Lipid Based Drug Delivery Flashcards
(25 cards)
What are challenges in drug delivery?
- Limited aqueous solubility (lipophilic drugs)
- Sensitive peptide, proteins and DNA drugs
- Challenges keeping them stable during drug delivery
- Only active against specific biological targets e.g. cell receptors
- Significant cytotoxicity (e.g. anti cancer drugs)
- Require specific intracellular target (e.g. nucleus - DNA drugs)
What are the Aims of Drug Delivery Systems?
- Creation of new pharmaceutical moieties
- Improve effectiveness
- Reduce side-effects
- Extension of patent lifetime of an agent currently in market
What are the 2 Challenges of the Biopharmaceutical Classification System?
- Solubility
- Permeability
- Getting drugs across biological barrier
What Strategies do we use to Improve Absorption?
- Physical modification e.g. for solid dosage forms:
- Particle size
- Crystalline behaviour
- Chemical modification
- Pro-drug (e.g. more lipophilic, more water soluble)
- Modify e.g. PEG salt
-
Reformulate into a carrier system
- Non-colloidal
- Colloidal
- Polymer
- Inorganic
- Lipid based
What are the Desired Properties of a Drug Delivery System?
- Biocompatibile (non-toxic)
- Protect drug until it reaches active site
- Drug-carrier integrity
- Cell-drug interaction
- Cross biological membranes to get to target site
- Target recognition
- Controlled drug release
- Carrier elimination from body
Why use Lipids?
- Natural - biocompatible
- Non-toxic
- Facilitates crossing biological barriers (interaction with those biological barriers)
- Protective action
- Protect encapsulated actives from the aqueous environments and oxidation etc
- Effective encapsulation
- Can mimic biology
What is the Fatty Food Effect?
- Increased solubilisation of poorly water soluble compounds
- Reduce metabolism/efflux
- Increase membrane permeability
- Stimulation of intestinal lymphatic transport
- Protection against intestinal proteases and surfactants
What is an Emulsion?
A dispersion of one liquid in another liquid
e.g. lipid oil in water
Macroemulsion
- Drop size range?
- Influence of gravity?
- Stable?
- Surfactant concentrations used?
- Energy required?
- Drop size range > 0.1 mcm
- Droplets typically settle under influence of gravity
- Thermodynamically unstable
- Typically low surfactant concentrations used
- Energy is required to prepare macroemulsions
What are the Methods of Lipid Emulsion Preparation?
- Shaking
- Injection
- Jet Impact
- Stirring
- Colloid Mill
- Ultrasonic
- Electrical
- Condensation
- High pressure homogeniser
What is the Point of Emulsion Stabilisation?
How do you Stabilise Emulsions?
- Use stabilisers to keep droplets small
- Charge Stabilisation
- Put surfactants that have positive or negative charge and they keep the droplets in a repulsive state
- Steric Stabilisation
- Use things like polymers
- Pickering Emulsions
What are the Therapeutic Applications of Lipid Emulsions?
- Solubilisation of lipophilic drugs
- Stabilisation of hydrolytically susceptible compounds
- Prevention of drug uptake by infusion sets
- Reduction of irritation, pain or toxicity
- Potential for sustained release
- Targeted delivery
What a Liposomes?
- Created through phospholipids which form a lipid membrane
- Can be made in a controlled way and very small
What are Characteristics of Liposome based Drug Delivery?
- Controlled delivery system
- Biodegradable, Non-Toxic
- Carry both water and oil soluble payloads
- Prevention of oxidation
- Protein stabilisation
- Controlled hydration
What are the Types of Targeted Drug Delivery of Liposomes?
- Adsorbed polymers for modifying circulation time and controlling drug release
- Modify circulation time e.g. PEGylated lipids
- Functional lipids e.g. cationic vs. anionic head groups, prodrug lipids
- Targeting functionality e.g. protein, antibody that will recognise receptors in the body
What are Stealth Carriers?
- Modification with PEG for:
- Reduce RES recognition
- Increased circulation time
- Reduced toxicity
- Passive delivery
What is Passive Delivery of Therapeutic Agents?
e.g. if you have a tumour?
- The tight junctions are known to be leaky around tumours
- Design liposomes that are PEGylated so that when they’re in a vicinty of a tumour, they can be passively diffuse through biological membrane
- Delivery system’s physiochemical and surface characteristics tailored to physiology of target site (no specific biological interactions utilised)
What are the 2 types of Stimulated Targeting of Therapeutic Agents?
- Internally Stimulated:
- A specific biochemical interaction facilitates release and delivery
- Externally Stimulated:
- Temperature, light, ultrasound, magnetic fields
Many poorly water soluble drugs show a positive food effect and have?
- Low and variable bioavailability
- Poor patient compliance
Lipid based delivery offers improved solubilisation and absorption. However:
- Solid dosage forms aren’t optimal
- Food effect not optimal
Why are lipid emulsions attractive delivery systems for poorly soluble drugs?
Because of the fatty food effect
What are the Challenges in developing lipid based pharma products?
- Instability
- Dose Control
- Digestion not optimally controlled
- Poor in vitro-in vivo correlation
- Not readily formulated as solid dosage forms
What way can nanoparticle coatings be engineered for improved performance of lipid droplets?
- Emulsification and dispersion stability
- Reduce chemical surfactant levels
- Long term physical stability
- Enhance chemical stability of encapsulated active ingredient
- Controlled release
- Enhanced delivery performance
What are Advantages of SLH over conventional solid carriers?
- Highly modular - engineered with specific properties for specific drugs
- Highly efficient pore loading and release in comparison to many lipid loadable porous particles
- Novel MOA - mimicking and optimising the pharmaceutical food effect
