Quiz 2: Metals and Alloys & Ceramics and Glasses/ Drug delivery Flashcards
Alloy
comprised of two or more elements, at least one is metallic
Ways metals mix
substitutional
interstitial
Solvent and solute in alloys
The more abundant element is referred to as the solvent, and the less abundant element is the solute.
Substitutional Alloys
one element replaces another at the original location
Conditions for substitutional solid solutions (alloys)
The atomic radii of the two elements similar (<=15%)
Their lattice types must be the same
The lower valency metal becomes the solvent
Crystalline architecture
Body-centered cubic: ductile, plastic, more workable
Face-centered cubic: ductile, plastic, workable
Hexagonal-close packed: lack plasticity
Substitutional Alloys examples
Dental alloys: Gold silver (crowns & bridges), silver copper (admixed dental amalgam), silver tin (low copper dental amalgam)
nickel-titanium (superelastic wires)
Interstitial Alloys
one element dispersed between, elements located in spaces between atoms in the unit cell
The solubility depends on the size of these gaps and the crystal structure.
important interstitial solute atoms: C, H, B, N, O
radii has to be <=59%
Alloys in use
permanently implantable: intended for indefinite use within the body (ex. stainless steels, cobalt-chromium-molybdenum, titanium)
biodegradable alloys: designed to be temporary, degrading, or bio-corroding over time (Mg)
Glass
inorganic product of fusion cooled to a rigid condition without crystallization, amorphous solid
Types of bio-ceramics- tissue interactions
morphological fixation
biological fixation
bioactive fixation
morphological fixation
dense, inert, nonporous ceramics attach to bone or tissue growth into surface irregularities by press fitting into a defect as a type of adhesive bond
biological fixation
porous inert ceramics attach by bone resulting from ingrowth into pores resulting in mechanical attachment of bone to material
bioactive fixation
dense, nonporous surface-reactive ceramics attach directly by chemical bonding with bond
Alumina and zirconia applications
Modular heads on femoral stem hip components, wear less than metal components
Calcium phophates
direct bond with bone tissue, biological apatites which constitute the principal inorganic phase in moral calcified tissues are carbonate hydroxyapatite
Calcium hydroxyapatite
(Ca10(PO4)6(OH)2)
Ca2+ ions surrounded by PO43- and OH- ions
Motivation for drug delivery system
provide stability and localization of drugs
enhance or enable drug efficacy (small molecule drugs, nucleic acids and proteins)
Challenges in drug delivery route across biological barrier
stability and permeability (change in pH, passing through mucus layer)
Drug release profiles
immediate release systems
first-order release systems: little bit of control in modulating drug release
zero-order release systems
Mechanisms of drug release
Diffusion
Degradation
Prodrug cleavage
Affinity-based release
Reservoir-based prolonged release
Degradation & dissolution-mediated release
DDss for drug targeting
Passive targeting: relies on physicochemical properties of the carrier (size, charge, shape), surface modification with poly(ethylene glycol) has shown to enhance circulation time and improve targeting
Active targeting: achieved through specific interactions by ligands on DDs
Microparticles (MPs)
provide extended duration of action, reduced systemic toxicity, and improved patient compliance
can be fabricated from natural or synthetic polymers
used in drug delivery, molecular imaging, and immune adjuvants
1 - 1000 um
Particle size
MPs tend to be depot formulations, taken orally, inhaled, or injected in tissue to achieve effects locally
Larger particle limitation
larger vehicles cannot be delivered directly into the circulation (eg. intravenously) bc of concerns over obstruction of blood vessels
more likely to clog needles or settle in a solution intended for injection
less likely to penetrate into cells than nanoparticles
MP preparation
1) single and double emulsion
2) coacervation phase separation
Single and double emulsion
emulsification followed by solvent evaporation
D-F: double emulsion system (hydrophillic, protein drug)
F1: solvent evaporation, F2: extraction
A-C: single emulsion system (use if not soluble in water)
F1: solvent evaporation, F2: extraction
Coacervation phase separation
Relies on the changes in solubility of polymers, leading to phase separation and micro-particle formation
relatively high loading efficiency, can be operated at low temp, suitable for sensitive drugs like insulin
Coacervation phase separation example
Encapsulation of proteins into PLGA MP
PLGA dissolved in methylene chloride. aq solution of albumin dispersed in PGLA solution leading to formation of albumin droplets
polymer (silicone oil) with PLGA solution added to dispersion, causing formation of PLGA droplets and absorption onto surface of albumin droplets
Nanoparticles
1-1000 nm
hold promise to revolutionize medical treatment with more potent, less toxic, and smart therapeutics
Surface-to-volume ratio (apply to MP and NP)
smaller particles release drugs quicker, water penetrates particles more rapidly which accelerates drug release and degradation
Polymeric NPs
formed by self assembly driven by hydrophobic interaction, generating hydrophobic core surrounded by a hydrophilic shell (polyermic micelles (20-200nm) nanospheres (100-200nm)
Lipid-based NPs: Liposome
class of nano or micrometer sized phospholipid vesicles composed of one or multiple lipid bilayers that envelope the inner aqueous cores (where the drug is), 25nm-2.5um
