Protein Drug Delivery: Learning Objectives and Key Factors

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Exubera: first inhaled insulin, developed by Sanofi-Aventis and Pfizer, marketed by Pfizer in 2006, withdrawn.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.