(PM3B) Biomacromolecules + Biologics

Question 1

What is a biologic?

Answer 1

A biomacromolecule used as a drug

Question 2

How does a biologic differ from a small molecule? What can be said for their route of delivery?

Answer 2

(1) >1000g/M - instead of <500g/M

(2) Organic (hydrophilic polypeptide) instead of a carbon chain

(3) High complexity, a single protein, moderate heterogeneity (slight mixture)

(4) Both delivered at site of action

Question 3

Give 3 examples of a biologic.

Answer 3

(1) Flu vaccine
(2) Monoclonal antibodies
(3) Insulin

Question 4

What is the most common route of administration for biologics?

Answer 4

Injection - parenterally

Question 5

What 4 categories can biologics be grouped into?

Answer 5

(1) Gene therapy - nucleic acids

(2) Polypeptides - e.g. proteins and peptides

(3) Polypeptides - e.g. monoclonal antibodies

(4) Vaccines

Question 6

What are some general pharmaceutics challenges for biologics/ biomacromolecules?

Answer 6

(1) Increased complexity

(2) Instable - inherent from biological origin

(3) Limited availability

(4) Immunogenicity - drug hypersensitivity to immune response - can lead to loss of efficacy

Question 7

Why types of complexity is there for biologics?

Answer 7

(1) Molecular complexity
(2) Functional complexity - more expensive to produce
(3) Composition complexity - manufacturing/ distribution issues

Question 8

What are biologics/ biomacromolecules unstable?

Answer 8

Formulations can go mouldy/ grow bacteria

Question 9

Are proteins stable?

Answer 9

No

Inherently unstable

Question 10

Why are proteins unstable?

Answer 10

(1) 3-4 layers of structure

(2) Polypeptide chain is susceptible to reactions with water/ oxygen

(3) Many changes are irreversible

Question 11

What are the 3-4 layers of structure of a protein?

Answer 11

(1) Primary structure
(2) Secondary structure - helices/ pleated sheets
(3) Tertiary structure - 3 dimensional structure
(4) Quaternary structure

Question 12

What is a common problem with biologic/ biomacromolecule drugs?

Answer 12

Often oral unsuitable - digested as food

Question 13

What type of biologic is insulin?

Answer 13

Polypeptide - proteins/ peptides

Question 14

How is insulin most often administered?

Answer 14

Subcutaneously

Question 15

What is the general purpose of a polypeptide biologic?

Answer 15

To emulate an endogenous protein

Question 16

What are 2 methods of pharmaceutical protein manufacture?

Answer 16

(1) Biotechnology
- Produced in microbial/ animal cell cultures
- Isolated via chromatographic + filtration steps

(2) Isolate from blood
- From blood/ tissue of animal

Question 17

What is a major downside of isolating biologics from animals’ blood/ tissue?

Answer 17

Transfer of viral infection

Question 18

What are 3 different types of insulin?

Answer 18

(1) Purified animal insulin

(2) Recombinant human insulin

(3) Variants of human insulin - changes speed of onset/ duration of action

Question 19

What is a hexema (6-mer)?

Answer 19

6 insulin molecules around a zinc ion

Question 20

What are 3 possible treatment regimes for Type 1 Diabetes?

Answer 20

(1) 1/2/3 insulin injections per day
- Short or rapid-acting

(2) Multiple daily injections (before meals)

(3) Continuous SC insulin infusion
- Programmable pump

Question 21

What are the routes of administration possible for insulin?

Answer 21

(1) IV
(2) SC

Question 22

What would be the advantages/ disadvantages of needle-free injectors?

Answer 22

(1) Fewer needles

(2) Complex to use + can cause bruising

Question 23

Why can insulin not be administered transdermally?

Answer 23

Poor bioavailability - due to high Mr and hydrophilicity

Question 24

What route of administration for insulin is most common in hospitals?

Answer 24

Intravenous injection/ infusion