Facile preparation of swellable microgels using spray drying

Abstract

The present invention provides a hydrogel comprising a crosslinked polymer formed by reaction of one or more polymers and a polycarbodiimide, wherein the one or more polymers are selected from polymers that contain one or more carboxylic acid, hydroxyl, amino and thiol functional groups. The present invention also provides method of manufacturing a hydrogel as disclosed hereinbefore, the method comprising the steps of: (a) providing a precursor solution comprising a solvent, one or more polymers, and a polycarbodiimide; and (b) subjecting the precursor solution to spray drying and collecting the resulting hydrogel, wherein the precursor solution has a pH that is less than or equal to 6.

Description

[0001] FACILE PREPARATION OF SWELLABLE MICROGELS USING SPRAY DRYING

[0002] FILED OF INVENTION

[0003] The present invention generally relates to hydrogels, and more particularly relates to swellable microgels and their preparation methods.

[0004] BACKGROUND

[0005] The listing or discussion of a prior-published document in this specification should not necessarily be taken as an acknowledgement that the document is part of the state of the art or is common general knowledge.

[0006] Microgels are micron-sized crosslinked polymer that are effective colloidal stabilizers, have a high surface area, and have a superior swelling potential. These properties make microgels applicable as controlled release agents, adsorbents, and emulsifiers. In agriculture, microgels can used as a soil amendment to enhance water retention properties, improve irrigation efficiency and promote nutrient retention in the soil. In soil, microgels strongly adheres to soil particles and functions as micron-sized water reservoirs. Treating soil with microgels has be shown to reduce the vulnerability of crops to water stress and reduce irrigation run-off / seepage thus maximizing water usage.

[0007] Currently, emulsification, precipitation, extrusion, and spray-assisted techniques are used to prepare polymer microspheres or microgels. The selection of the appropriate technique primarily depends on the properties of the raw material and the intended application of the product. It is often better to use extrusion or emulsification techniques when microparticles with a narrow size distribution is desired. However, microgel production using extrusion and emulsification techniques is low yield and typically uses harmful organic solvents (e.g., chloroform, toluene, benzene, DMSO). For industrial applications, spray-assisted techniques such as spray drying are preferred due to their simplicity and scalability. Crosslinked polymeric microspheres or microgels can be prepared using spray drying either by simultaneously spraying the crosslinker with the polymer solution or premixing the crosslinker with the polymer solution. High production yield can be achieved by pilot scale (10-30 L / h) and industrial scale (>30 L / h) spray dryers.

[0008] Crosslinking techniques used to fabricate hydrogels and microgels often use reactive and volatile crosslinkers. However, these volatile crosslinkers typically exhibit low crosslinking efficiency at the elevated temperatures used in spray drying processes (> 120 °C). For example, epichlorohydrin used to crosslink hydroxyl-containing polymers to prepare microgels for various applications has a boiling point of 118 °C. When spray drying polymer mixtures at 120 °C, excess epichlorohydrin must be added to compensate for volatilization, making the process inefficient and ultimately unsuitable for this application. Alternatively, many conventional crosslinkers such as glutaraldehyde, 1 ,4-butanediol diglycidyl ether (BDDE), and divinyl sulfone are potentially carcinogenic or toxic, posing significant health hazards when volatilized at high volumes.

[0009] A safer alternative to reactive crosslinkers are Ca2+-crosslinked alginate microstructures (CLAMs). CLAMs are usually prepared by 1 ) adding alginate into the polymer mixture, 2) simultaneously spraying alginate-containing polymer mixture and dilute Ca2+solution through a three-liquid nozzle (e.g., 10-50 mM), and 3) drying the droplets at > 140 °C. Unfortunately, crosslinking via alginate (polyguluronate)-Ca2+complexation is susceptible to leaching in the presence of electrolytes (e.g., Na+, Mg2+, Fe3+) and at acidic conditions pH < 4.5. Ca2+leaching can cause the alginate-polymer structure to unravel which leads to the mechanical instability of the product (Escayo et al., ACS Appl. Polym. Mater. 2024, 6(10), 5833-5843).