Lipid-based NPs: Solid lipid NPs (lipospheres)
consists of lipid matrix that remain in the solid state coated with a monolayer of phospholipid, 50-1000nm
Lipid-based NPs: lipoplexes
cationic lipids can condense negatively charged nucleic acids at particular weight ratios to form nano complexes,
Inorganic NPs: gold
for diagnosis and drug delivery
gold core is inert with low toxicity, monodispersed GNPs are easy to synthesize
1-150nm
Inorganic NPs: magnetic NPs
for MRI contrast agents and nanocarriers for targeted drug delivery
Ex.iron oxide (Fe3O4)
Bio-inspired NPs
Exosomes are inherent carriers of genetic and proteomic information and are believed to be a central form of cell-cell communication
Bio-inspired NPs: protein NPs
amenable to surface modification due to abundant functional groups (carboxylic and amino groups) on NP surface
ex. gelatin, collagen, albumin, elastin
Bio-inspired NPs: DNA nanostructures
designed by precise self-recognization of A-T and C-G pairings, can be degraded by DNase in tissues
Hybrid NPs: cell membrane-coated NPs
synthetic nanoparticulate core cloaked with a layer of natural cell membrane, purpose is to have long circulation and disease-specific targeting
ex. red blood cells membrane coating prolongs the blood circulation of NPs, white blood cells membrane coating enable site-specific targeting of the vasculature of tumors or inflammatory tissues
Gene therapy
Biomaterial used needs to have a positive charge (nucleic acids are negative)
Polycations for construction of gene delivery NPs
PLL, chitosan, PBAE, DMAEMA, Dendrimer (PAMAM), beta-cyclodextrin-containing polycation, PEI
Cell-penetrating peptides for gene delivery
Adopt an inherent helical structure or form a helix during membrane penetration which strengthens the interactions with cell membranes to facilitate cellular internalization
Which of the following is an application for metal biomaterials?
Bone and joint replacement
Dental Implants
Intravascular stents
All of the above
All of the above
True or false: Any combination of elements can form a substitutional alloy as long as one is a metal
False
Which of the following is false regarding interstitial alloys?
The solute atoms should be <=59% of the solvent atoms’ atomic radius
Common interstitial solute atoms include gold, platinum and mercury
Solute atoms are located in spaces between atoms in the unit cell
Steel (iron and carbon) is an example of an interstitial alloy
Common interstitial solute atoms include gold, platinum and mercury
Which of the following alloys would be most suitable for a biodegradable stent?
Stainless steel
Colbalt-Chromium-Molybdenum alloy
Magnesium alloys
Titanium alloys
Magnesium alloys
What is not an advantage of ceramics?
High wear resistance
High modulus
Bioactive in the body
High fatigue resistance
High fatigue resistance
True or false: alumina and zirconia are the two most commonly used structural bioceramics.
True
What is the primary structural component of bones?
Hydroxyapatite
Tricalcium phosphate
Octacalcium phosphate
Zirconia
Hydroxyapatite
True or false: Interatomic bonding in ceramics is either ionic or covalent
True
What is not an application of ceramics?
Bone, plates, screws
Orthodontics
Dental restorations
None of the above
None of the above
Which of the following is an advantage of using nanoparticles in drug delivery?
Increased drug stability
Reduced drug solubility
Increased clearance from immune system
Faster degradation in the body
Increased drug stability
Which material is commonly used for constructing biodegradable microparticles for drug delivery?
Gold
Poly(lactic-co-glycolic acid) (PLGA)
Silver
Silicon dioxide
Poly(lactic-co-glycolic acid) (PLGA)
What is the primary reason PEGylation (adding PEG) of nanoparticles?
To increase drug degradation
To reduce drug absorption
To increase circulation time by evading immune clearance
To improve the particle’s magnetic properties
To increase circulation time by evading immune clearance
Which of the following best describes the term “targeted drug delivery”?
Delivering drugs at a constant rate throughout the body
Delivering drugs specifically to a disease tissue or organ
Delivering drugs uniformly across all tissues
Delivering drugs based on body temperature
Delivering drugs specifically to a disease tissue or organ
In a swelling-controlled release system, what triggers the release of the drug?
Erosion of the outer layer
Absorption of water into the matrix causing it to expand
Diffusion through a membrane
Degradation of the drug molecules by enzymes
Absorption of water into the matrix causing it to expand
Which of the following is a common route of administration for nanoparticle-based drug delivery systems?
Intravenous injection
Oral ingestion only
Inhalation only
Topical application only
Intravenous injection
Microparticles are generally used in drug delivery systems for what purpose?
To provide immediate drug release
To enhance long-term, controlled release of the drug
To limit drug exposure to specific parts of the body
To increase the drug’s molecular weight
To enhance long-term, controlled release of the drug
True or false: nanoparticles in drug delivery systems can improve the solubility of hydrophobic drugs.
True
True or false: microparticles are preferred for drug delivery because their larger size helps them cross the blood-brain barrier
false
True or false: nanoparticles’ higher surface area-to-volume ratio enables more efficient drug loading and release than microparticles
True
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