L1: Pharmaceutical biotechnology & biologics

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What is Small Molecule and Large Molecule in drug delivery.

🔹Q: What are SMALL MOLECULES in drug delivery?

Drugs synthesized by classical chemical rxns between organic and/or inorganic compounds.

• They typically have:

  • ⬇Low MW

  • Simple, well-defined structures

  • ✅Good stability @ room temp

  • 💊Oral ROA capability

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What is Small Molecule and Large Molecule in drug delivery.

🔹Q: What is one example of Small molecule?

Aspirin (MW ≈ 180 Da)

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What is Small Molecule and Large Molecule in drug delivery.

🔹Q: What are LARGE MOLECULES (Biologics) in drug delivery?

Large molecules = Biologics/Macromolecules

• These are drugs based on:

  • Proteins

  • Peptides

  • mAbs (Monoclonal Ab)

  • Vaccines

  • Hormones

  • Ab

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What is Small Molecule and Large Molecule in drug delivery.

🔹Q: How are Large Molecules produced?

They are produced using Living Cells or Biotechnology and may reach MW up to 150,000 Da (150 kDa).

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What is Small Molecule and Large Molecule in drug delivery.

🔹Q: What is one example of Large Molecule?

Insulin (Human insulin)

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What is Small Molecule and Large Molecule in drug delivery.

🔹Q: What are the major difference between SMALL vs. LARGE molecules?

Small Molecules	Large Molecules (Biologics)
⬇Low molecular weight	⬆High molecular weight
STABLE at room temperature	UNSTABLE at room temperature
Usually oral (PO)	Usually parenteral
Chemically synthesized	Produced from living cells/biotechnology
⬇Rare immunogenicity	⬆Higher risk of immunogenicity

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What is Small Molecule and Large Molecule in drug delivery.

🔹Q: Why are most biologics not given orally?

Most biotech drug products CANNOT be administered Orally b/c they are UNSTABLE in the acidic environment of the stomach.

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What is Small Molecule and Large Molecule in drug delivery.

🔹Q: What are common Delivery Routes for BIOTECH drug products?

• Nasal

• Inhalation

• Buccal/Sublingual

• Parenteral

• Transdermal

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What is Small Molecule and Large Molecule in drug delivery.

🔹Q: What is Biotechnology in pharmaceuticals?

Biotech involves using LIVING ORGANISMS, CELLS, or GENETIC ENGINEERING techniques to produce beneficial pharmaceutical products such as:

• Recombinant proteins

• Vaccines

• Hormones

• mAbs (monoclonal Ab)

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What is Small Molecule and Large Molecule in drug delivery.

🔹Q: What is an IMPORTANT exam point abt BIOLOGICS vs. SMALL Molecules?

➡SMALL molecules = chemically synthesized

➡LARGE molecules / BIOLOGICS = produced from LIVING systems through Biotech

👉BIOLOGICS = larger, ⬇less stable, & ⬆More immunogenic THAN Small molecules.

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Differentiate between small Vs large molecule therapeutics.

🔹Q: What is the main difference between small molecule and large molecule therapeutics?

Small Molecules	Large Molecules
Chemically synthesized	Produces by biotechnology
⬇Low MW	⬆High MW
STABLE	UNSTABLE
Usually ORAL	Usually PARENTERAL
⬇Rare immunogenicity	⬆Higher immunogenicity

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Differentiate between small Vs large molecule therapeutics.

🔹Q: Which has a ⬇LOW MW? Which has a ⬆HIGH MW?

• ⬇Low MW = Small molecules

• ⬆High MW = Large molecules / Biologics

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Differentiate between small Vs large molecule therapeutics.

🔹Q: Which is STABLE @ room temp? Which is UNSTABLE @ room temp?

• ✅STABLE = SMALL molcules

• ❌UNSTABLE = LARGE molecules / BIOLOGICS → 🥶Refrigerate/cold storage

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Differentiate between small Vs large molecule therapeutics.

🔹Q: Which has PO administration? Which has PARENTERAL administration?

• 💊PO = SMALL molecules

• 💉PARENTERAL = LARGE molecules / BIOLOGICS → b/c they’re unstable in the stomach’s acidic environment

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Differentiate between small Vs large molecule therapeutics.

🔹Q: How are SMALL Molecules produced?

They’re synthesized through Chemical rxns between organic and/or inorganic compounds.

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Differentiate between small Vs large molecule therapeutics.

🔹Q: How are LARGE Molecules / BIOLOGICS produced?

They’re made from LIVING CELLS/ORGANISMS using biotech & recombinant DNA tech.

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Differentiate between small Vs large molecule therapeutics.

🔹Q: Which has Rare Immunogenicity? Which has Higher risk of Immunogenicity?

• ⬇Rare immunogenicity = SMALL molecules

• ⬆Higher risk of immunogenicity = LARGE molecules / BIOLOGICS

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Differentiate between small Vs large molecule therapeutics.

