20/03/2008 Dept. of Pharmaceutics 1 Nanotechnology Based Drug Delivery Dr. Basavaraj K. Nanjwade M.Pharm., Ph.D Associate Professor Department of Pharmaceutics

20/03/200820/03/2008 Dept. of PharmaceuticsDept. of Pharmaceutics 11

Nanotechnology Based Drug DeliveryNanotechnology Based Drug Delivery

Dr. Basavaraj K. Nanjwade Dr. Basavaraj K. Nanjwade M.Pharm., Ph.DM.Pharm., Ph.D

Associate ProfessorAssociate ProfessorDepartment of PharmaceuticsDepartment of Pharmaceutics

JN Medical CollegeJN Medical CollegeKLE UniversityKLE University

Belgaum-590010Belgaum-590010


Applications of NanotechnologyApplications of Nanotechnology


Targeted Drug DeliveryTargeted Drug Delivery


Nanoparticles for Drug DeliveryNanoparticles for Drug Delivery

Metal-based nanoparticlesMetal-based nanoparticles

Lipid-based nanoparticlesLipid-based nanoparticles

Polymer-based nanoparticlesPolymer-based nanoparticles

Biological nanoparticlesBiological nanoparticles


NanobiopharmaceuticalsNanobiopharmaceuticalsIn biopharmaceuticals, in addition to the In biopharmaceuticals, in addition to the main technologies covered-liposomal, main technologies covered-liposomal, monoclonal antibody-based, and polymer-monoclonal antibody-based, and polymer-based technologies host of newer based technologies host of newer technologies such as nanoparticles technologies such as nanoparticles including various nanodimensional entities including various nanodimensional entities such as molecular imprinted polymers, such as molecular imprinted polymers, metallofullerenes, prodrug delivery, oral, metallofullerenes, prodrug delivery, oral, injectable and implantable, pulmonary, and injectable and implantable, pulmonary, and transdermal and transmucosal delivery transdermal and transmucosal delivery have come up. have come up.


Drug Delivery Technology Important to Drug Delivery Technology Important to Pharma IndustryPharma Industry

Drug delivery formulations involve low cost Drug delivery formulations involve low cost research compared that for discovery of research compared that for discovery of new molecule, new molecule,

Minimizing the drug use would significantly Minimizing the drug use would significantly reduce the effective cost of drug which reduce the effective cost of drug which would give financial relief to the patients, would give financial relief to the patients,


Delivery systems increase commercial Delivery systems increase commercial opportunity by distinguishing a drug from opportunity by distinguishing a drug from competitive threats posed by “me too” competitive threats posed by “me too” drugs and drugs and

Novel means of delivery particularly using Novel means of delivery particularly using nano-carriers, can allow branded drugs to nano-carriers, can allow branded drugs to be rescued from abyss of generic be rescued from abyss of generic competition (may be called “resurrection of competition (may be called “resurrection of drug”). drug”).

Drug Delivery Technology Important to Drug Delivery Technology Important to Pharma IndustryPharma Industry


SOME SIGNIFICANT ACHIEVEMENTS OF SOME SIGNIFICANT ACHIEVEMENTS OF NANODEVICES NANODEVICES

Development of one dose a day ciprofloxacin using Development of one dose a day ciprofloxacin using nanotechnologynanotechnology

Tumor targeted taxol delivery using nanoparticles in Tumor targeted taxol delivery using nanoparticles in Phase 2 clinical trial stagePhase 2 clinical trial stage

Improved ophthalmic delivery formulation using Improved ophthalmic delivery formulation using smart hydrogel nanoparticlessmart hydrogel nanoparticles

Oral insulin formulation using nanoparticles carriers.Oral insulin formulation using nanoparticles carriers.

Liposomal based Amphotericin B formulationLiposomal based Amphotericin B formulation


CHALLENGESCHALLENGES

Prevention of drug from biological degradationPrevention of drug from biological degradation

Effective TargetingEffective Targeting

Patient CompliancePatient Compliance

Cost effectivenessCost effectiveness

Product life extensionProduct life extension


PRIORITY AREASPRIORITY AREASCancer NanotechnologyCancer Nanotechnology

(i) (i) Diagnosis using Quantum Diagnosis using Quantum

DotsDots

(ii) Tumor Targeted Delivery(ii) Tumor Targeted Delivery

(iii) (iii) ImagingImaging

(iv) Cancer Gene Therapy(iv) Cancer Gene Therapy


PRIORITY AREASPRIORITY AREAS

DNA Vaccines for parasitic, bacterial and DNA Vaccines for parasitic, bacterial and viral diseasesviral diseases

Oral and pulmonary routes for systemic Oral and pulmonary routes for systemic delivery of proteins and peptidesdelivery of proteins and peptides

Nanotechnology in Tissue EngineeringNanotechnology in Tissue Engineering


Drug Delivery CarriersDrug Delivery Carriers


Targeting LigandsTargeting Ligands


Liposome's Liposome's


Liposome'sLiposome's

Their exterior lipid bilayer is very chemically reactive, thereby providing a Their exterior lipid bilayer is very chemically reactive, thereby providing a means to conveniently couple “tags” on a covalent basis. means to conveniently couple “tags” on a covalent basis.

