Polymer membrane and methods of manufacturing thereof

Abstract

This invention relates to a polymer membrane comprising a hydrogen bond donor polymer and a hydrogen bond acceptor polymer and to the use of such membrane as the shell of a capsule. The invention also relates to a method of manufacturing a polymer membrane comprising a step of contacting an aqueous phase comprising a first polymer, and an oil phase comprising a second different polymer; wherein one polymer is a hydrogen bond donor polymer and the other polymer is a hydrogen bond acceptor polymer. The invention also relates to a method of encapsulation comprising a step of manufacturing a polymer membrane.

Claims

1. A polymer membrane comprising a hydrogen bond donor polymer and a hydrogen bond acceptor polymer; wherein said hydrogen bond donor polymer is made of one or more monomers, and comprises: a hydrogen bond donor group comprising carboxyl in at least 75% of the monomer units relative to the total number of monomer units in the polymer; and a lateral substituent comprising at least one hydrophobic group selected from the group consisting of alkyl, cycloalkyl and aryl, in at least 75% of the monomer units relative to the total number of monomer units in the polymer; wherein said hydrogen bond acceptor polymer is made of one or more monomers, and comprises: a hydrogen bond acceptor group comprising ether or ester in at least 75% of the monomer units relative to the total number of monomer units in the polymer; and a lateral substituent comprising at least one hydrophobic group selected from the group consisting of alkyl, cycloalkyl and aryl in at least 75% of the monomer units relative to the total number of monomer units in the polymer; wherein said hydrogen bond acceptor polymer is selected from the group consisting of polypropylene oxide (PPO), poloxamers and polyvinyl acetate (PVAc)-polyvinyl alcohol (PVA) copolymers; wherein said polymer membrane does not comprise any charged polymer, wherein the hydrogen bond donor polymer and the hydrogen bond acceptor polymer are linked together by hydrogen bounds; and wherein the shear storage modulus G′ of said polymer membrane, measured at 1 rad/s, is at least 0.5 N/m.

2. The polymer membrane according to claim 1, wherein said hydrogen bond donor polymer is poly(methacrylic) acid.

3. The polymer membrane according to claim 1, wherein said hydrogen bond acceptor polymer is selected from the group consisting of polypropylene oxide and a poloxamers, wherein the poloxamer comprises an amount of polypropylene oxide monomer ranging from 50% to 100% in number of monomers relative to the total number of monomer units in the poloxamer.

4. A method of manufacturing a polymer membrane comprising contacting: an aqueous phase comprising a first polymer; and an oil phase comprising a second different polymer; wherein one of said first and second polymers is a hydrogen bond donor polymer and the other is a hydrogen bond acceptor polymer; wherein said hydrogen bond donor polymer and said hydrogen bond acceptor promoter are defined according to claim 1; and wherein both said first and second polymers are not charged polymers.

5. The method according to claim 4, wherein said hydrogen bond donor polymer is poly(methacrylic) acid.

6. The method according to claim 4, wherein said hydrogen bond acceptor polymer is selected from the group consisting of polypropylene oxide and poloxamers, wherein the poloxamer comprises an amount of polypropylene oxide monomer ranging from 50% to 100% in number of monomers relative to the total number of monomer units in the poloxamer.

7. The method according to claim 4, wherein both said first and second polymers assemble spontaneously by means of hydrogen bounds.

8. The method according to claim 4, wherein the shear storage modulus of the polymer membrane manufactured by said method, measured at 1 rad/s, is at least 0.5 N/m.

9. A capsule comprising a core and a shell around said core, wherein said shell comprises a polymer membrane according to claim 1.

10. A composition comprising a polymer membrane according to claim 1.

11. A composition comprising a dispersion of oil droplets in an aqueous phase, wherein each oil droplet is coated by a polymer membrane according to claim 1, wherein either the hydrogen bond donor polymer is present in the aqueous phase and the hydrogen bond acceptor polymer is present in the oil droplets, or the hydrogen bond donor polymer is present in the oil droplets and the hydrogen bond acceptor polymer is present in the aqueous phase.

12. A method of encapsulation comprising: forming around a core a polymer membrane according to claim 1.

13. A method of encapsulation comprising the method of manufacturing a polymer membrane according to claim 4.

14. A composition comprising capsules according to claim 9.

15. A method of encapsulation comprising: forming around a core a polymer membrane to manufacture a capsule according to claim 9.