[0010] Therefore, there exists a need for new microgels and preparation methods to address toxicity and mechanical instability issues associated with conventional crosslinkers used to prepare polymer microgels.

[0011] SUMMARY OF INVENTION

[0012] Aspects and embodiments of the invention are provided in the following numbered clauses.

[0013] 1. A hydrogel comprising a crosslinked polymer formed by reaction of one or more polymers and a polycarbodiimide, wherein: the one or more polymers are selected from polymers that contain one or more carboxylic acid, hydroxyl, amino and thiol functional groups.

[0014] 2. The hydrogel according to clause 1 , wherein the one or more polymers and the polycarbodiimide have a boiling point of greater than or equal to 220 °C.

[0015] 3. The hydrogel according to clause 1 or clause 2, wherein the one or more polymers are selected from the group consisting of a starch, cellulose, hydroxyethyl cellulose, methyl cellulose, ethylhydroxyethyl cellulose, and more particularly, carboxymethylcellulose (CMC), chitosan, alginate, pectin, agar, polyacrylic acid, polyacrylamide, polylactic acid, and polyvinyl alcohol.

[0016] 4. The hydrogel according to any one of the preceding clauses, wherein the polycarbodiimide is a polyethylene glycol-terminated polycarbodiimide.

[0017] 5. The hydrogel according to clause 4, wherein the polyethylene glycol-terminated polycarbodiimide is selected from one or both of:

[0018] (i)

[0019] , optionally wherein the number average molecular weight is of from 2,200 to 28,000 Daltons; and

[0020] , optionally wherein the number average molecular weight is of from 1 ,000 to 2,000 Daltons.

[0021] 6. The hydrogel according to clause 5, wherein the polyethylene glycol-terminated polycarbodiimide of clause 5(i) has a molecular weight selected: from 2,200 to 2,300 Daltons, from 3,700 to 3,900 Daltons, from 2,700 to 28,000 Daltons.

[0022] 7. The hydrogel according to any one of clauses 4 to 6, wherein the polyethylene glycol- terminated polycarbodiimide has a polyethylene glycol capping group having a number average molecular weight of from 100 to 500 Daltons on each end of the polycarbodiimide, such as from 200 to 400 Daltons, optionally wherein the polyethylene glycol capping group is a polyethyleneglycol methyl ether (MPRG).

[0023] 8. The hydrogel according to any one of the preceding clauses, wherein the hydrogel is in the form of microgel particles. 9. The hydrogel according to clause 8, wherein the particles of microgel have an average particle size of from 0.1 to 200 pm, such as from 0.2 to 100 pm, such as from 0.3 to 50 pm, such as from 0.5 to 3 pm, such as from 1 to 2 pm, as calculated using images of particles obtained at from 1 ,000 to 5,000 magnification using a scanning electron microscope.

[0024] 10. The hydrogel according to any one of the preceding clauses wherein one or more of the following apply:

[0025] (ai) a weight percentage attributable to the polycarbodiimide in the hydrogel relative to the total weight attributable to the one or more polymers in the hydrogel is from 0.05 to 10 wt%, such as from 0.1 to 5 wt%;

[0026] (aii) a swelling ratio (average diameter in water relative to average dry diameter) of from 350 to 2,000, such as from 400 to 1 ,738; and

[0027] (aiii) a x value of from 10 to 40%, such as from 1 1 to 30%.

[0028] 11. An agricultural formulation comprising a hydrogel according to any one of clauses 1 to 10.

[0029] 12. Use of a hydrogel according to any one of clauses 1 to 10 in crop cultivation.

[0030] 13. A method of agriculture comprising the steps of:

[0031] (bi) providing a formulation comprising a hydrogel according to any one of clauses 1 to 10; (bii) applying the hydrogel to a growing medium that comprises a seed or a plant and growing the seed or plant to provide a desired crop product.

[0032] 14. A method of manufacturing a hydrogel according to any one of clauses 1 to 10, the method comprising the steps of:

[0033] (a) providing a precursor solution comprising a solvent, one or more polymers, and a polycarbodiimide; and

[0034] (b) subjecting the precursor solution to spray drying and collecting the resulting hydrogel, wherein the precursor solution has a pH that is less than or equal to 6.

