Research and Industrialization of Micro- and Nanosized Carriers of Active Components in Healthrelated Fields Qiang Xia Professor, Ph D State Key Laboratory of Bioelectronics Jiangsu Key Laboratory of Biomaterials and Devices Suzhou Key Lab of Biomedical Materials and Technology School of Biological Science and Medical Engineering Southeast University, China
CV & Research Connection with EU 20+ years experience in fundamental research and industrialization of nanomaterials Establish the first production line of ADS in China 50+ papers published and 20+ patents applied and authorized Adviser of more than 40 Ph D and master students Supplying R&D service for the Cocacola company and many other international and domestic companies Responsible for more than ten national and local scientific projects (over 10 million RMB in total) Visiting Scholar in German supported by DFG (2003) and DAAD (2006) Long-term cooperation relationship with Prof. Dr. Rainer H. Mueller of FU Berlin, Germany International cooperation projects with German partner: National 863 project(2005-2006), International science and technology cooperation project of MOST(2008-2012)
Layout Research Institute of Southeast University in Suzhou R&D Center Industry Partner Engineering Center
Framework of R&D and Indutrilization in SEU State Key lab of Bioeletronics Key lab of biomaterials and devices of Jiangsu Province School of Biological Science and Medical Engineering Suzhou Key Lab Suzhou Institute of Southeast Uni. Suzhou Nanohealth Biotech Company Basic research Applied basic research applied technology Commercializa tion Phase Diagram Controllable Preparation Production technology KEY STEP: large-scale production of LN Products and Markets Indutrilization
Active Delivery System, ADS carrier system for encapsulation of active components based on Drug Delivery System (DDS), extended to the cosmetics, food and other industry fields. Serviceability: water-insoluble/water soluble active components with application difficulty Difficulties: water-insoluble; easy to degrade; chemical labile; lower loading capacity; peculiar smell; irritative Solutions in our labs: nanosized: liposome, micro/nano-emulsion, lipid nanoparticles, cyclodextrin complex, nanosuspension (water-insoluble actives) micron: multiple emulsion, lipid microparticles (water soluble actives) Industry fields: Drug, Food, Cosmetics, any industry using active components
Total View Anti-AIDS ATRA Azithromycin Drug V E Food DHA Cosmetics TP FLN ALA Nanocarriers
Tendency Analysis Cosmetis Industry: Position of ADS upgrade of tradition industry:multidiscipline high-tech industry high-tech materials:raw materials based on high-tech such as nanotechnology GMP production:improve the quality system product tendency:21 century is anti-aging century Creative High-end Raw materials based on High-technology Personalized Product comes from Personalized Material Customer Value increase the technology level of products solution for some excellent active components with application difficulty improve the function and competition
Ten factors for ADS Optimization Loading Capacity Encapsulation Efficiency Physical Stability Chemical Stability Formulation Compatibility Custom special needs Safety Evaluation Function Evaluation Large-scale Production Total Cost
Carrier system of water-insoluble actives Liposome Micro/nano-emulsion Lipid nanoparticles China-EU cooperation 1G: solid lipid nanoparticls (SLN) 2G: nanostructured lipid carriers (NLC) 3G: functional lipid nanoparticles (FLN) Nanosuspension/Nanocrystal Cyclodextrin complex Polymer nanoparticles
Micro/Nanoemulsion transparent or semitransparent, thermodynamic stable system made up by oil phase, aqueous phase, surface active agent and cosurfactant. O/W Bicontinuous W/O Target Actives: VE, VA, Q10, dimethyl silicone oil
Characteristic Advantage Good physical stability, little toxicity, higher lipid content Good bioavailability Large-scale production by using HPH O/W microemulsion: carrier for water-insoluble actives W/O microemulsion: carrier for water-soluble actives Disadvantage Rapid release of active components from the carrier: liquid carrier has less immobilization for actives very small (nanosized) size of carrier Protection ability for actives is relatively weak
Nanoemulsion of Vitamin E t=60 o C water t=60 o C water transparent transparent spc Tween20 SPC+10%V E Tween20+10%V E Project for Cocacola
Lipid Nanoparticles, LN Submicron lipid particles
Lipid Nanoparticles, LN Nanoparticles made of 1/2/more solid/liquid lipids with high biocompatibility Nanosized carriers of active compounds Origin: 1990s and used as nanosized DDS by Prof. Dr. R.H.Mueller Progress: used as nanosized carriers of many active compounds Advantages: Good safety Universal carriers
Platform technology Medicine: nanosized drug delivery system Food: nanosized carriers of nutrients Cosmetics: nanosized carriers of cosmetic active compounds Development Progress: 1G : Solid Lipid Nanoparticles (SLN) 2G : Nanostructured Lipid Carriers (NLC) used as nanosized DDS of lipophilic drugs ---------------------------------------------------------------------------------------- 3G : Functional Lipid Nanoparticles (FLN) expanded to other health-related fields: food/cosmetics
Advantages High stability Almost 100% encapsulation ratio makes active component much longer activity and high stability. High safety Using high biocompatibility glyceride as the main carrier material. High loading capacity achieved by choosing lipid carrier material, emulsifier and processing technique. Change oil into water Change oil-soluble active component into submicron water-soluble dispersion system.
