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

Research and Industrialization of Micro- and

Nanosized Carriers of Active Components in Health-

related Fields

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）

CV & Research Connection with EU

Layout

R&D Center

Industry Partner Engineering Center

Research Institute of Southeast

University in Suzhou

Phase Diagram

Basic research

Controllable Preparation

Applied basic research

Production technology

applied technology

Commercialization

KEY STEP: large-scale

production of LN

Framework of R&D and Indutrilization in SEU

Products and Markets

Suzhou Key Lab

Suzhou Institute of

Southeast Uni.

Suzhou

Nanohealth

Biotech

Company

State Key lab of Bioeletronics

Key lab of biomaterials and devices of

Jiangsu Province

School of Biological Science and

Medical Engineering

Indutrilization

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

Active Delivery System, ADS

Nanocarriers

FLN

Anti-AIDS

Azithromycin

ATRA

TP

ALA

DHA

VE

Drug

Food

Cosmetics

Total View

Cosmetis Industry：

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

Position of ADS

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

Tendency Analysis

Loading Capacity

Encapsulation Efficiency

Physical Stability

Chemical Stability

Formulation Compatibility

Custom special needs

Safety Evaluation

Function Evaluation

Large-scale Production

Total Cost

Ten factors for ADS Optimization

Liposome

Micro/nano-emulsion

Lipid nanoparticles

1G: solid lipid nanoparticls (SLN)

2G: nanostructured lipid carriers (NLC)

3G: functional lipid nanoparticles (FLN)

Nanosuspension/Nanocrystal

Cyclodextrin complex

Polymer nanoparticles

Carrier system of water-insoluble actives

China-EU cooperation

transparent or semitransparent, thermodynamic stable system made up by oil

phase, aqueous phase, surface active agent and cosurfactant.

Micro/Nanoemulsion

O/W

Bicontinuous

W/O

Target Actives:

VE, VA, Q10, dimethyl silicone oil

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

Characteristic

Nanoemulsion of Vitamin E

Tween20

water

spc

transparent

t=60oC

water

Tween20+10%VESPC+10%V

E

transparent

t=60 oC

Project for Cocacola

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

Lipid Nanoparticles, LN

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

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

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.

Eliminate the peculiar smell and decrease the irritation

Example: ALA, DHA, glycolic acid

Advantages continued

left rightleft right

Structure of Submicron Lipid Particle

Three types of NLC: Defect

construction, Amorphism and Multiple

construction. Perfect crystal structure of SLN

Crystal condition of SLN and

NLC in storage

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

Industrialization of FLN in Southeast University

High Pressure Homogenization

Basic Study on Phase Behavior

①- hob ②-infall pipe ③- sample tube ④-polarizer

⑤-stirrer ⑥-box ⑦-outfall pipe ⑧-controller

Schematic Diagram of apparatus with temperature control

S-40/F-68(7:3)

Water GMS

II

I

III

IV

Pseudoternary phase diagram of S-

40/F-68/GMS/Water system at 60℃

Applied Basic: Controllable preparation

0

2

4

6

8

10

12

14

0 d 3 m 6 m 12 m

TIME

Mean size（

nm）

GMS-SLN TEM GMS-SLN

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

Lab-scale production of FLN (1G, 2006)

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/VE ALA/VE Q10/ALA/VE Q10/VE/VA VA/VC/VE

Sunscreen ：

UVA+UVB: PARSOL 1789+ MCX/OMC

PARSOL 1789+ 303

A PLUS + T150

Dispersed system TiO2 ZnO

Liposome ： Q10 RES VE ALA ALA/Q10 ALA/VE Q10/VE

Cyclodextrin Complex： RES RES /ALA RES /Q10 Tanshinone

Multiple emulsion： VC TP VC/VE

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

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

Future cooperation plan with EU

Research Team in Suzhou Division

Thank you for your cooperation!