BIOMATERIALS LAB Drug Delivery & Controlled Release

Monday, March 19th and Tuesday, March 20th

BME 245/445 – Lab 4

PRE-LAB Sign-in Quiz (Lin. 2009)

BME 245/445 – Lab 4

Big Picture: Drug Delivery

Control drug delivery rate, dose & location

BME 245/445 – Lab 4

Toxic Level

With DeliveryDevice

Time

Dru

g C

on

cen

trat

ion

Period of Efficacy

 

TraditionalDelivery

Therapeutic Range

Big Picture: Drug Delivery

Monolithic Device Drug is released by diffusion out of polymer matrix Release rate depends on:

Drug loading Drug size Mesh size Shape of device

Applied in Norplant – implantable contraceptive device Release hormone over 5 years Discontinued – unpopular, not cost-effective

BME 245/445 – Lab 4

http://www.sigmaaldrich.com/materials-science/biomaterials/tutorial.html

LINEAR MOLECULES

PEGMA (2, 10, 20kD) Increase number of repeat units (n) Alter mesh size and thus rate of BSA release

Small Mesh Size Large Mesh Size

BME 245/445 – Lab 4

METHACRYLATE POLYMERIZATION

1 “Arm”

(Lin, C.C., Pharmaceutical Research. 26(3): 631-643. 2009)

Step-growth Polymerization

PEG MA

BME 245/445 – Lab 4

SECTION 1

PEGMA Network Synthesis

1. 10wt% PEGDA in PBS+BSA (10 mg/mL)

2. 10% photo-initiator by volume (LAP)

3. 40μL placed in 1mL syringe (tip cut off) to create cylindrical hydrogel sample geometry

4. exposed to UV-lamp for 10min

5. Remove and place in PBS

PEG (mg) PBS solution (μl) Initiator (μl)28.3 225 25

SECTION 2

Protein Collection Time Course (done by TA)

BSA in hydrogel will release into surrounding PBS PBS will be routinely changed (stored in -80°C freezer) BSA concentration will be assessed for total release

BME 245/445 – Lab 4

SECTION 3

Protein Detection Assay – Coomassie

Compared unknowns to known [BSA] standards Measure Absorbance at 590nm

BME 245/445 – Lab 4

From plate reader….

BME 245/445 – Lab 4

Absorbance at 590 nm  PEG MW

Sample #

2 kDa 10 kDa 20 kDa

1      

2      

…      

n      

What we are interested in….%

BS

A r

elea

sed

Time

BME 245/445 – Lab 4

Theoretical Governing Eqns

BME 245/445 – Lab 4

z=0

z=L

z=L/2

Drug diffuses out

 

Drug diffuses out

Governing Eqns

BME 245/445 – Lab 4

z=0

time

z=L

Dru

g C

on

cen

trat

ion

CA

C0

0

Simplifying Governing Eqns

BME 245/445 – Lab 4

Mesh Size Calculations

BME 245/445 – Lab 4

Safety

General PEG/PBS/BSA are relatively benign Lab glasses, gloves, closed toed shoes No food, no drinks, no applying makeup

LAB TEAMS- Monday

TEAM A2k

TEAM B2k

TEAM C10k

TEAM D10k

TEAM E20k

Ripa Chowdhury

Chris Farrar Matt Hazelett Caressa Chen Ruth Davis

Eric Comeau Christine Mclin Rachel Rakvica Tonima Quabili Corinne Lampe

Margaret Fettis Kristen Harding

Yi Rao Ka Lai Tsang Mitchell Long

Bingqing Wang Andrea Wong Stephen Zhang Chris Schmitt

BME 245/445 – Lab 4

LAB TEAMS- Tuesday

TEAM F2k

TEAM G10k

TEAM H20k

Team I20k

Ibrahima Bah Raymond Goo

Seung Hoon Lee Alex Kotelsky

Joseph Mozingo

Sara Nowacki David Narrow Jennifer Williams

Carly Sombric

Spencer Putnam

Erin Schnellinger

Yoon-Suk Yi

Nicole Varble Shijie Zhong Sean Rodriguges Sijia Zhang

Douglas Clift Robert Mcwhorter

Shijie Zhong

BME 245/445 – Lab 4