein transport across the cell membrane. Encapsulation of protein and peptide drugs into liposomes improves their therapeutic activity and reduces various side effects

Liposomal protein formulations have been used for the treatment of enzyme deficiency diseases and to modulate the immune response.

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NiosomesNon-ionic surfactant vesiclesVesicles are formed from uncharged, single chains of

lipidsSimilar to liposomesNiosomes minimizes the disadvantages associated with

liposomes, such as chemical instability, variable purity of phospholipids and high cost.

Less toxic b/c nonionicWater based, so offers high patient complianceOsmotically active & stableProvide delayed clearance from the circulation and

enhanced penetrationUsed in targeted & controlled release Surfactants are biodegradable, biocompatible & non-

İmmunogenicNo much requirement for handling & storage

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Niosomes Infrastructure consisting of

hydrophilic, amphiphilic & lipophilic moieties together.

Thus,

- used for wide range of proteins at different solubilities.

-easy penetration

But especially for amphiphilic (both hydrophilic and lipophilic) properties & lipophilic proteins

Have spherical shapes

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Polymer based nano-technology:Micelle

Micelle is an aggregate of amphiphilic molecules in water, with the nonpolar portions in the interior and the polar portions at the exterior surface, exposed to water….

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NanopowderNanopowders are powders

composed of nanoparticles, that is particles having an average diameter below 50 nanometers (nm).

Such compounds have two or more different cations (positively charged elements) in their chemical formula. An example of a complex compound is calcium titanate (CaTiO3).

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Nanopowder

Usually comprised of 3 to 5 nanoparticles together.

Nanoparticles <50 nm are powdered with to be used as drug carrier.

Nanopowders provide

-better absorption,

-enhanced dissolution rates of poorly soluble drugs.

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Nanocluster Inorganic metals are especially used for formation of

nanoclusters.

High quality nanoparticles, particle size, shape, structure, and composition are precisely controlled.

In a size range from subnanometer to ~2 nm

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NanocrystalsNanoparticles with a crystalline character (2-100nm)

No carrier material: 100% drug

Their dispersion in liquid media is called “nanosuspensions”. If the drug will be used with the liquid, it needs surfactants to stabilize.

Reduction in size leads to increased surface area and so incresead dissolution velocity.

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PRIORITY AREAS Cancer Nanotechnology

(i) Diagnosis using Quantum Dots

(ii) Tumor Targeted Delivery

(iii) Imaging

(iv) Cancer Gene Therapy

DNA Vaccines for parasitic, bacterial and viral diseases

Oral and pulmonary routes for systemic delivery of proteins and peptides

Nanotechnology in Tissue Engineering

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Targeting Ligands

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Quantum Dot Based Drug Delivery System to Target Cancer

Quantum Dots conjugated to peptide/antibodies specific against the cancer marker on the surface of the target cancer cells would be made to release the drug only when hit with laser light. This would allow control of the cells that will receive the toxin, thus minimizing side effects.

Quantum Dots:Quantum dots are tiny particles, or “nanoparticles”, of a semiconductor material, traditionally metals like cadmium or zinc (CdSe or ZnS, for example), which range from 2 to 10 nanometers in diameter (about the width of 50 atoms). 

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Although identifying novel anti-TB agents remains a priority, the development of the nanoparticle-based delivery systems for currently used agents may represent a cost-effective and promising alternative. Nanoparticles have a considerable potential for treatment of TB.

Their major advantages, such as improvement of drug bioavailability, high carrier capacity and reduction of the dosing frequency, may create a sound basis for better management of the disease, making directly observed treatment more practical and affordable.

Another important advantage of the nanoparticles is the feasibility of the versatile routes of drug administration, including oral and inhalation routes and feasibility of incorporation of both hydrophilic and hydrophobic substances. In addition, high stability of the nanoparticles suggests long shelf life.

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ConclusionThe use of Nanotechnology in medicine and more

specifically drug delivery is set to spread rapidly. For decades pharmaceutical sciences have been using nanoparticles to reduce toxicity and side effects of drugs.

However, so far, the scientific paradigm for the possible (adverse) reactivity of nanoparticles is lacking and we have little understanding of the basics of the interaction of nanoparticles with living cells, organs and organisms.

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Conclusion

A conceptual understanding of biological responses to nanomaterials is needed to develop and apply safe nanomaterials in drug delivery in the future.

Furthermore a close collaboration between those working in drug delivery and particle toxicology is necessary for the exchange of concepts, methods and know how to move this issue ahead.

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REFERENCES Aston,R., Saffie-Siebert R., Canham L., Ogden J.:Nanotechnology

Applications for Drug Delivery, pharmaceutıcal technology europe, 17(4), 21–28 (2005).

Cho,K., Wang X., Nie S.:Therapeutic Nanoparticles for Drug Delivery in Cancer, Clin Cancer Res 2008;14:1310-1316.

Jong,W.H.D., Borm,P. J.:Drug delivery and nanoparticles: Applications and hazards, Int. J. Nanomedicine 2008 June; 3(2): 133–149.

Olivier,J.,C.:Drug Transport to Brain with Targeted Nanoparticle, The American Society for Experimental NeuroTherapeutics, Inc.s, Vol. 2, 108–119, January 2005.

Suri,S.,S., Fenniri,H., Singh,B.: Nanotechnology-based drug delivery systems, Journal of Occupational Medicine and Toxicology 2007, 2:16.

Olivier,J.,C.:Drug Transport to Brain with Targeted Nanoparticle, The American Society for Experimental NeuroTherapeutics, Inc.s, Vol. 2, 108–119, January 2005.

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