[0035] 15. The method according to clause 14, wherein the one or more polymers and the polycarbodiimide have a boiling point of greater than or equal to 220 °C.

[0036] 16. The method according to clause 14 or clause 15, wherein the one or more polymers are selected from the group consisting of a starch, cellulose, hydroxyethyl cellulose, methyl cellulose, ethylhydroxyethyl cellulose, and more particularly, carboxymethylcellulose (CMC), chitosan, alginate, pectin, agar, polyacrylic acid, polyacrylamide, polylactic acid, and polyvinyl alcohol.

[0037] 17. The method according to any one of clauses 14 to 16, wherein the polycarbodiimide is a polyethylene glycol-terminated polycarbodiimide, optionally wherein the polyethylene glycol capping group is a polyethyleneglycol methyl ether (MPRG).

[0038] 18. The method according to clause 17, wherein the polyethylene glycol-terminated polycarbodiimide is selected from one or both of:

[0039] (i)

[0040] , optionally wherein the number average molecular weight is of from 2,200 to 28,000 Daltons; and

[0041] , optionally wherein the number average molecular weight is of from 1 ,000 to 2,000 Daltons.

[0042] 19. The method according to clause 18, wherein the polyethylene glycol-terminated polycarbodiimide of clause 5(i) has a molecular weight selected: from 2,200 to 2,300 Daltons, from 3,700 to 3,900 Daltons, from 2,700 to 28,000 Daltons.

[0043] 20. The method according to any one of clauses 14 to 19, wherein the polyethylene glycol- terminated polycarbodiimide has a polyethylene glycol capping group having a number average molecular weight of from 100 to 500 Daltons on each end of the polycarbodiimide, such as from 200 to 400 Daltons.

[0044] 21 . The method according to any one of clauses 14 to 20, wherein the hydrogel is collected in the form of microgel particles. 22. The method according to any one of clauses 14 to 21 , wherein one or more of the following apply:

[0045] (ci) the one or more polymers are provided in an amount of from 1 to 20 % w / v, such as from 1 .5 to 7 % w / v, such as from 2 to 5 % w / v, such as about 3 % w / v in the precursor solution; (cii) the polycarbodiimide is provided in an amount of from 0.05 to 10 % w / v, such as from 0.1 to 5 % w / v in the precursor solution;

[0046] (ciii) the weight percentage of the polycarbodiimide relative to the weight of the one or more polymers if from 0.05 to 10 wt%, such as from 0.1 to 5 wt%;

[0047] (civ) a viscosity of the precursor solution is lower than the tolerance of a spray dryer model used in the preparation, for example the viscosity of the precursor solution is from 400 to 2,000 cP at 25 °C, such as from 500 to 1,200 cP at 25 °C, such as from 800 to 900 cP at 25 °C;

[0048] (cv) the precursor solution has a pH of greater than 4 and less than or equal to 6, such as from 5 to 6

[0049] (cvi) a temperature of from 100 to 200 °C for a spray drying collection chamber, such as from 120 to 180 °C;

[0050] (cvii) a nozzle diameter for the spray dryer of from 0.1 to 5 mm, such as from 0.15 to 2.5 mm, such as from 0.2 to 1 .5 mm, such as from 0.5 to 1 .0 mm, such as about 0.7 mm.

[0051] 23. The method according to any one of clauses 14 to 22, wherein the precursor solution is obtained by the steps of:

[0052] (aa) providing a pH adjusted solution of one or more polymers, where the pH of the solution is less than or equal to 6; and

[0053] (ab) adding the polycarbodiimide to the pH adjusted solution.

[0054] DRAWINGS

[0055] FIG. 1 depicts a) reaction scheme illustrating the preparation of polyethylene glycol terminated polycarbodiimide (PCD). (Note: MPEG: polyethylene glycol monomethyl ether, MPPO: 3- methyl-1-phenyl-2-phospholene-1 -oxide), b) structure of polyethylene glycol terminated polycarbodiimide derived from methylene bis(cyclohexyl) diisocyanate.

