Magnetic nanoparticles as carriers in drug delivery – Challenges & future opportunities Venkat Manohar Indian Institute of Chromatography & Mass Spectrometry(IICMS) Chennai -32

Drug discovery ‘game’ Drug discovery  game  !! !!

> 1000 000

Assessment of target  Expression Target localization Quantification 

Lead Optimization Efficacy

Pre‐clinical  studies Dosing PK/TK safety

Clinical phases I‐III Clinical phases I III Safety Dosage Efficacy PK Metabolites

5 to 6 

3.8 Years

Jurgen k. Willmann,et.al., Nature Rev., 7, 2008, 591

FDA  approval

1

8.6 years

1.8 Years

Launch

W shall We h ll discuss di z Basic requirements of drug delivery z Nanoparticles p in drug g delivery y z Magnetism & biology z Magnetic nanoparticle and its role z An example z In I future…. f t

*Drug synthesis & drug product ÐDrug substance- API ÐDrug product - bridge chemistry with biology ÐDrug product d - numerous aspects of f formulation -Solubility -Delivery y -Efficacy No toxicity -No *Hovig Kouyoumdjian, Michigan State University, 2009

Ideal drug delivery process

Formulation Absorption Distribution

Metabolism

*Hovig Kouyoumdjian, Michigan State University, 2009

Ideal Mail delivery process

*Hovig Kouyoumdjian, Michigan State University, 2009

Id l M il d li Ideal Mail delivery process

Receiving 

Processing

Delivering

*Hovig Kouyoumdjian, Michigan State University, 2009

Id l M il d li Ideal Mail delivery process

*Hovig Kouyoumdjian, Michigan State University, 2009

Aspects of Drug Delivery z The The ability to specifically formulate drugs to achieve   ability to specifically formulate drugs to achieve better absorption, distribution, metabolism and  excretion (ADME) properties z Drugs can be delivered as free molecules or  bound to carriers z Pharmacologically active compounds usually delivered  combined to a carrier combined to a carrier

Silverman, R. B. The Organic Chemistry of Drug Design and Drug Action; 2nd ed.; Elsevier Academic Press, 2004, 10

O l D li Oral Delivery Ñ Ñ Ñ

Oral delivery involves  transport of drug via  fd i gastrointestinal tract Drugs are readily  metabolized in liver

*Hovig Kouyoumdjian, Michigan State University, 2009

Intravenous u Delivery D y Bioavailability a  Bioavailability a problem with  intravenous delivery intravenous delivery §Instability §Toxicity

Ò

Enhanced Bioavailability Ð Bioavailability is obtained Bioavailability is obtained when drug is resistant to liver metabolism Ð Two conditions should be met for better delivery Ð Site specificity Ð Prolonged release

An  ideal drug delivery vehicle ………. Should also possess a trigger allowing for the rapid and complete release of free drug within ithi th the ti tissue Should achieve high g intravascular drug g concentrations necessary for driving cellular drug uptake Should increase drug penetration further from vessels Chelsea D. Landon, et.al., The Open Nanomedicine Journal, 2011, 3, 38‐64

Wonderful happenings in physics…

Kamerlingh li h Onnes

Low temperature …. goes  down and down…

Percy Bridgman  

High pressure /vacuum …  goes higher and higher….

Feynmann

Controlling “things” on a  small scale ….  smaller and  smaller…. ll

Nanotechnology & drug delivery Famous lecture of  Dr Feynmann on  December 29, 1959 on title,  called  “There’s plenty of room at the  bottom”, American Physical Society,  Caltech., USA. Caltech., USA. In ancient Greek, “Nano”  means “dwarf”  The vision for nanotechnology laid as early as 1959..!! Nanotechnology – N t h l creation and utilization of materials at  ti d tili ti f t i l t nanometer length scale P ti l Particles