U g e l s t a d L a b o r a t o r y

Nanomaterials for Drug Delivery

SulalitPhD StipendiatUgelstad Laboratory, Dept. of Chem. Eng., NTNU

18th November, 2013

2

Roadmap

Drug pathway

Golden rules

Developments on Layer by layer (LBL) approach

Developments on hydrogels

Future Work

3

E. Markovsky et al. / Journal of Controlled Release 161 (2012) 446–460

4

Monodisperse Nanoparticle (NP) population

Biocompatibility

Long circulation times

Target specific

Delivery of cargo

Golden Rules

5

LBL approach - outline

Ag

(a) (b)

Sodium citrate synthesis with reflux

Poly Lysine (PL) coating

Rat PGP siRNA and negative control siRNABBB

6

Na-citrate baseline

PL addition

siRNA addition

∆f

(Hz)

Time (s)

∆mPL = 8533 ng cm-2

∆msiRNA = 2854 ng cm-2

Sauerbrey equation:

QCM Results

7

LBL approach – preliminary results

(a) (b)

~38nm Ag NPs (DLS) , -45 mV

~66nm Ag-PL NPs (DLS) +33 mV

Ab

sorb

an

ce

Wavelength (nm)

(a) 427nm

(b) 432nm

- PGP siRNA- Ctrl siRNA

PGP silencing in vitro

8

- Monomer + cross linking agent in water

-T>LCST

-Homogeneous nucleation on collapsed oligomers

-Oligomer and monomer addition, aggregation

Low PDI, control of charge,size, cross-link density

Precipitation polymerization

Sythesizing PNIPAm

Re-crystallization

10

Size of PNIPAm at different concentrations

Size(nm)

Temperature (°C)

LCST

11

PNIPAm concentration of 14.73 mg/mL

Size(nm)

Temperature (°C)

LCST

12

Size of PNIPAm/AAc at different concentrations

Size(nm)

Temperature (°C)

VPTT

13

Optimization of Au-PNIPAM-PAAC hydrogels

PGP silencing studies

EM setup for release studies

Drug Release Kinetics

Shape effect in coating

The road ahead!

14