[0056] FIG. 2 depicts a) scanning electron microscopy (SEM) image of spray dried microgel at x5000 magnification, and b) optical micrograph of microgel dispersed in deionized water with particle size distribution derived from laser diffraction scattering.

[0057] FIG. 3 depicts a) reference Fourier transform infrared spectroscopy (FTIR) spectra of PCD 1 and CMC, and b) FTIR spectra of PCD-CMC mixture at pH 8.0, 7.0, 6.0, 5.0, and 4.0. FIG. 4 depicts spray dried PCD-CMC microgel at pH a) 7.0, b) 6.0, and c) 5.0.

[0058] FIG. 5 depicts SEM micrographs (x5000) of spray dried PCD-CMC microgel at a) 120 °C, b) 140 °C, c) 160 °C, and d) 180 °C.

[0059] FIG. 6 depicts optical micrographs (x60) of spray dried PCD-CMC mixture at a) 120 °C, b) 140 °C, c) 160 °C, and d) 180 °C. The number-weighed and volume-weighed particle size distribution of each sample shows polydispersity and particle aggregation in deionized H2O.

[0060] FIG. 7 depicts optical micrographs (x60) of spray dried PCD-CMC mixture containing a) 0.1%, b) 0.25%, c) 0.5%, d) 1.0%, e) 2.5%, and f) 5% PCD 1. The number-weighed and volume- weighed particle size distribution of each sample shows polydispersity and particle aggregation in deionized H2O.

[0061] FIG. 8 depicts a) x and swelling ratio values of PCD-CMC microgel prepared using varying PCD1 content in deionized water. The maximum swelling ratio was achieved for microgel with X value of 11% but was mechanically unstable, b) Swelling ratio values of PCD-CMC microgel dispersed in pH 2.0-10.0 buffer solution. The electron-withdrawing ureide linkage may have lowered the pKa value for -COOH.

[0062] FIG. 9 depicts dsof PCD-CMC microgel in 0-75 mM NaCI, MgCh, and CaCh electrolyte solutions. The reduction of the dsdue to the charge screening effect is < 10%. The result also indicates that microgel is stable in the presence of electrolytes commonly found in soil.

[0063] FIG. 10 depicts a) germination study using five plant species (10 seeds / pot) in oven-dried sandy soil treated with different doses of microgel, and b) water retention of microgel-treated soil, and soil treated with conventional soil amendments.

[0064] FIG. 11 depicts lettuce seedlings grown in a) microgel-treated sand, and b) sand for 10 days under limited water condition (n = 3).

[0065] FIG. 12 depicts a) SEM image of Sample 1 with an average diameter of 1.75 ± 1.06 pm, b) SEM image of Sample 2 with an average diameter of 1.67±1.02 pm, and c) Particle size distribution of Sample 1 and Sample 2 dispersed in water. The average swollen diameter of Sample 1 is 18.22 pm and Sample 2 is 14.25 pm. FIG. 13 depicts a) SEM image of chitosan microgel Sample 1 with an average diameter of 2.06 ± 1 .36 pm, b) SEM image of polyvinyl alcohol (PVA) microgel Sample 2 with an average diameter of 2.33 ± 1.36 pm, c) SEM image of PVA microgel Sample 3 with an average diameter of 2.58 ± 1.1 1 pm, and d) Particle size distribution of polyacrylic acid (PAA) microgel Sample 1 and Sample 2 dispersed in water. The average swollen diameter of chitosan microgel Sample 1 is 20.6 pm, PVA microgel Sample 2 is 15.2 pm, and PVA microgel Sample 3 is 14.6 pm.

[0066] FIG. 14 depicts a) SEM image of PAA microgel Sample 1 with an average diameter of 2.01 ± 0.79 pm, and b) particle size distribution of PAA microgel Sample 1 dispersed in water. The average swollen diameter of Sample 1 is 8.2 pm.

