Collagen Based Drug Delivery

Development of Collagen Based Drug Delivery Systems Ivy Kanungo Chemical Lab

Presentation Outline Background Information

Drug Delivery Systems Biomaterials Collagen Current Drug Delivery Systems Problems Associated with Collagen based Drug Delivery Aim and Objective Design Constraints Plan of Work

Drug Delivery Drug

delivery

is

the

method

or

process

of

administering a pharmaceutical compound to achieve a therapeutic effect in humans

Routes of Drug Administration





Intestinal

Rectal

Intravenous/

Nasal

Intraarterial Intramuscular/ Subcutaneous Oral Buccal / Sublingual

Pulmonary Vaginal Intrauterine Transdermal Ocular

Methods of Drug Delivery

5

Ideal Drug Delivery System Release rate dictated by the needs of the body over the period of treatment Constant, 0-order (clear PK PD) Channel the drug to the active site, cell, tissue, organ (drug targeting)

“No such DDS exists which combines ABOVE …!!!”

Improved drug delivery Continuous maintenance of drug include levels in therapeutically desirable range Potentially decreased amount of drug needed Decreased amount of dosage and possibly less invasive dosing Reduction

of

harmful

side

effects

targeted delivery to a particular site

due

to

Controlled Delivery Attempts Sustain drug action at a predetermined rate by maintaining a relatively constant, effective drug level in the body with concomitant minimization of undesirable side effects associated with a sawtooth kinetic pattern Localize drug action by spatial placement of a controlled release system (usually rate controlled) adjacent to or in the diseased tissue or organ

Target drug action by using carriers to deliver drugs to a particular “target” cell type

Targeted Drug Delivery

Drug Release Profile Concentration

Plasma drug concentrationprofiles for conventional tablet or capsule formulation, a sustained release formulation, and a zeroorder controlled release formulation

Physicochemical Properties of a Drug Influencing Design and Performance Solubility Molecular weight Chemical stability Physical stability Protein binding capability

Biological Characteristics of a Drug Influencing Design and Performance Duration of action Safety Side effects Margin of safety Role of disease state

Biomaterials BioCompatibilty Biodegradability Issues to consider: Viability Placement

Factors Influencing the Selection of the Carrier Material Size of the carrier required Inherent properties of the drugs i.e. aqueous solubility or stability Surface characteristics i.e. charge and permeability Degree of biocompatibility, biodegradability and toxicity Drug release profile required Routes of application of drugs Antigenicity of the final product

Aim Development of collagen based targeted drug delivery for sustained release

Objective Chemical modification of collagen without affecting its triple helical conformation Development of drug entrapped collagen based biomaterials for sustained release profile

Collagen: Fibrous Protein

Stabilizing Inter-strand H-bonds

Gly-Pro-HyPro Repeat

A three dimensional structure which works as a natural

distance

barrier

between

the

drug

is

incorporated into the matrix and the surroundings environment A network which enhances cell penetration and new tissue generation

Adjustable bio degradability and bio resorbability by cross linking Good resistance and tensile properties Compatible with synthetic polymers High water absorbability Partial open porosity Partial close porosity Tertiary release of the drugs

Collagen based drug delivery Sponge or Film Hydrogel mediated drug delivery Colloidal drug delivery

Limitations Sponge or film can be used for the treatment of the incision of the outer part of the body The quantity and homogeneity of drug loading into hydrogels Colloidal and

based delivery system faces dispersion

stability

problem

because

of

cohesiveness and high surface areas

their

strong

Design Constraints Better Drug entrapment Targeted delivery Inexpensive Sterile Biocompatible Sustained Delivery Profile Scaled up

Goal: Design Autonomous Medical Systems Definition:

Self-guiding,

adaptive,

Nano

multicomponent

systems on the nanoscale for diagnostic and therapeutic prevention or treatment of disease Value: changing

“smart” nanomedical systems can deal with conditions,

are

error-correcting,

and

can

provide proper dose of therapeutic response on a cellby-cell basis

Why nanoparticles are desired for drug delivery system?

?

? ? ?? ? Questions?

Concept:

Smart Targeted, Programmed Sequence

Y Y

Y Y Y Y Y Y Y Y Y Y

of Events, Nanomedicine Systems with Biomolecular Sensors for Control of Gene/Drug Delivery within Single Cell targeting and Y Y Cells Y Y entry Y Y Y Y Intracellular Y Y Y targeting Biomolecular sensing Gene/drug delivery

Y Y

Biomolecular sensors

Y Y Y Y Y

Y

Y Y

Y

Y

Y

Y Y Y

Y

Challenges: Optimal Drug Delivery to the Single Cell Changing of collagen struture and shape without affecting its amino acids sequences Use and selection of crosslinking agent Loading of drugs Potential Solution: Delivery of a drug manufacturing (in-situ) factory, not a drug

The Future …….is full of surprises and unintended consequences