Protein Drug Delivery: Learning Objectives and Key Factors

14 Questions

Which factor should be considered for protein drug delivery?

Protein molecular size

What is a potential advantage of the transdermal route of administration for protein drugs?

Low proteolytic activity

Which strategy can be used to increase protein bioavailability?

Penetration enhancers

What was insulin called in the early 1920s when it was isolated from animals?

Isletin

What is the first inhaled insulin called?

Exubera

When was the first recombinant human insulin developed?

1978

What is the main use of recombinant human erythropoietin (EPO)?

Treatment of anaemia associated with various disorders

What is the primary function of interferon beta?

Achieves beneficial effect via anti-inflammatory properties

What is the primary use of recombinant human growth hormone (hGH)?

Promotion of growth and modulation of metabolism

What is Pulmozyme used for?

Reducing viscosity in lungs of cystic fibrosis patients

What are the advantages and drawbacks of recombinant proteins?

High activity and low toxicity, short half-lives, large production amount, high cost

What do synthetic peptides like Octreotide primarily do?

Inhibit secretion of hormones and fluids, reduce gastrointestinal motility, cause vasoconstriction

What is the primary use of Polymyxins?

Topical preparation for local infections

How is Colistin occasionally used?

Treatment of urinary tract infections

Study Notes

Insulin history: pigs used for insulin production in the 1920s, protamine and zinc added for longer-acting insulins in the 1930s, first recombinant human insulin in 1978, first insulin using rDNA technology in 1982, various insulin analogues approved between 1996 and 2005.
Exubera: first inhaled insulin, developed by Sanofi-Aventis and Pfizer, marketed by Pfizer in 2006, withdrawn.
Insulin production: using micro-organisms, Oman using human insulin, no modifications, insulin analogues with modified structure.
Recombinant human erythropoietin (EPO): used to treat anaemia of chronic renal failure, used for anaemia associated with various disorders, FDA approved Darbepoetin alfa in 2003.
Interferon beta: licensed for use in relapsing remitting multiple sclerosis, believed to achieve beneficial effect via anti-inflammatory properties, improves blood-brain barrier integrity.
Recombinant human growth hormone (hGH): used for long-term replacement treatment for children with classic growth hormone deficiency, investigations focused on growth promotion and metabolism modulation.
Pulmozyme: an enzyme that cleaves DNA, reduces viscosity in lungs of cystic fibrosis patients, marketed as Pulmozyme.
Advantages and drawbacks of recombinant proteins: high activity, specific and low toxicity, short half-lives, relatively small production amount, high cost.
Synthetic peptides: somatostatin analogues, Octreotide inhibits secretion of hormones and fluids, reduces gastrointestinal motility, causes vasoconstriction, desmopressin limits water elimination in urine, bivalirudin inhibits thrombin, Pentafuside blocks HIV infection by preventing membrane fusion.
Polymyxins: used as topical preparation for local infections, bind to bacterial cell membrane and alter structure, leading to water uptake and cell death.
Colistin: occasionally used as injection/aerosol to treat Pseudomonas aeruginosa, used orally in bowel sterilization regimens, not absorbed by Neisseria spp. and Helicobacter pylori bacteria.