16. The polymer membrane according to claim 1, wherein the shear storage modulus G′ of said polymer membrane, measured at 1 rad/s, is at least 1.0 N/m.

17. The polymer membrane according to claim 1, wherein the shear storage modulus G′ of said polymer membrane, measured at 1 rad/s, is at least 5.0 N/m.

18. The method according to claim 8, wherein the shear storage modulus of the polymer membrane manufactured by said method, measured at 1 rad/s, is at least 1.0 N/m.

19. The method according to claim 8, wherein the shear storage modulus of the polymer membrane manufactured by said method, measured at 1 rad/s, is at least 5.0 N/m.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 is a graph showing the evolution of the thickness (h) of a polymeric membrane according to the invention over time (t) as discussed in Example 2, measured by two methods: in situ spectrometry (empty circles) and ex situ profilometry (filled circles). Error bars are shown when larger than markers size.

(2) FIG. 2 is a combination of pictures and sketches illustrating the formation of wrinkles upon gentle pressure (3-a), the removal by a plate (3-b) and the subsequent restoration (3-c) of a polymeric membrane according to the invention, as disclosed in Example 2.

(3) FIG. 3 is a graph showing the evolution of the interfacial storage modulus G′.sub.s (filled circles) and of the interfacial loss modulus G″.sub.s (empty circles) of a polymeric membrane according to the invention as a function of strain, which evidence that it can self-repair after being damaged, as disclosed in Example 2. Frequency is 1 rad.Math.s.sup.−1.

(4) FIG. 4 is a combination of pictures and sketches showing centimeter-sized capsules formed by dripping of droplets (4-a), the formation of capsules with a diameter of 25 μm±10 μm using a rotor-stator homogenizer (4-b), and formation of monodisperse population of micron-sized capsules by using a microfluidic chip (4-c), as disclosed in Example 3.

EXAMPLES

(5) The present invention is further illustrated by the following examples.

Example 1: Polymers for Manufacturing a Polymeric Membrane

(6) Hereafter are provided examples of hydrogen bond donor and hydrogen bond acceptor polymers susceptible to be combined to create a polymeric membrane according to the invention.

(7) TABLE-US-00001 TABLE 1 Hydrogen bond donor Hydrogen bond acceptor # polymer polymer 1 PMAA PPO 2 PMAA PVA-PVAc 25%-75% 3 PMAA PPO-PEO (L61, L81, L101, L121, 17R4 or 31R4) 4 PEAA PPO-PEO (L44, L64, P84, P104, P65, P75, P85 or P105) 5 PSMA PPO 6 PSMA PVA-PVAc 25%-75% 7 PSMA PPO-PEO (L61, L81, L101, L121, 17R4 or 31R4) 8 PVA-PVAc 75%-25% PPO 9 PVA-PVAc 75%-25% PVA-PVAc 25%-75% 10 PVA-PVAc 75%-25% PPO-PEO (L61, L81, L101, L121, 17R4 or 31R4) 11 PMAA PDMAEMA

(8) Hereafter are provided the hydrogen bond donor and hydrogen bond acceptor polymers previously listed, classified according to their hydrophilic character (more water-soluble than oil-soluble) or their hydrophilic character (more oil-soluble than water-soluble).

(9) TABLE-US-00002 TABLE 2 Hydrophilic polymer Type poly(methacrylic) acid (PMAA) H bond donor styrene-maleic acid copolymer (PSMA) H bond donor Poly(vinyl) alcohol (PVA) - Poly(vinyl) acetate H bond donor (PVAc) 75%-25% polypropylene oxide (PPO)-polyethylene oxide (PEO) H bond acceptor copolymer selected from: L44, L64, P84, P104, P65, P75, P85 and P105

(10) TABLE-US-00003 TABLE 3 Lipophilic polymer Type poly(ethylacrylic) acid (PEAA) H bond donor polypropylene oxide (PPO) H bond acceptor polypropylene oxide (PPO)-polyethylene oxide (PEO) H bond acceptor copolymer selected from: L61, L81, L101, L121, 17R4 and 31R4 Poly(vinyl) alcohol (PVA) - Poly(vinyl) acetate H bond acceptor (PVAc) 25%-75% poly(dimethylaminoethyl methacrylate) (PDMAEMA) H bond acceptor

(11) Examples of embodiments of the manufacturing method of the invention consists in contacting at a water-oil interface one hydrophilic polymer from Table 2 solubilized in an aqueous medium and one lipophilic polymer from Table 3 solubilized in an oil medium, to obtain a polymer membrane according to the invention.

