Nanotechnology and Nanomedicines Flashcards
What is the primary benefit of NanoCrystal technology?
Improve solubility of poorly water soluble drugs
Give 2 examples of water soluble drugs which have been incorporated into nanocrystal technology and their brand name
Rapamune (sirolimus)
Emend (aprepitant, MK 869)
How are NanoCrystals produced?
Proprietary, wet-milling technique creates nanosized drug particles
NanoCrystal particles are stabilised with GRAS particles to prevent clumping
What strengths are Rapamune available in?
0.5, 1, 2mg tablets
1mg/ml oral solution
How is Sirolimus incorporated into Rapamune?
As a NanoCrystal Colloidal Dispersion in which the drug particle size is reduced to nanometre dimensions in the presence of a stabiliser
Describe the layers of Rapamune
Inert tablet core which was previously overcoated with shellac and inert filler coats
Nanodispersion is sprayed onto the inert tablet core, forming the active drug layer
Last layer is the colour coat
Sirolimus is susceptible to oxidative degradation. How is this prevented?
Can degrade when exposed to oxygen and iron oxide based colourants. To prevent this:
- a sucrose seal coat is placed between the active drug layer and the colour coat containing oxides
- alpha tocopherol (vitamin e) is added as an antioxidant
Give 3 examples of synthetic polymers
Polyanhydrides
Poly(alkylcyanoacrylates)
Polyesters e.g. PLGA
Give 4 examples of natural polymers
Albumin
Gelatin
Alginate
Chitosan
Give an example of a polymeric nanoparticle technology
Abraxane - Albumin
(specifically nanoparticle albumin technology)
Indication and API of Abraxane
Paclitaxel
Metastatic breast and pancreatic cancer
How does NAB work in Abraxane?
Drug is coated onto 130nm albumin particles. This provides colloidal stabilisation.
Drug binds on albumin via reversible and non-covalent binding of hydrophobic substances
2 tumour targeting mechanisms
EPR
Active targeting (via gp60)
Size distribution of polymeric micelles
10-80nm
3 micelle mechanisms
- Solubilised in hydrophilic micelle core
- Conjugation to micelle polymer
- Targeting - ligands (antibodies)
Size requirements of Polymeric Micelles
Large enough to avoid renal excretion (>50kDa)
Small enough to avoid MPS (<200nm)
Hydrophilic component of micelles
PEG
Hydrophobic components of micelles
Polyaspartate
Polylactide
Polycaprolactone
Name the 4 drug loading methods in polymeric materials
- Non-specific self assembly
- Drug-initiated polymerisation
- Prodrug monomer co-polymerisation
- Post polymer synthesis functionalization
Give example of polymeric micelle system
Genexol-PM
Paclitaxel for metastatic breast cancer in S. Korea
Examples of anti-cancer drugs used in polymeric-drug conjugates
Doxorubicin
Cisplatin
5-FU
How does galactose targeting system work?
Galactose is a targeting ligand which directs the conjugates to certain cells.
ASGPR (asialoglycoprotein receptor) is selectively expressed on the surface of hepatocytes and hepatomes in the liver. Galactose binds to these.
Not specifically selective for neoplastic tissue
Name the drug, linker and polymer in Oncaspar
L-asparaginase
Amide
m-PEG
Name the drug, linker and polymer in PEG-Asys
interferon alfa-2a
amide
branched m-PEG
