Pharmaceutical Biotechnology

1. Md Bellal Hossain Sajib
191-29-259
Department of Pharmacy
Daffodil International University
Proteinous drug
delivery

2. Protein
Proteins are the large organic compounds made of amino acids arranged in a linear chain and joined
together by Peptide bond.
Protein > 50 amino acids
What is proteinous drug delivery?
Protein and peptide-based drugs have great potential applications as therapeutic agents since they have
higher efficacy and lower toxicity than chemical drugs. However, difficulty with their delivery has
limited their use. In particular, their oral bioavailability is very low, and the transdermal delivery faces
absorption limitations. Therefore, most of the protein and peptide-based drugs are administered by the
parenteral route.

4. 1. Proteins offer a highly specific and complex set of functions that can’t be produced by
simple chemicals.
2. Fewer side-effects due to higher specificity.
3. The body produces many of the protein therapeutics (e.g. albumin) so they are less
likely to elicit immune response (at least theoretically).
4. If a gene is mutated or deleted, then protein therapeutics can give effective replacement
therapy of the corresponding protein.
Advantages

5. Here are some examples of proteinous drug delivery:
❑ Erythropoietin used for production of RBC.
❑ Tissue plasminogen activator is used for Heart attack, Stroke.
❑ Oxytocin maintain labor pain.
❑ Bradykinin increases the peripheral circulation.
❑ Somatostatin decrease bleeding in gastric ulcer.
❑ Gonadotropin induce ovulation.
❑ Insulin maintain blood sugar level.
Advantages

6. 1. Oral or any other extravascular preparation is extremely difficult. This is because of –
a. Digestion of the protein in digestive tract.
b. Poor and inconsistent absorption due to large size.
2. Structural changes in the protein which may lead to inactivity even toxicity.
a. Deaggregation or aggregation.
b. Change in primary structure e.g. deamination of the amino acid chains.
3. Impurities are much harder to detect and quantify due to complex structure of the proteinous drugs.
4. Phagocytosis by RES (Reticuloendothelial system) as the drug is recognized as foreign.
5. Allergic or immunogenic reactions.
Problemsencounteredduringproteinous
drugdelivery

7. We can solve the problems of proteinous drug delivery by:
1. Enzyme Inhibitor
2. Permeation enhancer
3. Chemical modification
4. Delivery System
Enzyme Inhibitor:
Resist degradation by enzymes present in stomach/intestine.
Example: Trypsin, alpha-Chymotripsin, thiol-metallopeptidase these enzymes are responsible for Insulin
degradation. To inhibit these enzymes specific Inhibitor are used such as, (1,10-Phenanthroline, P-
chloromeribenzoate, Bacitracin).
Solutions

8. Permeation enhancer:
Increases membrane permeability. There are two types of cell transporter /Pathway are involved in this process:
1. Transcellular. (Lipophilic drug will permeate by this pathway) Example: Surfactant, Bile, N-
Acetylated/Alpha-amino acid, chitosan.
2. Inter/Paracellular. (Hydrophilic drug will permeate by this pathway) Example: Chelators, Zonula
ocelodants toxin(both weaken the tight junction)
(This two transporter are the major pathways involved in the transfer of peptides and proteins across the
epithelial barriers.)
Solution

9. Chemical modification:
Improves enzymatic stability and membrane penetration.
Example: Vasopressin are used in the treatment of diabetes Incipidus.
Vasopressin converted into desmopressin. By mimicking the actions of endogenous ADH, desmopressin
acts as a selective agonist of V2 receptors expressed in the renal collecting duct (CD) to increase water
re-absorption and reduce urine production. And enhance the oral solubility and bioavailability of drug.
Solution

11. Delivery System:
1) Nano particle drug delivery system
2) Liposome drug delivery system
3) Mucoadesive drug delivery system (Most widely used)
4) Microsphere drug delivery system
❑ Nano particle drug delivery system:
Nanoparticle drug delivery systems are engineered technologies that use nanoparticles for the targeted delivery
and controlled release of therapeutic agents. Due to their small size and large surface area, drug nanoparticles
show increase solubility and thus enhanced bioavailability, additional ability to cross the blood brain barrier
(BBB)
Solution

12. ❑ Liposome drug delivery system:
Liposomes are delivery vehicles for transporting substances into the body effectively via facilitating
absorption directly in the mouth or by preventing breakdown by stomach acid.
Solution

13. • PEG is a synthetic polymer, by attaching PEG (Poly Ethylene Glycol) with liposome it will enhance the
solubility and movement of liposome.
• To aid in delivery efficiency and to allow more circulation time for cargo molecules to reach intended
diseases sites, PEG is added to shield these nanoparticles by preventing blood plasma proteins from
absorbing into the liposome surface, increasing bloodstream circulation lifetime.
• PEGylation is defined as the addition of polyethylene glycol to a biological compound to be protected from
destruction by the immune system.
• By pegylation process we can identify tumor or cancer cell very easily. Example: Toxoroposine, Paclitaxel
(for breast cancer)
WhyPEGYLATIONis importantfor liposomedrug delivery
system

14. MOA of liposome

17. Classification

18. Mucoadesive drug delivery system :
Mucoadhesive drug delivery gives rapid absorption and good bioavailability due to its considerable
surface area and high blood flow.
Achieve site-specific drug delivery.
Improves membrane permeation.
Microsphere drug delivery system
Bioadhesive microspheres are (small size and effective drug encapsulation) drug delivery systems
involve creation of intimate and prolonged contact of active ingredients with biological tissues and
prolongation of contact at target site.
Solution

19. Helmut Ringdorf first described site-specific polymeric drug delivery system for simple drugs and larger
drugs.
This model can be shown as follows–
Site-specificCarrierMoleculein TargetedDrug
Delivery

20. Ringdorf’sModelcomponent
The basic components of a polymeric drug delivery system are –
1. The polymeric backbone
2. A site-specific component also known as homing device. It will recognize the target.
3. Functional chains to control the physical and chemical properties of the carrier.
4. The drug covalently or electrostatically bonded to the polymer backbone directly or through a spacer
arm.
5. The spacer arm.

21. Ringdorf’sModelcomponent
The polymeric backbone:
The polymers used are –
1. Cationic polymers to which drug is bonded non-covalently.
• Polyethylenediamine.
• Chitosan
• Polylysine
2.Polymers for covalent conjugation with the drug
• Dextrans
• Cyclodextrins (CDs)
• HMPA/HPMA

22. Thankyou