Example 2: Polymer Membrane and Manufacture Thereof

(12) Hereafter is detailed the manufacture of a polymer membrane according to the invention comprising poly(methacrylic acid) (PMAA) as hydrogen bond donor polymer and poly(propylene oxide) (PPO) as hydrogen bond acceptor polymer.

(13) Materials and Methods

(14) Water-based solution is prepared by dissolution of 1 wt % of PMAA (molar mass: 100 000 g/mol) (Poly-sciences, Inc.) in water-distilled and purified with milli-Q apparatus (Millipore). Molar mass of a repeat unit MAA is 87:1 g/mol, which corresponds to a molar concentration of 0:11 mol/L. pH is adjusted at 3 by adding hydrochloric acid (HCl) (Sigma-Aldrich) solution concentrated at 1 M or sodium hydroxide solution (NaOH) (Sigma-Aldrich) solution at the same concentration and measured with pH-meter pHM 250 ion analyser Meterlab (Radiometer Copenhagen) with a precision of 0.05 pH.

(15) Oil-based solution is prepared by dissolution of 1 wt % (weight by weight) of PPO (molar mass: 4000 g/mol) (Sigma-Aldrich) in isopropyl myristate (Sigma-Aldrich) or in Miglyol 812N (IMCD France/Sasol). Miglyol is a neutral oil consisting of caprylic/capric triglyceride (C.sub.8/C.sub.10 chains). Molar mass of a repeat unit PO is 58:1 g/mol, which corresponds to a molar concentration of 0:15 mol/L. We choose 1 wt % for both polymers to ensure an excess of polymer in bulk phases with respect to the interface, while being in dilute regime (<3 wt %) to have a low viscosity solution, hence a better sensitivity to interfacial rheology measurements.

(16) To manufacture the polymer membrane, the aqueous phase is put into contact with the oil phase.

(17) Membrane thickness is measured in situ with an optical spectrometer V8E (Specim) assembled on an optical microscope (Olympus). The focus is set strictly at the interface where the membrane grows. Thickness is also measured ex situ with an optical profilometer Microsurf 3D (Fogale nanotech) by transferring the membrane from the liquid to a glass slide.

(18) To probe interfacial rheometry, an AR-G2 rheometer (TA Instruments) is used with a Double-Wall-Ring geometry. Torque measurement resolution is 1 nN/m. The ring-shaped container is half-filled with approximatively 21 mL of water solution until obtaining a flat interface pinned horizontally between the walls' edges, so the meniscus deformation can be neglected. Then, the ring is carefully approached to the interface and precisely placed to keep a flat interface between the wall corner and the diamond-shaped corner of the ring. Finally, the rest of the container is slowly filled with the same volume of oil. Measurements are controlled by TRIOS software (TA Instruments). A strain rate of 0.1% is imposed to ensure that the measurements are all carried out in the linear regime.

(19) Results

(20) The membrane assembly was probed in a model plane geometry. To prepare a flat polymer membrane, the aqueous phase containing the hydrogen bond-donor polymer (PMAA) was put into contact with the oil phase containing the hydrogen bond-acceptor polymer (PPO).

(21) The thickness of the membrane was measured either in situ using an optical spectroscope, or ex situ using an optical profilometer to analyze the membrane deposited from the liquid onto a glass slide.

(22) The membrane grows continuously with time without reaching any saturation over months and its thickness is 10 μm after 100 days as shown in FIG. 1. The thickness, which scales as t.sup.1/2, suggests a diffusion-limited mechanism. The associated diffusion coefficient has been determined from the extrapolated intercept of the long-time regime in FIG. 1. The obtained value was of the order of 10.sup.17 m.sup.2/s, which is much lower than the diffusion coefficient of the polymers in the bulk phases. This suggests that the growth of the membrane was controlled by the diffusion of the polymer molecules through the membrane to complex with their hydrogen-bond partner.

(23) This model geometry further allows probing the self-healing properties of the flat membrane as shown in FIG. 2. The presence of the membrane at the oil-water interface was revealed by the formation of wrinkles as a gentle strain was applied with a spatula (FIG. 2-a). Using a microscope cover slide, the initial polymer membrane was pushed on the side, which allowed a fresh one to appear (FIG. 2-b). A few seconds later, wrinkles could be seen at the oil-water interface as the membrane was gently pressed with a spatula again (FIG. 2-c). This simple test showed that the membrane reassembled quickly from the oil and water reservoirs of polymer molecules.