Advantages continued Prolonged release Encapsulation tech on the fundamental of solid lipid carrier has this function to achieve the effect of active component. Compatible to skin Tiny submicron lipid particles has great compatibility with skin to carry the active component into skin s horny layer. Increase the moisture preservation Lipid material could form a good closed system to increase the skin s hydration and improve the cosmetics moisture preservation. left right Eliminate the peculiar smell and decrease the irritation Example: ALA, DHA, glycolic acid
Structure of Submicron Lipid Particle Perfect crystal structure of SLN Three types of NLC: Defect construction, Amorphism and Multiple construction. Crystal condition of SLN and NLC in storage
Industrialization of FLN in Southeast University Past Phase behavior of special hot microemulsions Controllable preparation of FLNs Initial trial for lab-scale production of FLNs Now Large-scale production line Key production technology Product standards Application in cosmetic fields Future Evaluation of safety and functionality Markets and Sales in food & nutrients, DDS
High Pressure Homogenization
Basic Study on Phase Behavior Pseudoternary phase diagram of S- 40/F-68/GMS/Water system at 60 S-40/F-68(7:3) II 1- hob 2-infall pipe 3- sample tube 4-polarizer 5-stirrer 6-box 7-outfall pipe 8-controller IV Schematic Diagram of apparatus with temperature control I III Water GMS
Mean size(nm) Applied Basic: Controllable preparation 14 12 10 8 6 4 2 0 0 d 3 m 6 m 12 m TIME TEM GMS-SLN GMS-SLN
Lab-scale production of FLN (1G, 2006) Aim: increase the production ability from 10 ml grade to 10 L grade realization of 50 L product in one intermittent production Route: Home-made production equipment National 863 Sino-German international cooperation project(2005-2006)
Large-scale Production 2G(2009): 100 KG/batch ( Shown below) 3G(2011): flexible production line (shown below) 4G (now): GMPC production line (under construction) Sino-German International science and technology cooperation project of MOST(2008-2012)
Personnel communication
Personnel communication
Personnel communication a FU of berlin Kelchstr. 31, berlin,germany 2012
Industry summit and exhibition
Actives Involved Anti aging : ALA Q10 VAP VE RES DHA 1789 Complex system: Q10/ALA Q10/V E ALA/V E Q10/ALA/V E Q10/V E /V A V A /V C /V E Sunscreen : UVA+UVB: PARSOL 1789+ MCX/OMC PARSOL 1789+ 303 A PLUS + T150 Dispersed system TiO 2 ZnO Liposome : Q10 RES VE ALA ALA/Q10 ALA/VE Q10/VE Cyclodextrin Complex: RES RES /ALA RES /Q10 Tanshinone Multiple emulsion: VC TP V C /V E Water-locked lipid particles: glycolic acid plant extracts Whitening: arbutin ellagic acid Skin feeling : blank liposome dimethyl silicone oil liposome Essence : lipid nanoparticles lipid particles Drug delivery system: retinoic acid chlormethine hydrochloride Imiquimod Nifeveric
Future cooperation plan with EU In-depth cooperation with industry technology cooperation in all the product development cycle Forward-looking technology development Cosmetics: Nivea in Hamburg, Germany; Univerlever; L 'oreal Functional food and nutrients Drug delivery system Joint research and development institutions in EU or China Joint venture company in EU or China
Research Team in Suzhou Division
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