[0067] FIG. 15 depicts a) SEM image of PVA microgel Sample 1 with an average diameter of 6.66 ± 5.51 pm, b) SEM image of PVA microgel Sample 2 with an average diameter of 6.77 ± 5.54 pm, and c) particle size distribution of PAA microgel Sample 1 and Sample 2 dispersed in water. The average swollen diameter of Sample 1 is 18.6 pm and Sample 2 is 18.40 pm.

[0068] DESCRIPTION

[0069] The present inventors have developed novel hydrogels using polycarbodiimides crosslinkers. The hydrogel swelling property and mechanical stability can be tuned by the quantity and type of polycarbodiimide used. Furthermore, polycarbodiimides are preferred over isocyanate- and epoxide-based crosslinkers in industries such as agriculture, leather and textile because they are non-toxic, non-irritant, and VOC-free. As demonstrated in the Examples of the present disclosure, the present hydrogel may find utility in agriculture - the water retaining property of the microgel outperforms commercial soil amendments such as peat and zeolite.

[0070] Thus, in a first aspect of the invention, there is provided a hydrogel comprising a crosslinked polymer formed by reaction of one or more polymers and a polycarbodiimide, wherein: the one or more polymers are selected from polymers that contain one or more carboxylic acid, hydroxyl, amino and thiol functional groups.

[0071] In embodiments herein, the word “comprising” may be interpreted as requiring the features mentioned, but not limiting the presence of other features. Alternatively, the word “comprising” may also relate to the situation where only the components / features listed are intended to be present (e.g. the word “comprising” may be replaced by the phrases “consists of” or “consists essentially of”). It is explicitly contemplated that both the broader and narrower interpretations can be applied to all aspects and embodiments of the present invention. In other words, the word “comprising” and synonyms thereof may be replaced by the phrase “consisting of” or the phrase “consists essentially of” or synonyms thereof and vice versa.

[0072] The phrase, “consists essentially of’ and its pseudonyms may be interpreted herein to refer to a material where minor impurities may be present. For example, the material may be greater than or equal to 90% pure, such as greater than 95% pure, such as greater than 97% pure, such as greater than 99% pure, such as greaterthan 99.9% pure, such as greater than 99.99% pure, such as greater than 99.999% pure, such as 100% pure.

[0073] As used herein, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a composition” includes mixtures of two or more such compositions, reference to “an oxygen carrier” includes mixtures of two or more such oxygen carriers, reference to “the catalyst” includes mixtures of two or more such catalysts, and the like.

[0074] As used herein, the term “hydrogel” refers to a broad class of polymer networks stabilized (crosslinked) either by chemical or physical methods and dispersed throughout an immobilized water phase. The hydrophilicity and stability of these polymer networks permit the penetration and absorption of water (swelling) without dissolving, thus maintaining their three-dimensional structure and function. In the currently disclosed invention, the hydrogel comprises a crosslinked polymer formed by reaction of one or more polymers and a polycarbodiimide as the crosslinker.

[0075] In certain embodiments, the one or more polymers and the polycarbodiimide may have a boiling point of greater than or equal to 220 °C. Advantageously, using polymers and polycarbodiimide with a boiling point of greater than or equal to 220 °C increases the crosslinking efficiency at typical spray drying temperatures (i.e., >120°C) as this avoids adding excess polymers / crosslinker to offset volatilization.

[0076] In certain embodiments, the one or more polymers may be selected from the group consisting of a starch, cellulose, hydroxyethyl cellulose, methyl cellulose, ethylhydroxyethyl cellulose, and more particularly, carboxymethylcellulose (CMC), chitosan, alginate, pectin, agar, polyacrylic acid, polyacrylamide, polylactic acid, and polyvinyl alcohol. In certain embodiments, the polycarbodiimide may be a polyethylene glycol-terminated polycarbodiimide. In more particular embodiments, the polyethylene glycol-terminated polycarbodiimide may be selected from one or both of:

[0077] (i)

[0078] , optionally wherein the number average molecular weight is of from 2,200 to 28,000 Daltons; and

[0079] , optionally wherein the number average molecular weight is of from 1 ,000 to 2,000 Daltons.

