1. Designs of adipocyte-specific binding microgel for fat reduction
대학원 세미나
Designs of adipocyte-specific binding microgel for fat reduction
Keum-Yong Seong
Supervised by Prof. Seung Yun Yang
Functional Soft Nanomaterials Lab.

2. High-intensity focused ultrasound (HIFU)
Physical therapeutics for fat reduction
High-intensity focused ultrasound (HIFU)
Lasers
Radiofrequency (RF)
Selectively absorption in certain parts of the tissue, depending on color and penetration depth
Ablative lasers, Fractional CO2 lasers
Inducement of complete coagulation necrosis of a targeted tissues
Need of imaging system for safe applications
Temp.: oC
A form of electromagnetic energy (300 MHz – 3 KHz) for selective thermolysis (inducement of apoptosis in fat tissues)
Temp.: 39 – 43 oC
K. Fritz et al., Facial Plast. Surg., 32, 2016
Functional Soft Nanomaterials Lab.

3. PPC injection for fat reduction
Phosphatidylcholine (PPC) and deoxycholate (DCA) compound for efficiently reducing fat tissue
PPC : lecithin, main constituent of beans (a class of phospholipids)
Side effects
Skin ulcer
Bruise
DCA : a detergent for dissolution of PPC (one of the secondary bile acid)
Deoxycholate induces the DNA damage.
DNA damage can give rise to cancer by causing mutations.
Excessive administration of PPC can destroy the muscle and blood vessels.
Functional Soft Nanomaterials Lab.

4. Lipolytic drugs Caffeine Isoproterenol Mechanism of lipolysis
induced by lipolytic drugs
Lipolytic drug
Isoproterenol
Functional Soft Nanomaterials Lab.

5. Mechanism for lipolysis
Polymeric carriers for lipolytic drugs
Concept
Mechanism for lipolysis
Features
Nanoparticles
(NPs)
Drug loaded NPs (liposome, nanosphere, micells…) can transport into the adipocyte by endocytosis.
Particle size : < 100 nm
In situ hydrogel
Sustained drug delivery from 3D network structure of hydrogel
Binding of released drug to β-receptor of adipocyte  Lipolysis
Lipolytic drug
Development of carriers binding to adipocytes is required to increase the efficiency of drug delivery for lipolysis.
Functional Soft Nanomaterials Lab.

6. Adipocyte-specific binding microgel
Approach for carriers to delivery the lipolytic drug
Criteria for carriers to delivery the lipolytic drug
High biocompatibility
Large contact area between adipocytes and carriers
High adhesion between adipocyte and carriers
Sustained drug delivery for maintaining the therapeutic levels
Adipocyte
Adipocyte-specific binding microgel
Designs
Biopolymer based carriers
Spherical particles < sheet-type particles
Targeting of adipocyte-specific site
Hydrogel for sustained drug delivery
MICROGEL
Functional Soft Nanomaterials Lab.

7. 1. Candidates materials for fat reduction 2. Fabrication of microgel
3. Method for adipocyte-specific binding
Functional Soft Nanomaterials Lab.

8. Chitosan as a fat binder
Chitosan as a candidate to inhibit adipogenesis
Chitosan
Chitosan as a fat binder
Natural polymer made by treating the chitin shells of shrimp or crap with an alkaline substance (deacetylation)
Properties
High biocompatibility & biodegradability
Muco-adhesion
Chitosan carries a positive charge on the acetyl remnants and, when solubilized in an acid environment.
the chitosan can bind to negatively charged molecules such as fats and lipids.
Stomach
(pH 2~5)
Functional Soft Nanomaterials Lab.

9. Chitosan as a candidate to inhibit adipogenesis
Anti-obesity effect of chitosan in 3T3-L1 adipocyte
Lipolysis
Adipogenesis
Significantly decreased triglyceride accumulation
Inhibited PPARγ, C/EBPα by chitosan treatment  inhibition of adipogenesis
E. J. Cho et al., J. Microbiol. Biotechnol., 18, (2008)
Functional Soft Nanomaterials Lab.

10. Extracellular matrix components for fat reduction
Extracellular matrix (ECM)
Proteoglycans
Collagen
Reported that ingestion of diets containing gelatin or collagen protein affects the blood levels of triglycerides (TG) and/or total cholesterol (TC) in rats (Saito et al., 2009), mice (Oliveira et al., 2001), and rabbits (Terpstra et al., 1983).
Functional Soft Nanomaterials Lab.

11. Chondroitin sulfate (CS)
Extracellular matrix components for fat reduction
Hyaluronic acid (HA)
Chondroitin sulfate (CS)
Mw of HA : 2000 kDa
HA was shown to regulate adipogenesis through reduction of the expression of genes such as C/EBPα and PPARγ, leading to down-regulation of SREBP-1c and FASN expression in 3T3-L1 cells and finally reduced lipid accumulation.
Mw of CS : 90 kDa
CS inhibited activity of pancreatic lipase.  inhibition of absorption of fatty acids and monoglycerides (fatty acids and monoglycerides are formed by hydrolysis of pancreatic lipase)
B.-G. Park et al., Biochem. Biophysi. Res. Commun., 467, (2015)
L.-K. Han et al., Int. J. Obesity, 24, (2000)
Functional Soft Nanomaterials Lab.

12. M. C. Gannon et al., Am. J. Clin. Nutr., 76, 2002
Gelatin as a candidate to induce lipolysis
Gelatin
A natural biopolymer derived from collagens
Gelatin (Mw: K)
Heating (denaturation)
Collagen (Mw: 300K)
Glycine treated group
Glycine
Gelatin consists of 30% glycine residues.
Glycine can induce lipolysis as increased glucagon concentration in blood.
M. C. Gannon et al., Am. J. Clin. Nutr., 76, 2002
Functional Soft Nanomaterials Lab.

13. 1. Candidates materials for fat reduction 2. Fabrication of microgel
3. Method for adipocyte-specific binding
Functional Soft Nanomaterials Lab.

14. Microtransfer molding method
Microgels fabricated by microtransfer molding method
Microtransfer molding method
Coating of hydrogel precursor on the PDMS mold after degassing in a vacuum chamber
Scraping away excess material
Pressing the agarose slab containing the gelling agent
Floating
G. T. Franzesi et al., J. Am. Chem. Soc., 128, (2006)
Functional Soft Nanomaterials Lab.

15. Microgels fabricated by stop flow lithography
UV source on
Mask
Hydrogel precursor
Hydrogel
Device
Flow
UV source off
Mask
Hydrogel precursor
Hydrogel
Device
Flow
K. W. Bong et al., Langmuir, 31, (2015)
Functional Soft Nanomaterials Lab.

16. 1. Candidates materials for fat reduction 2. Fabrication of microgel
3. Method for adipocyte-specific binding
Functional Soft Nanomaterials Lab.

17. Modification adipocyte specific binding site
Adipocyte specific binding system
Functional Soft Nanomaterials Lab.

18. Thank you for your attention!