(24) A double-wall-ring interfacial shear rheometer was used to measure the surface shear storage and loss moduli of the membrane, G′.sub.s and G″.sub.s, respectively, with increasing deformation amplitudes from 0.1% to 100%. At deformation amplitude of 0.1%, the surface shear storage modulus was about 10 N/m (FIG. 3). Above a critical strain, which is about 0.5%, the system was no longer in the linear regime and both moduli drop by several orders of magnitude (FIG. 3). A visual inspection of the interface indicated that the membrane is damaged. However, when the deformation was decreased again, the initial values of the moduli were recovered in about an hour. These results suggested that the membrane easily rearranged through diffusion of the polymer molecules towards and inside the membrane, owing to the hydrogen bond non-covalent interactions.

(25) These results evidence that a polymer membrane can be formed at the interface of a water-oil system by contacting a hydrogen bond-donor polymer included in an aqueous phase with a hydrogen bond-acceptor polymer included in the oil phase.

Comparative Example 2: Polymer Membrane According to WO2014/064255

(26) A comparative polymer membrane of 5 layers of PMAA and PVP has been made according to example 1 of WO2014/064225.

(27) The surface shear storage modulus G′ of the obtained global layer has been measured as in example 2 above.

(28) The value was about 0.2 N/m at 1 rad/s.

Example 3: Capsules and Manufacture Thereof

(29) Hereafter is described the assembly around oil droplets of the polymer membrane of Example 2, for encapsulation purposes.

(30) Material and Methods

(31) Emulsions have been prepared in vials by gently pouring 6 mL of water-based solution and then 4 mL of oil-based solution as described in Example 2. An Ultra-Turrax disperser (IKA) was used to form an emulsion with a speed of 20000 rpm during 30 seconds.

(32) The microfluidic device was first designed with a dedicated software (Clewin) and printed on a mask. Then a SU-8 negative photoresist resin (Micro Chem) was spin-coated with the desired thickness on a silicon wafer. Two-layer lithography were used with no intermediate step (Leman, M. et al., Lab on a Chip, Vol. 15, 2015, pp. 753-765). The obtained silica mold was filled with PDMS (poly(dimethylsiloxane)) (Sylgard 184, Dow Corning) mixed with 10% (w/w) curing agent and incubated at 70° C. for about 4 hours. The PDMS was peeled off the mold and the entrances and exits were punched with a 0.5 mm-diameter Harris Uni-Core biopsy punch (Electron Microscopy Sciences). The PDMS was finally sealed to a glass slide with a PDC-002 oxygen plasma cleaner (Harrick Plasma). Every entrance or exit of the chip was connected through PEEK (poly(etheretherketone)) tubings to a small vial. Applied pressures in vials (about 400 mbar) were controlled by a MFCS pump (Fluigent).

(33) Results

(34) First, centimeter-sized capsules have been produced by gently dripping oil drops containing PPO into a water phase containing PMAA (FIG. 4-a).

(35) Secondly, using a rotor-stator homogenizer and by shearing the two fluid phases containing the polymers, capsules with a diameter of 25 μm±10 μm (FIG. 4-b) have been manufactured. This one-step process enables the preparation of microcapsules that are stable for months.

(36) Thirdly, microfluidics was used to produce a monodisperse population of micron-sized capsules. The microfluidic chip was composed of a flow-focusing unit where oil droplets containing PPO were produced in a pure aqueous phase to avoid fast interfacial complexation at the constriction, which may plug the flow-focusing unit. The PMAA solution was then added right after to trigger the interfacial complexation at the oil-water interface. The capsules were finally collected in a chamber with a filter made by two-layer lithography, where they can be stored during several days (FIG. 4-c). This semi-permeable filter being permeable to the external aqueous phase but not to capsules, allows to increase the capsule concentration.

(37) Even in close contact to each other, all capsules presented a unique stability compared to standard surfactant-stabilized emulsions and no coalescence was observed. It is especially the case for the centimeter-sized droplets which are known to be very difficult to stabilize, as the coalescence probability increases with the droplet size. Without being linked to any theory, the Applicant believes that the high interfacial rigidity of the polymer membranes protects the assembly against coalescence.

(38) Interestingly, when increasing the pH from 3 to 6, it was observed that the shell of the capsule progressively dissolves, so that at a pH value of 5.5, the oil core of the capsule is released from the capsule. This property will advantageous when designing capsules wherein the core is intended to be released in acidic conditions.