Dr Manjuprasad

Moderator:Dr Princy Palatty

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OVERVIEW

Introduction

Need for novel drug delivery system

Types

Advantages

Disadvantages

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INTRODUCTION:

• Method of drug delivery can have a significant effect on its efficacy.

• Some drugs have an optimum concentration range within which maximum benefit is derived, and concentrations above or below this range can be toxic or produce no therapeutic benefit at all.

• From this, new ideas on controlling the pharmacokinetic ,pharmacodynamics , non-specific toxicity, immunogenicity, biorecognition , and efficacy of drugs were generated.

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Ideal characteristics:

• Convenient to administer

• Economical

• Should not require special skills

• Should not cause pain

• Continuous absorption of drug

• Minimal frequency of administration

• Should not be embarassing

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CONVENTIONAL DRUG DELIVERY

• Enteral

• Parenteral- injections

-inhalation

-transdermal

-transmucosal

• Local

NEED FOR NOVEL DRUG DELIVERY

To maximize therapeutic effect

To minimize adverse effects

To increase bioavailability

To minimize drug degradation

To improve compliance

To reduce the overall health cost

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CLASSIFICATION

Drug vehicles

Drug devices

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DRUG VEHICLES

MICROSPONGES:

Biologically porous inert particles, made up of

synthetic polymers with the capacity to store a

volume of an active agent upto their own weight

eg: Retin A for acne vulgaris

Carac containing flurouracil

for actinic keratosis

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IMMUNOCONJUGATES

• Monoclonal antibodies are conjugated with

drug/radioisotopes

ex: Ibritumomab tiuxetan -

they carry Cancer killing radioactive particles

directly to cancer cells of

non-hodgkins lymphoma

• Attacks cancer cells

minimizing harm to healthy tissues

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BACTERIOPHAGE

• The phages are loaded with a large payload of a

cytotoxic drug by chemical conjugation.

• the drug hygromycin conjugated to the phages by

a covalent amide bond, or the drug doxorubicin

conjugated to genetically-engineered cathepsin-B

sites on the phage coat.

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VESICULAR SYSTEM

• LIPOSOMES

Liposomes are small vesicles, formed of a bilayer of phospholipid, encapsulating an aqueous space of about 0.03 to 10 microns

The most common vehicle currently used

Non toxic, non hemolytic, non immunogenic even on repeated injection

Produced by sonication of an aqueous suspension of phospholipids

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VIROSOMES

o A virosome is a drug or vaccine delivery

mechanism consisting of unilamellar phospholipid

membrane vesicle incorporating virus derived

proteins to allow the virosomes to fuse with target

cells. Virosomes are not able to replicate.

o This strategy has been proposed for immunization

o Can be administered via mucosa, intradermal,

IM routes

o Eg: HIV1

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CHOCLEATES

o Stable particles derived from liposomes

o Composed mainly of charged phosphatidyl serine

o Chocleate delivery have shown potentiate use of

Amphotericin B

Factor V111

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• COBOSOMES

o Similar to chocleates

o But have a multilayered structure of continuous

lipid bilayer and have self assembly like cube

o They are biocompatible and show bioadhesive

property ideal for oral administration

eg: oral administration of cubosomes loaded with

insulin ( exp was done in rats)

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ETHOSOMES AND TRANSFEROSOMES

o They are like liposomes with increased flexibility

due to addition of ethanol or surfactant

o They are specifically designed for skin delivery

o Ethosomes eg: Minoxidil, acyclovir

o Transferosome eg: oestradiol, norgestrel,insulin

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eLIPOSOMES

o defined as a liposome with internal emulsion

droplets.

o The enclosed emulsion droplets in an eLiposome

add the ability to further control the location and

time of release from the liposome with ultrasound.

o Eg: Doxorubicin

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CYCLODEXTRINS

o family of compounds made up of sugar molecules

bound together in a ring

o 3 types: alpha, beta and gamma

o Beta cyclodextrin is ideal due to large cavity size

o They can act as permeation enhancer to improve

the drug absorption

o Eg: dexamethasone, nitroglycerin, nimesulide ,

iodine

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DENDRIMERS

o Highly branched synthetic

Macromolecules

Biocompatible and biodegradable

o Serve as a hub onto which

a large number of drugs can be

delivered

o Eg:5-FU

methotrexate

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Resealed Erythrocytes

Advantages

Easy isolation

Non immunogenic

Large volume of drug can be given

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Protection from premature degradation

Minimum toxic side effects

Biodegradable

Applications

Oxygen deficiency therapy

Delivery of antiviral agents

Delivery of anticancer drugs

OSMOTIC PUMPS

• small tablet shaped units consisting of drug and

osmotic substance in two different chambers

• Coated with semipermiable membrane which has

minute laser drilled holes for drug release

• Eg: iron

prazosin

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DRUG DEVICES

• Drug eluting stents

o Normal metal stents coated with a pharmacological

agent

o Agents are Sirolimus , Paclitaxel

o Sirolimus is an antiproliferative agent

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o Used in Percutaneous coronary Interventions

o Reduces chances of restenosis from 25% to 50%

• HORMONAL IUCDs

o These are 3rd generation IUCDs

o They release hormone slowly into the uterine

endometrium

o Used as contraceptives , DUB

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o Progestasert

coated with natural progesterone

Releases progesterone @65 micrograms/day

o Mirena

Coated with levonorgestrel

Releases the drug @20micrograms/day

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LASER ASSISTED TRANSDERMAL DRUG

DELIVERY

It creates aqueous micropores not deeper than the

epidermis with the help of laser scanner

Active transdermal delivery is the only way

forward to apply large molecule drugs through skin

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• Norplant

• Norplant is a form of birth control

• developed by Sheldon J. Segal

and Horatio B.