Such “tags” can be antibodies, antigens, cell receptors, nucleic acid Such “tags” can be antibodies, antigens, cell receptors, nucleic acid probes, etc. probes, etc.

This provides significant versatility in assay formats (i.e., immunoassay, This provides significant versatility in assay formats (i.e., immunoassay, receptor-based, nucleic acid probe, etc.) possible. receptor-based, nucleic acid probe, etc.) possible.

With diameters ranging in size from approximately 50 nm to 800 nm, their With diameters ranging in size from approximately 50 nm to 800 nm, their aqueous core encapsulates up to millions of molecules of signal generating aqueous core encapsulates up to millions of molecules of signal generating “markers” that can be detected in a variety of different way. “markers” that can be detected in a variety of different way.

A variety of different encapsulants are possible including visually A variety of different encapsulants are possible including visually detectable dyes (since the lipid bilayer is transparent), optically and detectable dyes (since the lipid bilayer is transparent), optically and fluorometrically detectable dyes, enzymes, and electroactive compounds. fluorometrically detectable dyes, enzymes, and electroactive compounds.

This provides significant versatility in the detection schemes possible.This provides significant versatility in the detection schemes possible.


NiosomesNiosomes


NiosomesNiosomesNiosomes, non-ionic surfactant vesicles, are widely studied as an Niosomes, non-ionic surfactant vesicles, are widely studied as an alternative to liposomesalternative to liposomes

These vesicles appear to be similar to liposomes in terms of their These vesicles appear to be similar to liposomes in terms of their physical propertiesphysical properties

They are also prepared in the same way and under a variety of They are also prepared in the same way and under a variety of conditions, from unilamellar or multilamellar structures.conditions, from unilamellar or multilamellar structures.

Niosomes alleviate the disadvantages associated with liposomes, Niosomes alleviate the disadvantages associated with liposomes, such as chemical instability, variable purity of phospholipids and such as chemical instability, variable purity of phospholipids and high cost.high cost.

They have the potential for controlled and targated drug deliveryThey have the potential for controlled and targated drug delivery

Niosomes enhanced the penetration of drugsNiosomes enhanced the penetration of drugs


NanopowderNanopowder


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

A jar of a true nanopowder when emptied from A jar of a true nanopowder when emptied from chest height to toward the floor will disperse into chest height to toward the floor will disperse into the air before reaching the floor. the air before reaching the floor.

Most manufacturers of “nanopowders” produce Most manufacturers of “nanopowders” produce micropowder assemblies of nanoparticles but the micropowder assemblies of nanoparticles but the powder itself is rarely a nanopowder. powder itself is rarely a nanopowder.

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


NanoclusterNanocluster


NanoclusterNanoclusterOne of the central themes in nanoscience One of the central themes in nanoscience research is to synthesize high quality research is to synthesize high quality nanoparticles with precise control over nanoparticles with precise control over particle size, shape, structure, and particle size, shape, structure, and composition. composition.

For inorganic nanoparticles (e.g. metal and For inorganic nanoparticles (e.g. metal and semiconductor), two regimes are of semiconductor), two regimes are of particular interest, that is, nanoclusters in particular interest, that is, nanoclusters in a size range from subnanometer to ~2 nm a size range from subnanometer to ~2 nm and nanocrystals (typically 2-100 nm).and nanocrystals (typically 2-100 nm).


NanocrystalsNanocrystals


NanocrystalsNanocrystals

When the size of the material is reduced to less than 100 When the size of the material is reduced to less than 100 nanometers, the realm of quantum physics takes over and nanometers, the realm of quantum physics takes over and materials begin to demonstrate entirely new properties. materials begin to demonstrate entirely new properties.

Nano-design of drugs by various techniques like milling, Nano-design of drugs by various techniques like milling, high pressure homogenization, controlled precipitation etc., high pressure homogenization, controlled precipitation etc., are explored to produce, drug nanocrystals, nanoparticles, are explored to produce, drug nanocrystals, nanoparticles, nanoprecipitates, nanosuspensions (which for ease of nanoprecipitates, nanosuspensions (which for ease of understanding commonly mentioned as nanocrystals). understanding commonly mentioned as nanocrystals).

As decreased size will increase the solubility of drugs As decreased size will increase the solubility of drugs hence, this technology is explored to increase oral hence, this technology is explored to increase oral bioavailability of sparingly water soluble drugs.bioavailability of sparingly water soluble drugs.


