BG4231&BG6001-Lect 2- Formulation and patterning of biomaterials.pdf

Formulation and patterning of biomaterials Lecture 2 Formulation and patterning of biomaterials Asst. Prof. Dang Thuy Tram [email protected] Office N1.3-B3-09 BG 4231/BG6001 – Advanced Biomaterials 1 Formulation and patterning of biomaterials Lecture Outline 1. Microparticles : materials, me...

Formulation and patterning of biomaterials Lecture 2 Formulation and patterning of biomaterials Asst. Prof. Dang Thuy Tram [email protected] Office N1.3-B3-09 BG 4231/BG6001 – Advanced Biomaterials 1 Formulation and patterning of biomaterials Lecture Outline 1. Microparticles : materials, methods, types, applications 2. Sub-micron/Nanoparticles : micelles and liposomes & their applications 3. Hydrogels: classifications, synthesis, patterning and applications 2 Formulation and patterning of biomaterials Why do we need micro/nanoparticulate formulation of biomaterials? • Advantages of micro/nanosized systems  Small size compared to surgical implants  High surface area allowing for surface functionalization  Ability to carry fluorescent molecules  Unique ability to interact with cells and cellular component Nanoparticles Sub-micro/Nanoparticles Microparticles https://www.particlesciences.com/news/technical-briefs/2012/glossary-of-drug-nanotechnology.html 3 Formulation and patterning of biomaterials Microparticles Polymeric materials used for microparticle preparation • Synthetic polymers  Aliphatic polyester (PLGA, PLA, PGA)  Poly(caprolactone) (PCL)  Poly(ortho esters) (POE) • Naturally derived polymers  Chitosan  Gelatin  Alginate  Hyaluronic acid Park J. et al Molecules., 2005 4 Formulation and patterning of biomaterials Microparticles Methods for preparation of microparticles Single and double emulsion solvent evaporation Xu Q. et al Small., 2009 5 Formulation and patterning of biomaterials Microparticles Methods for Preparation of microparticles Flow-focusing microfluidics um um Xu Q. et al Small., 2009 6 Formulation and patterning of biomaterials Microparticles Methods for Preparation of microparticles Spray drying 7 Formulation and patterning of biomaterials Microparticles Methods for Preparation of microparticles Ionic gelation 8 Formulation and patterning of biomaterials Microparticles Variety of polymeric microparticles Campos E. et al Eur. Polymer J., 2013 Janus microparticles Crescent moon-shaped microparticles Porous microparticles Zhang GH et al, Chi. Chem. Lett 2013. Hu J et al Chem Soc Rev. 2012 Kim SH et al, JACS 2011. 9 Formulation and patterning of biomaterials Microparticles Applications of polymeric microparticles http://msne.knu.ac.kr/knu_builder/reserch/research14.htm 10 Formulation and patterning of biomaterials Nanoparticles Definition & Size comparison Talelli et al, Nano Today 2015 11 Formulation and patterning of biomaterials Nanoparticles – Liposomes Definition of liposomes • “Liposome” is a sphere-shaped vesicles consisting of one or more phospholipid bilayers enclosing an aqueous volume. Transmission Electron Microscopy image of a liposome 12 Formulation and patterning of biomaterials Nanoparticles – Liposomes Phospholipid in cell membrane http://teachmephysiology.com/basics/cell-structures/cell-membrane/ 13 Formulation and patterning of biomaterials Nanoparticles – Liposomes Cholesterol in cell membrane • Cholesterol decreases membrane fluidity at high temperature (>Tm) due to hindered movement of the hydrophobic chains https://iweb.langara.bc.ca/biology/mario/Biol2415notes/biol2415chap7.html • Cholesterol increases membrane fluidity at low temperature (<Tm) by disrupting the close packing of the hydrophobic chains 14 Formulation and patterning of