• The original Norplant consisted of a set of six

small (2.4 mm × 34 mm) silicone capsules, each

filled with 36 mg of levonorgestrel

• implanted subdermally in the upper arm and

effective for five years28

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Norplant II , consists of two small (2.5 mm

× 43 mm) silicone rods each containing

75 mg of levonorgestrel, being effective for

five years

• OCUSERT

Pilocarpine is available in an ocusert form

Used in the treatment of glaucoma

Pilocarpine is sandwiched between 2 layers of

ethylene-vinyl acetate membrane

Contains alginic acid which serves as carrier for

pilocarpine

Impregnated with titanium dioxide – makes it

easier for patient to see

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• It is placed in the cul de sac where it floats with

tears

• Tears penetrates the

microporous membrane &

releases pilocarpine

• Pilocarpine can also be

given through contact lenses

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INTRANASAL DRUG DELIVERY TO BRAIN

Drug substances can be transferred along the

olfactory nerve, bypassing BBB & entering the

brain directly

Olfactory transport is along olfactory nerve cells or

along perineural space into the CSF

Immediate drug delivery, sometimes faster than IV

route

Eg: NGF, erythropoetin and IGF

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MICROCHIPS

o They hold drug in a reservoir

o Implanted into the body under LA

o Released with the help of hand held wireless

device

o Important in chronic conditions that require careful

monitoring & precise therapy

o Compliance is improved

o Eg: PTH for osteoporosis

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PATIENT CONTROLLED ANALGESIC SYSTEM

o PCAS refers to electronically controlled, infusion

pumps

o Delivers an amount of intravenous analgesics

o Handled by the patient himself

o Narcotics are the most common analgesics

administered

o Used in cancer treatment & post operative pain

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Fentanyl given in a

lollipop formulation

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DRUG ELUTING MICRO STENTS

Microstents were coated with a polymer-drug

compound and is implanted in the angle of iris and

cornea

Diffusion controlled

release of paclitaxel or

mitomycin is used to

avoid blocking of stent

• IONTOPHORESIS

The use of an electric current to introduce the ions

of a medicament into bodily tissues

An adhesive patch containing thin electrode and

drug containing gel in contact with the skin

Depending upon the dose and energy the drug

either can act locally or

can be carried into blood

stream

Eg: pilocarpine

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USG guided transdermal drug delivery

Eg: Proteins (tPA,)

Insulin

Vaccines

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INSULIN DELIVERY

• INSULIN PENS

Lesser Injection pain

Convenient & easy to handle

More accurate dosing

Easier to use with visual & fine motor

impairments

Disadvantages

Expensive and 2 different insulin cannot be mixed

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IMPLANTABLE INSULIN PUMPS

1.Open loop

2.Closed loop:

• Also called as artificial pancreas

• Main purpose of its development was for the

management of Type1 DM

• Works on the principle of continuous glucose

monitoring of blood, changes on which feedback

will be sent to insulin pump and thus control of

blood sugar

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INSULIN INHALERS

o Inhalable insulin was available from September

2006 to October 2007 in the United States as a new

method of delivering insulin,

o but was found that injectable forms are more

efficient in controlling blood sugars than inhalable

form so was discontinued

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o On 9/13/2011 it was announced that a form of

inhalable insulin, aerosolized insulin, applied

deep into the nostrils may delay the onset

of Alzheimer's disease

o found to have betterment in memory and

mood

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ORAL INSULIN:

A chemical make-up that protects insulin during

passage through the gastrointestinal tract.

Absorption enhancers so that insulin could be

absorbed by the intestine

Rapidly acting insulin is used

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• VACCINE:

o Scientists have developed worlds first drug that

decreases destruction of islet cells

o Drug is a peptide prepared by modifying a

fragment of protein

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• RECTAL DELIVERY:

o bypass of the hepatic first pass metabolism

o The delivery is safe from presence of diet and

encounters less degrading enzymes.

• INSULIN PATCHES: designed to release

insulin slowly and continuously.

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RECENT TRENDS

OF

NANOTECHNOLOGY

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MECHANICAL DRILLING of a small tumor mass by

Nano Robots

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A MICROSCOPIC MACHINE roaming through the blood

stream and taking samples for identification and

determining concentration of different compounds

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MEDICAL NANO DEVICES could augment the

immune system by finding and disabling unwanted

bacteria and viruses

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A NANO ROBOT nibbling on a atheromatous

plaque in a blood vessel

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Clot Inducing Medical Robots are shown in

various stages of clot netting deployment

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Search for the ideal drug delivery system is

on……

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REFERENCES

Goodman & Gillman 12th edition

Target and controlled drug delivery system –novel

carrier system Y S Vyas

Controlled and novel drug delivery system -Sanjay

Jain

Verma RK., Mishra B., Garg S. Osmotically

Controlled Oral Drug

Santini, J. T., Cima M.J. & Langer, R. “A controlled

release microchip.”

Articles from wikipedia , pubmed

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THANK YOU