NANOMEDICINE & DRUG DELIVERY

SYSTEMS
UNIT 1-PROSPECT OF NANOMEDICINE

BIO-PHARMACEUTICALS

Seminar by
R.DELMA JONES RUFINA
II M.Tech-NST
 PREAMBLE
ü Biopharmaceuticals are medical drugs produced using
biotechnology
ü They are proteins (including antibodies), nucleic acids used for
therapeutic or in vivo diagnostic
ü produced by other than direct extraction from biological source

a pharmaceutical product manufactured by biotechnology

methods (involving live organisms;bioprocessing);
First Substance Approved For Therapeutic Use:
ü biosynthetic 'human' insulin (humulin) made via recombinant DNA
technology
ü
ü
 CLASSIFICATION
According to biological roles of proteins
ü Enzymes – Catalyses virtually all chemical reactions i.e. 6GDH
ü Transport proteins i.e. Haemoglobin of erythrocytes
ü Contractile or Motile proteins i.e. Actin and Myosin
ü Structural proteins i.e.Collagen
ü Defense proteins i.e. Immunoglobulinsand Antibodies
ü Regulatory proteins i.e. insulin
ü Nutrient and storage proteins i.e. Ovalbumin
SOME EXPLANATIONS………………
ü
üThrombolytic agents (tissue plasminogen activator)
plasminogen plasmin
protein involved in blood clot removal
ü
üHormones (insulin, glucagon, growth hormone, gonadotrophins)

üCS Factor
glycoprotein harmone binds to hemopoietic stem cells
üHaematopoietic growth factors (Erythropoietin)
gylcoprotein harmone controls erythropoiesis

üInterferons (Interferons-α, -β, -γ)

proteins relesed by lymphocytes

üMonoclonal antibodies (Various)

 BIOPHARMACEUTICALS PRODUCTION
ü
Biotechnology makes large-scale production of existing substances using
ü microbial cells
ü mammalian cell lines,tissues
ü plant cell cultures, whole cultivation
ü
Mechanism behind is
ü Transgenic
ü DNA recombinant technology
MECHANISM
 PLANT BIOPHARMACEUTICALS
Strengths:
üAccess new manufacturing facilities
üHigh production rates/high protein yield
üRelatively fast 'gene to protein' time
üSafety benefits;no human pathogens
üStable cell lines/high genetic stability
üSimple medium (water, minerals & light)
üEasy purification

Weaknesses:
üNo approved products yet (but Phase III)
üNo final guidelines yet (but drafts available)

Threats:
üFood chain contamination
üSegregation risk
SOURCE
PRODUCTS
 CHALLENGES IN PROTEINS
üVery large and unstable molecules held by weak non-covalent forces
üEasily destroyed by relatively mild storage conditions
üHard to obtain in large quantities

Elimination by B and T cells

Proteolysis by endo/exo peptidases
Small proteins (< 30 kD) filtered out by the kidneys very quickly
Unwanted allergic reactions may develop (even toxicity)
Loss due to insolubility/adsorption

Noncovalent Covalent
Denaturation - Deamidation
Aggregation - Oxidation
Precipitation - Disulfide exchange
Adsorption - Proteolysis
Storage Formulatio
n

Delivery

11
 STORAGE MECHANISM
üRefrigeration
üFreeze-Drying
üAdditives
•Addition of stabilizing salts or ions (Zn+ for insulin)
•Addition of polyols (glycerol and/or polyethylene glycol) to
solubilize
•Addition of sugars or dextran to displace water or reduce
microbe growth
•Use of surfactants (CHAPS) to reduce adsorption and
aggregation
 PROTEIN FORMULATION
ü
Protein sequence modification
(site directed mutagenisis)

PEGylation

Proteinylation

Peptide Micelles

Formulating with permeabilizers

1.Site Directed Mutagenesis:
üAllows amino acid substitutions at specific sites in a protein

üi.e. substituting a Met to a Leu will reduce likelihood of oxidation

üStrategic placement of cysteines to produce disulfides to increase Tm

üProtein engineering (size, shape, etc.)

E343H
2.PEGylation

üPEG is a non-toxic, hydrophilic, FDA approved, uncharged polymer

üIncreases in vivo half life
üDecreases immunogenicity
üIncreases protease resistance, solubility & stability
OH OH OH OH OH OH OH OH OH OH
| |
CH-CH-CH-CH-CH-CH-CH-CH-CH-CH
| | | | |

+
| | |
cont……

Peptide-PEG monomers

Hydrophobic block Hydrophobic block

Peptide Peptide

O H R2 H O H O H R2 H O H
R4 R4
H3N+ N O H3N+ N O
N N N N
H H H H H H
R1 O H R3 R1 O H R3
O O
3.Proteinylation
üAttachment of additional or secondary (nonimmunogenic) proteins for
in vivo protection
üIncreases in vivo half life (10X)
üCross-linking with Serum Albumin
üCross-linking or connecting by protein engineering with antibody
fragments

Protein Drug ScFv (antibody)

4.Formulation with permeabilizers
üSalicylates (aspirin)
üFatty acids
üMetal chelators (EDTA)
üAnything that is known to “punch holes” into the intestine or
lumen
 DELIVERY
ü
ü Polymeric drug delivery
ü Microencapsulation
ü Liposomal delivery
ü Niosomal delivery
•

MECHANISM
•

ü Proteins in pumps
ü Oral protein delivery
ü Nasal delivery
ü Pulmonary delivery
ü Ocular delivery
ü Patch delivery
•
 LEVELS OF TESTING
Biochemical Testing
DRUG + receptor + transduction
BINDING system (second
messenger;
enzyme)
Isolated Tissue Experiments
Functional whole or part organs
Whole Animal Experiments

Anaesthetised Or Conscious Animals

ü{Phase 0 (non-clinical)}
üPhase 1 (volunteers)
üPhase 2 (patients)
üPhase 3 (large scale multi-centre)
üPhase 4 (post registration monitoring)
 NANO BIOPHARMACEUTICALS
Nanoparticles including various nanodimensional entities such as
ü
ü molecular imprinted polymers
ü metallofullerenes
ü prodrug delivery
ü oral, injectable and implantable, pulmonary, and transdermal and
transmucosal delivery have come up.
THANK YOU...