biomaterials Nanoparticles – Liposomes Cholesterol (< 50%) Materials for preparation of liposomes Phospholipid L-α-phosphatidylcholine, composed of fatty acid chains, glycerol backbone and the headgroup (choline) Interaction between phospholipid and cholesterol O “Bending” of fatty acid chains increase inter-chain spaces Monteiro N. et al Interface., 2014 https://www.youtube.com/watch?v=04SP8Tw3htE 15 Formulation and patterning of biomaterials Nanoparticles – Liposomes Structure of liposomes Thermodynamically driven formation of liposomes Monteiro N. et al Interface., 2014 16 Formulation and patterning of biomaterials Nanoparticles – Liposomes Properties of liposomes Selective permeability Monteiro N. et al Interface., 2014 17 Formulation and patterning of biomaterials Nanoparticles – Liposomes Properties of liposomes Effects of temperature and cholesterol on phospholipid bilayer permeability Monteiro N. et al Interface., 2014 18 Formulation and patterning of biomaterials Nanoparticles – Liposomes Classification of liposomes 0.1-15µm 1.6-10.5µm Monteiro N. et al Interface., 2014 • Classification is commonly based on the number of bilayers and vesicles  ULVs : uni-lamellar vesicles  MLVs : multi-lamellar vesicles  MVV : multi-vesicular vesicles • Based on their size, unilamellar liposomes are classified as  large unilamellar vesicles (LUVs, 100 nm-1 µm) or  small unilamellar vesicles (SUVs, 25– 50 nm) 25 nm-1 µm 19 Formulation and patterning of biomaterials Nanoparticles – Liposomes Method for preparation of liposomes Thin film hydration followed by extrusion • Different MLVs can be produced depending on  the hydration time  the re-suspension method  the lipid concentration and composition  the volume of the suspending aqueous phase • Advantages : Best quality and stability for cationic liposomes • Disadvantages :  Low encapsulation efficiency  Difficulty in producing nanosized liposomes Andhale VA. et al Int. J. Pharm & Tech.., 2016 https://www.youtube.com/watch?v=vGz-qDE3Go4 20 Formulation and patterning of biomaterials Nanoparticles – Liposomes Methods for preparation of liposomes Thin film hydration followed by extrusion • Obtain liposome of smaller sizes after each extrusion https://www.youtube.com/watch?v=vGz-qDE3Go4 21 Formulation and patterning of biomaterials Nanoparticles – Liposomes Functionalization of liposomes conventional liposomes sterically stabilized liposomes fluorescent/charged liposomes ligand-targeted liposomes Monteiro N. et al Interface., 2014 • Lipid nanoparticles carrying nucleic acids such as mRNA, DNA, siRNA 22 Formulation and patterning of biomaterials Nanoparticles – Liposomes & lipid nanoparticles Applications of liposomes Approved and marketed drug-loaded liposomal products Product Drug Indications Year approved AmBisome (Gilead) Amphotericin B Fungal infections Leishmaniasis, Kaposi's sarcoma Ovarian cancer Multiple myeloma + Velcade Kaposi's sarcoma 1990 (Europe), 1997 (USA), 2000 1995 1999 (Europe, Canada) 2007 Doxil/Caelyx (Johnson Doxorubicin & Johnson) DaunoXome (Galen) Daunorubicin Myocet (Cephalon) Doxorubicin Amphotec (Intermune) Amphotericin B Abelcet (Enzon) Amphotericin B Visudyne (QLT) Verteporphin DepoDur (Pacira) DepoCyt (Pacira) Diprivan (AstraZeneca) Estrasorb (King) Lipo-Dox (Taiwan Liposome) Morphine sulfate Cytosine Propofol Estrogen Doxorubicin Marqibo (Talon) Vincristine mRNA vaccines Pfizer, Moderna Breast cancer + cyclophospha mide Invasive aspergillosis Aspergillosis Wet macular degeneration Pain following surgery Lymphomatous Anesthesia Menopausal therapy Kaposi's sarcoma, breast and ovarian cancer Acute lymphoblastic leukemia Covid-19 1996 (Europe), 1996 (USA) 2000 (Europe) 1996 