Thermogels.com
 

PolySciTech, Thermogelling Since 2009

Background

Thermogels are polymers that are liquid when refrigerated and solid when at room temperature. The polymer's steric hindrance combined with a low molecular weight prevents crystallization, and therefore creates thermosensitivity.

PolySciTech’s PolyVivo line offers these non-crystaline thermogel polymers in a wide variety of products. We are sure to have one just to your liking. PolyVivo polymers can be purchased at PolySciTech.com. If, however, you cannot find a thermogel for your needs, we do offer custom synthesis.

Why thermogel?

  • Micelle-type structure improves hydrophobic drug solubility and aids microparticle dispersion
  • In-vivo and in-vitro applications
  • Injectable
  • Degradable

Properties

  • Extremely sticky and viscous in its dry and natural state
  • Polymers thermogel in solution
  • For low molecular weight triblock copolymers (Gallery Items PolyVivo AK12 and AK24)
    • PEG1000 can be used to slightly lower the gelation temperature
    • NaSCN can be used to raise the gelation temperature
    • This tuning process is described more thoroughly in the following research paper: Shim et. al. 2002, “Poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly (D,L-lactic acid-co-glycolic acid) triblock copolymer and thermoreversible phase transition in water” (PDF)

Tuning Thermogelation to Body Temperature

White Paper: Thermogel Mixtures Impact on Rheology August 28, 2013

“Help! My thermogel will not dissolve!”

There are many different ways to dissolve a thermogel. Counter-intuitively these polymers dissolve best when cold. The two primary ways of dissolution are to either place the material with water in the refrigerator or to (faster method) stir/shake it while keeping it cold.

Shown at right is a simple apparatus for stirring the material while it is kept cold. For this place a styrofoam box (one shown is the same one we use to ship polymers) along with either ice or cold packs on a magnetic stir-plate and with a stir bar in the container stir while it is cold. This takes time. Be prepared days in advance of use date. For additional information see “Users Guide for Thermogelling” (PDF).

 

Thermogel Showcase

Starring PolyVivo AK12, AK24, and AK36

AK12

AK12

(PLGA-PEG-PLGA, 1500-1000-1500 1:1 LA:GA)
formula

In its dry and native state PolyVivo AK12 is a gelatinous form. Its solid density is 1.5 g/ml. When this polymer is dissolved in water or saline at roughly 20% w/v solution it will act as a thermoreverse gelator. Dissolves best at 4° C (refrigerator) temperature typically overnight or over a few days and then use for your purpose. When warmed the solution will gel. Gelation is optimal at room temperature (20°-25° C). The polymer tends to solidify at 37° C and after a short time will release the water and return to solid polymer.

Rheology Chart

AK12 Rheology Chart

See this PDF to better understand the thermogellation properties of AK12 in various solutions: “Thermo-Gelation Properties AK12 Batch 1 in Different Solution Conditions”

At 5° C the viscosity of AK24 in a 20% solution is 0.02271 Pa-s.

In-vivo surgical usage is as easy as 1, 2, 3:

  • Dissolve AK12 as a solution between 10-30% (w/v) in water or saline (20% is recommended)
  • Add your deliverable to the solution, mixing while cold to prevent gellation
  • Use within 2-3 weeks

Microparticle Delivery

The use of AK12 (an alternate to former Macromed's Regel) for delivery of microparticles has recently been published by Stanford University for its use as a thermogelling agent. “Drug Release from Electric-Field-Responsive Nanoparticles” (Ge, et. al. 2012), (PDF).

We describe a new temperature and electric field dual-stimulus responsive nanoparticle system for programmed drug delivery. Nanoparticles of a conducting polymer (polypyrrole) are loaded with therapeutic pharmaceuticals and are subcutaneously localized in vivo with the assistance of a temperature-sensitive hydrogel (PLGA-PEG-PLGA). We have shown that drug release from the conductive nanoparticles is controlled by the application of a weak, external DC electric field. This approach represents a novel interactive drug delivery system that can show an externally tailored release profile with an excellent spatial, temporal, and dosage control.

AK24

(PLGA-PEG-PLGA, 1500-1000-1500 3:1 LA:GA)
AK24

AK24 is silimar to AK12 except it has a slightly higher onset temperature for gelation (20° C as opposed to 15° C) and slower degradation due to higher lactide content.

Rheology Chart

AK24 Rheology chart
 

A common question regarding thermogels is how ‘fast’ do they gel upon warming. A large volume of thermogel solution is a relatively poor example because the ‘bottle-neck’ to gelation speed is how quickly the mass of water’s temperature can be increased in order to effect gelation. In the sense of an injectable depot, the cold-gel solution is forced through a fine-gauge needle into a warm body. This provides a relatively high surface area for heat transfer and, in this condition, the gel reaches body temperature more rapidly than a typical in-vitro type test such as placing a glass vial full of gel in an incubator as the incubator must slowly warm the vial itself and then the contents to 37 °C to achieve gelation. As can be seen in the video below, when spread out into a fine layer more representative of actual in-vivo conditions, the gel-speed is quite rapid happening in under a few seconds.


 

AK36

AK36

PolyVivo AK36 is an injectable thermogel with high-longevity in-vivo due to a slowly degrading polycaprolactone block. Dissolution of this material requires that it first be slurried into water at 4° C then dissolved at 80° C with stirring to break-down the PCL crystalline domains and subsequently chilled back to 4° C overnight to equilibrate. The resultant solution (20% w/v) has thermogellation properties suitable for solidification in the body. As shown, the room-temperature solution can be injected through even a 27 Ga needle.

Visit PolySciTech.com for a full listing of all PolySciTech Thermogels.

You can find John Garner's article Thermogelation of PLGA-block-PEG-block-PLGA Copolymers at the Sigma-Aldrich web site.

 

References

Drug Release from Electric-Field-Responsive Nanoparticles. Jun Ge, Evgenios Neofytou, Thomas J. Cahill, III, Ramin E. Beygui, and Richard N. Zare. ACS Nano 2012 6 (1), 227-233.

Myung Seob Shim, Hyung Tak Lee, Woo Sun Shim, Insun Park, Hyunjung Lee, Taihyun Chang,Sung Wan Kim, Doo Sung Lee “Poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly (D,L-lactic acid-co-glycolic acid) triblock copolymer and thermoreversible phase transition in water” J Biomed Mater Res 61: 188–196, 2002. (PDF)

 

Related Sites

 
Thermogels.com