Difference between revisions of "Team:TU Darmstadt/Project/PLGA"

PLGA

Abstract

In order to produce plastics, there are many different ways of polymerization. Given that our polymer is a polyester, there are two possibilities of polymerization. The first one is a polycondensation directly out of the monomers lactic- and glycolic acid by eliminating water molecules. A problem of this method is, that the resulting polymer has lower molecular weights, which diminish the mechanical characteristics. Another possibility is to use an anionic ring opening polymerization. However, it is necessary to dimerize the monomers before using them for such a polymerization, otherwise an anionic ring opening polymerization would not work. The reason why we chose an anionic ring opening polymerization for our project is the fact that such a polymerization causes high molecular weights and is controllable by the amount of initiator used in the set up. The manufactured polymers are than analyzed by gel permeation chromatography (GPC) to determine their molecule weight. Polymers with a sufficient enough weight are than used to manufacture nanospheres.

Introduction

Like many other common plastics like Polycarbonate (PC) or Polyethylenterephthalate (PET), PLGA (poly-lactid-co-glycolid) belongs to the family of polyesters. PLGA is build from lactid acid and glycolic acid monomers and is characterized through both a high mechanical resistance and being a thermoplastic

Synthesis of PLGA

Two set ups of PLGA were processed during our time in the laboratory through an anionic ring-opening polymerization. For that the monomers are put in a water free reaction vessel, melted and reacted with the initiators. The method is described in the method book.

PLGA (I) with a ratio lactide/glycolide of 75/25

and

PLGA (II) with a ratio lactide/glycolide of 67/33

Results and Discussion

Analysis through GPC

The PLGA (I) set up from 30.07.2018 (Ratio 75/25)

Hier kommt der GPC Graph hin

3 mg of the product were solved in 1 ml of the THF/toluene-buffer and measured with a GPC against a polystyrene standard sample. The result shows an average molecule weight of 23,695 g/mol. The expected molecule weight is determined to be 361,669 g/mol. The difference between the expected and the measured result can be explained by the magnetic stirring, which was not able to stir the reaction mixture sufficiently at higher viscosity. Through that the longer polymer chains with a higher density descended, and the lighter monomers with a lower density ascended inside the vessel. This left the polymer chains no possibility to attach the remaining monomers it their ends, while the reaction mixture grew cold and solidified.

The PLGA (II) set up from 24.08.2018 (Ratio 67/33)

Hier kommt auch ein GPC Graph hin

3 mg of the product were solved in 1 ml of the THF/toluene-buffer and measured with a GPC against a polystyrene standard sample. The result shows an average molecule weight of 167.9*10^6 g/mol. The expected result is determined to be 2.106*10^6 g/mol. The difference between the expected and the measured result can be explained by humidity, which deactivated part of the Initiator molecules, prohibiting the start of a chain. So the monomers had the chance to spread to other chains and get attached to them, what increased the length of those chains.

NRM-Results

After the polymer was purified and dried, the yield of the synthesis was determined.

Formel!!!

The maximal possible yield is approximately equal to the total mass of monomers: Table 1: used amount of monomers plus the yields of the synthesis (total and relative).

As the yields in table one shows, the relative yields are between[....]%. The yields are small. That is caused that we have not the right equipment to guaranty a homogeny melt. Thus with the progress of the synthesis, the viscosity of the melt becomes higher. During the synthesis the magnetic stirring becomes weaker. After a certain time, the stirring stops. At this moment we stop the reaction to have results we can compare. The time the reaction needs depends on the amount of monomers and the ratio of monomers to co-initiator. It would be necessary to use mechanical stirring to guaranty a homogeny melt to a conversion of 100%.

NMR-Spectroscopy: To analyze the ratios inside our PLGA co-polymer we used 1H NMR-spectroscopy. We normalized the CH-group of lactide to 1. In this way we could determine the ratio of the monomers about equation 2:

Formel!!!

To calculate the ratios, it is important to use the CH3-group of lactide and not the normalized Ch-group. This equations is valid for all monomer ratios. Table 2: monomer ratio of PLGA polymers determined by NMR-spectroscopy.

To determine the composition it is necessary to assign the peaks belonging to a specific proton group of a monomer. The figure 1 shows the structure of PLGA and its belonging NMR-spectra. The obtained areas of the peaks are typical for the PLGA co-polymer. The used peaks are the methyl protons of lactide with a shift of δ=1.44-1.69 plus the glycolide protons with a shift of δ=4.69-4.93 and the α methylene protons at a shift of 3.66-3.73.

Spectra!!!

Aus den NMR-Spektren geht hervor, dass das Verhältnis der Monomere im synthetisierten Polymer nicht den eingesetzten Verhältnissen entsprechen [Tab. 3]. Die Menge an eingebautem Glycolid ist höher. Damit bestätigen die Ergebnisse, dass Glycolid deutlich reaktiver ist als Lactid.

Table 3: theoretische und erhaltene Verhältnisse im Vergleich

Ist das anfänglich Verhältnis an Glycolid höher wirkt sich das deutlich auf das Verhältnis im Polymer aus. Wird die Menge an eingesetztem Glycolid von 25- auf 33% erhöht, dreht sich das resultierende Verhältnis (L/G) von 60/40 zu 40/60. Um trotz dieser unterschiedlichen Reaktivitäten die resultierenden Verhältnisse vorhersagen zu können, probieren wir anhand der Ergebnisse Geschwindigkeitskonstanten für das Einbauen eines der Monomere zu bestimmen. Mit Hilfe dieser soll anschließend ein kinetisches Modell erstellt werden, dass je nach eingesetztem Monomerverhältnis das entstehende Verhältnis im Polymer berechnet. Außerdem kann mit Hilfe des kinetischen Modells die Wahrscheinlichkeit von Glycolidblöcken bestimmt werden. Diese führen bei einer Synthese mit einem Ausgangsverhätnis von 1:1 zu einer veränderung der Löslichkeit. Das PLGA verändert das Löslichkeitsverhalten.(Weiter Infos zum modellieren finden Sie hier)