1995 2000 (USA), 2003 (Japan) 2004 1999 1986 2003 2001 (Taiwan) 2012 (USA) 2020 Allen TM. et al Adv Drug Delivery Review., 2013 23 Formulation and patterning of biomaterials Nanoparticles – Liposomes & lipid nanoparticles Applications of liposomes 24 Formulation and patterning of biomaterials Hydrogels Definition of hydrogels • “Hydrogels” are polymeric structures held together as water-swollen gels by  Primary covalent cross-linking  Ionic forces  Hydrogen bonds  Affinity or bio-recognition interaction  Hydrophobic interaction  Polymer crystallites  Physical entanglement of individual polymer chains https://www.slideshare.net/kegranger1/  Combination of 2 or more factors above hydrogel-53634746 https://www.extremetech.com/extreme/215033-new-hydrogelcan-keep-stem-cells-alive-for-heart-repair Buenger D. et al Progress. Polymer Sci., 2012 25 Formulation and patterning of biomaterials Hydrogels Classification of hydrogels Based on type of crosslinking Hoffmann A. et al Adv. Drug. Del. Rev.., 2001 Type of crosslinking Relative bond strength in water (kcal/mol) Covalent gel ~100-200 Ionic ~5 Hydrogen bonding ~1-2 (in polar solvent) Polypeptide complexation ~1-10 Hydrophobic interaction ~1 • Alternative classification methods based on  Charge characteristics  Method of preparation  Degradability 26 Formulation and patterning of biomaterials Hydrogels unreacted functionality Structure of a hydrogel network chain loops multifunctional junctions entanglement • Hydrogels with ideal network are rarely observed • Network defects are common and affect hydrogel properties 27 Formulation and patterning of biomaterials Hydrogels Synthesis of hydrogels By free radical polymerization/cross-linking 28 Formulation and patterning of biomaterials Hydrogels Synthesis of hydrogels By cross-linking with small multifunctional molecules (cross-linkers) 29 Formulation and patterning of biomaterials Hydrogels Synthesis of hydrogels By forming interpenetrating hydrogel network 30 Formulation and patterning of biomaterials Hydrogels Synthesis of hydrogels By ionic interaction or affinity recognition 31 Formulation and patterning of biomaterials Hydrogels adopted from microelectronic industry Patterning of hydrogels Soft lithography Step 2: Micromolding of prepolymer into cross-linked hydrogel Step 1 : Fabrication of PDMS mold Subramani K D. et al Emerg. NanoTech. Manufacturing 2010 https://www.elveflow.com/microfluidictutorials/soft-lithography-reviews-and-tutorials/ 32 Formulation and patterning of biomaterials Hydrogels Patterning of hydrogels Example of PEG-DA hydrogel patterning Subramani K D. et al Emerg. NanoTech. Manufacturing 2010 33 Formulation and patterning of biomaterials Hydrogels Patterning of hydrogels Example of 3D printing of hydrogel/polymer - Type of materials : synthetic and natural hydrogels - 3D printing methods : (i) Laser-based systems by virtue of photopolymerization (ii) Nozzle-based systems through extrusion of (pre)polymers (iii) Ink-jet printing Laser-based system Ink-jet system https://www.youtube.com/watch?v=lSDJkcwmpuI Extrusion system Li. et al Mat Sci & Eng Reports 2020 34 Formulation and patterning of biomaterials Hydrogels Applications of hydrogels • Drug delivery systems • Hygiene products (diapers) • Opthamologic products (contact lens, intra-ocular lenses) • Surgical sealants • Dermal care products (wound dressings) • Tissue Engineering • Cell encapsulation applications 35 Formulation and patterning of biomaterials Summary 1. Microparticles : materials, methods, types, applications 2. Sub-micron/Nanoparticles : micelles and liposomes & their applications 3. Hydrogels: classifications, synthesis, patterning and applications 42