🔹Q: Examples of SMALL molecules?

• Aspirin (MW ≈ 180 Da)

• Metformin

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Differentiate between small Vs large molecule therapeutics.

🔹Q: Examples of LARGE molecules?

• Insulin

• mAbs (monoclonal Abs)

• EPO (erythropoietin)

• Human Growth HORMONE (HGH)

• Vaccines

• Exenatide (Byetta) → mimics GLP-1 (for T2DM)

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Discuss pharmaceutical application of biotechnology.

🔹Q: What is pharmaceutical BIOTECH?

Involves using LIVING organism, cells, genetic engineering, or molecular components to produce beneficial pharmaceutical products.

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Discuss pharmaceutical application of biotechnology.

🔹Q: What are some applications of BIOTECH in pharmaceuticals?

• Recombinant proteins

• Modified proteins

• Vaccines

• Genetic engineering

• Biologics: hormones, Ab, peptides

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Enlist the routes of delivery of biotechnological products.

🔹Q: Why are many biotechnology drug products not given orally?

Most BIOTECH drug products CANNOT be administered Orally b/c they are UNSTABLE in the strong acidic environment of the stomach.

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Enlist the routes of delivery of biotechnological products.

🔹What are the major ROUTES of Delivery for Biotechnology drug products?

• Nasal

• Inhalation

• Buccal/Sublingual

• Parenteral - IV, IM, SC

• Transdermal

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Types of biotechnology-derived products/Biologics.

1. Peptides and Proteins - Erythropoietin, Tissue plasminogen activator.

🔹Q: What is Erythropoietin (EPO)?

Glycoprotein that stimulates the production of RBC (erythrocytes) in the Bone marrow.

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🔹Q: What is the source of Erythropoietin (EPO)?

Glycoprotein naturally produced by the Peritubular cells of the KIDNEYS in response to Hypoxia.

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🔹Q: What condition is Erythropoietin (EPO) used to treat?

Anemia

• Kidney Dialysis patients

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🔹Q: Where is Erythropoietin (EPO) naturally produced?

Naturally produced by the KIDNEYS (Peritubular cells) in response to HYPOXIA (⬇Low oxygen).

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🔹Q: What does tissue plasminogen activator (tPA) do?

tPA ⬇breaks down Blood Clots (thrombi) & 🔨restores blood flow.

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🔹Q: What is the source of tissue plasminogen activator (tPA)?

Natural human PROTEASE that binds Fibrin & breaks down Blood Clots.

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🔹Q: Why is tPA called a “clot buster”?

B/c it DISSOLVES BLOOD CLOTS, esp. during acute stroke or MI (myocardial infarction).

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Types of biotechnology-derived products/Biologics.

2. Hormones – Leuprolide, exenatide (Byetta).

🔹Q: What does Leuprolide do in men and women?

• ⬇Testosterone in 🧔‍♂MEN

• ⬇Estrogen in 👱‍♀WOMEN

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🔹Q: What is the source of Leuprolide?

• Man-made protein / synthetic hormone that acts like a natural hormone in the body.

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🔹Q: What conditions is Leuprolide used to treat?

• Prostate cancer

• Endometriosis

• Uterine fibrosis

• Other FEMALE Hormone-related conditions

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🔹Q: What does Exenatide (Byetta) MIMIC?

GLP-1

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🔹Q: What condition is Exenatide (Byetta) used to treat?

• T2DM

• Glycemic control

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🔹Q: What is the source of Exenatide (Byetta)?

Synthetic version of extending-4, a hormone found in the SALIVA of the 🦎VENOMOUS LIZARD GILA MONSTER.

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Types of biotechnology-derived products/Biologics.

3. Vaccines.

🔹Q: What is the source of vaccines?

Vaccines are biological preparations made from:

• Attenuated (weakened) pathogens

• Inactivated pathogens

• Toxins

• Surface proteins

• Antigens (pieces of microorganisms)

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🔹Q: What disease conditions are Vaccines used for?

Vaccines provide ACTIVE ACQUIRED IMMUNITY against infectious disease such as:

• MMR (Measles, Mumps, Rubella)

• Hep. A & B

• Rabies

• Polio

• Typhoid

• Cholera

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🔹Q: What the source (and disease) of Attenuated Vaccines?

Weakened (attenuated) viruses

• Disease: MMR

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🔹Q: What the source (and disease) of Inactivated Vaccines?

Chemically or radiation-inactivated viruses/bacteris

• Disease: Hep. A, Rabies, Polio

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🔹Q: What the source (and disease) of Protein/Toxoid Vaccines?

Purified proteins/toxins from pathogens

• Disease: Typhoid, Cholera, Hep. B

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Types of biotechnology-derived products/Biologics.

4. Nucleic acid – Aptamer, (Pegaptanib sodium; Macugen).

🔹Q: What is an Aptamer?