MicelleMicelle


MicelleMicelle

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

Amphiphilic molecules form micelle above a particular concentration which is Amphiphilic molecules form micelle above a particular concentration which is called as critical micellar concentration (CMC). called as critical micellar concentration (CMC).

Micelles are known to have an anisotropic water distribution within their Micelles are known to have an anisotropic water distribution within their structure, means water concentration decreases from the surface towards structure, means water concentration decreases from the surface towards the core of the micelle, with a completely hydrophobic (water-excluded) core. the core of the micelle, with a completely hydrophobic (water-excluded) core.

Hydrophobic drugs can be encapsulated/solubalized, into inner core. Hydrophobic drugs can be encapsulated/solubalized, into inner core.

The spatial position of a solubilized drug in a micelle will depend on its The spatial position of a solubilized drug in a micelle will depend on its polarity, nonpolar molecules will be solubilized in the micellar core, and polarity, nonpolar molecules will be solubilized in the micellar core, and substances with intermediate polarity will be distributed along the surfactant substances with intermediate polarity will be distributed along the surfactant molecules in certain intermediate molecules in certain intermediate positions. positions.


Dendrimers Dendrimers


DendrimersDendrimers

These branched macromolecules are constructed around a These branched macromolecules are constructed around a simple core unit. simple core unit.

Dendrimers have a high degree of molecular uniformity, Dendrimers have a high degree of molecular uniformity, narrow molecular weight distribution, specific size and narrow molecular weight distribution, specific size and shape characteristics, and a highly- functionalized shape characteristics, and a highly- functionalized terminal surface. terminal surface.

The manufacturing process is a series of repetitive steps The manufacturing process is a series of repetitive steps starting with a central initiator core. Each subsequent starting with a central initiator core. Each subsequent growth step represents a new "generation" of polymer with growth step represents a new "generation" of polymer with a larger molecular diameter, twice the number of reactive a larger molecular diameter, twice the number of reactive surface sites, and approximately double the molecular surface sites, and approximately double the molecular weight of the preceding generation.weight of the preceding generation.


Polymeric Nanoparticles Polymeric Nanoparticles


Polymeric NanoparticlesPolymeric Nanoparticles

In recent years, biodegradable polymeric In recent years, biodegradable polymeric nanoparticles have attracted considerable nanoparticles have attracted considerable attention as potential drug delivery attention as potential drug delivery devices in view of their applications in devices in view of their applications in drug targeting to particular organs/tissues, drug targeting to particular organs/tissues, as carriers of DNA as carriers of DNA in gene therapy, and in their ability to in gene therapy, and in their ability to deliver proteins, peptides and genes deliver proteins, peptides and genes through a per oral route of administration. through a per oral route of administration.


Carbon 60Carbon 60


Carbon 60 Carbon 60

C60 are spherical molecules about 1nm in C60 are spherical molecules about 1nm in diameter, comprising 60 carbon atoms diameter, comprising 60 carbon atoms arranged as 20 hexagons and 12 pentagons: the arranged as 20 hexagons and 12 pentagons: the configuration of a football. configuration of a football.

Hence they find application as Hence they find application as NanoPharmaceuticals with large drug payload in NanoPharmaceuticals with large drug payload in their cage like structure. their cage like structure.

On the other hand with development of various On the other hand with development of various chemical substitutes for C60, it is possible to chemical substitutes for C60, it is possible to develop functionalized C60 with better drug develop functionalized C60 with better drug targeting properties targeting properties


Carbon NanotubeCarbon Nanotube


Carbon NanotubeCarbon Nanotube

Carbon nanotubes are adept at entering the Carbon nanotubes are adept at entering the nuclei of cells and may one day be used to nuclei of cells and may one day be used to deliver drugs and vaccines. deliver drugs and vaccines.

The modified nanotubes have so far only been The modified nanotubes have so far only been used to ferry a small peptide into the nuclei of used to ferry a small peptide into the nuclei of fibroblast cells. fibroblast cells.

But the researchers are hopeful that the But the researchers are hopeful that the technique may one day form the basis for new technique may one day form the basis for new anti-cancer treatments, gene therapies and anti-cancer treatments, gene therapies and vaccines.vaccines.


Equipments for NanoparticlesEquipments for Nanoparticles

1.Homogenizer

2.Ultra Sonicator

3.Mills

4.Spray Milling

5.Supercritical Fluid Technology

6.Electrospray

7.Ultracentrifugation

8.Nanofiltration


Homogenizer & Ultra SonicatorHomogenizer & Ultra Sonicator


Methods of Drug DeliveryMethods of Drug Delivery


E-mail: [email protected]: [email protected]

Documents

20/03/2008 Dept. of Pharmaceutics 1 Nanotechnology Based Drug Delivery Dr. Basavaraj K. Nanjwade M.Pharm., Ph.D Associate Professor Department of Pharmaceutics