Aptamers are:

• Short synthetic Single-stranded DNA or RNA molecules

• Specially designed to BIND biological targets such as proteins w/ ⬆HIGH specificity & Affinity.

💭Think: Aptamer = “DNA/RNA antibody-like grabber.”

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🔹Q: What is the source (and disease condition) of Pegaptanib sodium; Macugen?

RNA Aptamer / Single-stranded Nucleic acid (anti-VeGF Aptamer)

• Disease condition:

  • Macular degeneration

  • Neovascular AMD (age-related macular degeneration)

  • Vision loss associated w/ abnormal blood vessel growth

🔹Q: MOA of Pegaptanib sodium; Macugen?

🔑Macugen is an aptamer that acts like a “protein blocker.”

👉It specifically grabs onto VEGF, the protein causing abnormal blood vessel growth in the eye in macular degeneration.

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What is recombinant DNA products (Insulin, Human Growth Hormone).

🔹Q: What is Recombinant DNA (rDNA)?

Genetically engineered DNA created by recombining fragments of DNA from different organisms.

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🔹Q: What are Recombinant DNA (rDNA) products?

Products made using recombinant DNA tech:

• Recombinant Drugs

• Recombinant Vaccines

• Recombinant Enzymes

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🔹Q: What is Insulin?

A hormone made by pancreatic β-cells that allow cells to take up Glucose form the bloodstream for ATP production.

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🔹Q: Before Recombinant Insulin was available, how was insulin obtained?

Cows’ (Bovine) or Pigs’ (Porcine) pancreases.

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🔹Q: Why is Human Insulin preferred?

AA difference can stimulate ALLERGIC responses.

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🔹Q: What is one example of Recombinant Insulin?

Humulin (Eli Lilly)

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🔹Q: What is HGH (Human Growth Hormone)?

A hormone that promotes overall body growth.

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🔹Q: What disease condition is associated with HGH deficiency?

Dwarfism

• caused by insufficient production of HGH by the pituitary gland.

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🔹Q: What was the old source of HGH before Recombinant tech?

HGH was purified from Cadaver pituitary glands.

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🔹Q: What is the NEW source (of Recombinant HGH)?

1. Human HGH gene is isolated

2. Gene inserted into E.coli Bacteria

3. Bacteria produce HGH

4. HGH is extracted & purified

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🔹Q: What are example of Recombinant HGH products?

• Protropin (Genentech)

• Humatrope (Eli Lilly)

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🔹Q: What is the Key concept of Recombinant DNA products?

Recombinant DNA tech inserts human genes into microorganisms (like bacteria) so they can produce human Therapeutic proteins.

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What is monoclonal antibody.

🔹Q: What are Abs?

Abs are proteins produced by the immune system to identify bacteria, viruses, & other foreign substances & help fight them off.

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🔹Q: What are mAbs (monoclonal Abs)?

Abs made by IDENTICAL immune cells that are all CLONES of 1 unique parent cell.

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🔹Q: What is a key characteristic of mAbs (monoclonal antibodies)?

Monovalent affinity = binds to the SAME epitope on an antigen

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🔹Q: What is an Epitope?

Specific part of an ANTIGEN recognized & bound by an antibody.

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🔹Q: What does monovalent affinity mean in monoclonal antibodies?

It means mAbs bind ONE specific epitope/target.

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🔹Q: Why are mAbs useful Therapeutically?

B/c they are ⬆HIGHLY SPECIFIC & Target ONE specific Antigen/epitope.

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🔹Q: Are mAbs considered Biologics?

Yes.

• mAbs = LARGE-molecule biologics produced using biotech.

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🔹Q: mAbs are:

• CLONES from ONE parent cell

• Bind the SAME Epitope

• Have MONOVALENT Affinity

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🔹Q: What is hybridoma technology?

A method used to produce mAbs.

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🔹Q: What cells are used in hybridoma technology?

• Ab-producing B lymphocytes (from immunized mice)

• Immortal Myeloma cells

⭐️These 2 types of cells FUSE TOGETHER → forms HYBRIDOMA cells.

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🔹Q: What is a Hybridoma cell?

A fused cell made from:

• B Lymphocyte + Myeloma cell = Hybridoma cell

⭐️It can continuously produce mAbs.

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🔹Q: What is the end product of hybridoma technology?

mAbs

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🔹Q: Why are Myeloma cells used in hybridoma technology?

Myeloma cells are IMMORTAL → allowing continuous growth & Ab production

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🔹Q: Why are B lymphocytes used in hybridoma technology?

B/c they produce Ab against a specific Ag.

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🔹Q: Why is hybridoma technology preferred for monoclonal antibody production?

B/c the mAbs produced are:

• ⬆High purity

• ⬆Highly sensitive

• ⬆Highly specific

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🔹Q: Hybridoma “formula”:

B cell + Myeloma cell = Hybridoma = mAbs