[0080] In certain embodiments, the polyethylene glycol-terminated polycarbodiimide may have a molecular weight selected: from 2,200 to 2,300 Daltons, from 3,700 to 3,900 Daltons, from 2,700 to 28,000 Daltons. For example, the polyethylene glycol-terminated polycarbodiimide may have a molecular weight of 3,864 Daltons. The molecular weight may be determined by conventional techniques and / or devices, such as gel permeation chromatography.

[0081] In certain embodiments, the polyethylene glycol-terminated polycarbodiimide may have a polyethylene glycol capping group having a number average molecular weight of from 100 to 500 Daltons on each end of the polycarbodiimide, such as from 200 to 400 Daltons. In more particular embodiments, the polyethylene glycol capping group may be a polyethyleneglycol methyl ether (MPRG).

[0082] The hydrogel may be in provided in any suitable forms. In certain embodiments, the hydrogel may be in the form of microgel particles. As used herein, the term “microgel” refers to an aqueous dispersions of hydrogel particles of microscale size. In certain embodiments, the particles of microgel may have an average particle size of from 0.1 to 200 pm, such as from 0.2 to 100 pm, such as from 0.3 to 50 pm, such as from 0.5 to 3 pm, such as from 1 to 2 pm, as calculated using images of particles obtained at from 1 ,000 to 5,000 magnification using a scanning electron microscope.

[0083] In certain embodiments, one or more of the following may apply:

[0084] (ai) a weight percentage attributable to the polycarbodiimide in the hydrogel relative to the total weight attributable to the one or more polymers in the hydrogel is from 0.05 to 10 wt%, such as from 0.1 to 5 wt%;

[0085] (aii) a swelling ratio (average diameter in water relative to average dry diameter) of from 350 to 2,000, such as from 400 to 1 ,738; and

[0086] (aiii) a x value of from 10 to 40%, such as from 1 1 to 30%.

[0087] As used herein, the term “x value” refers to the degree of crosslinking which quantifies the percentage of polymer chains that are interconnected in this network. Reduced network rigidity (lower x) allows easier water permeation.

[0088] As mentioned above, the present hydrogel may find utility in agriculture. Thus, in a further aspect of the invention, there is provided the following:

[0089] • an agricultural formulation comprising a hydrogel as disclosed hereinbefore;

[0090] • a use of a hydrogel as disclosed hereinbefore in crop cultivation; and

[0091] • a method of agriculture comprising the steps of:

[0092] (bi) providing a formulation comprising a hydrogel as disclosed hereinbefore;

[0093] (bii) applying the hydrogel to a growing medium that comprises a seed or a plant and growing the seed or plant to provide a desired crop product.

[0094] As details of the hydrogel have already been described above, they are omitted here for brevity.

[0095] The present inventors have also developed a method of manufacturing the present hydrogel using spray drying. Thus, in a further aspect of the invention, there is provided a method of manufacturing a hydrogel as disclosed hereinbefore, the method comprising the steps of:

[0096] (a) providing a precursor solution comprising a solvent, one or more polymers, and a polycarbodiimide; and

[0097] (b) subjecting the precursor solution to spray drying and collecting the resulting hydrogel, wherein the precursor solution has a pH that is less than or equal to 6.

[0098] As details of the hydrogel have already been described above, they are omitted here for brevity.

[0099] As used herein, the term “spray drying” refers to method of forming a dry powder from a liquid or slurry by rapidly drying with a hot gas. Typical spray dryers use some type of atomizer or spray nozzle to disperse the liquid or slurry into a controlled drop size spray. Any suitable spray dryer model may be used, such as the Mini Spray Dryer B-290 / S-300 (BUCHI Labortechnik, Switzerland), FSD 4.0 (GEA, Germany), and Spray Dryer-R / -TR / -P / -D (Preci, Japan).

[0100] As will be appreciated, the one or more polymers and the polycarbodiimide may be provided at any suitable weight percentages provided that the resultant viscosity of the precursor solution is lower than the tolerance of the spray dryer model used in the preparation.

[0101] In certain embodiments, one or more of the following may apply:

[0102] (ci) the one or more polymers are provided in an amount of from 1 to 20 % w / v, such as from 1 .5 to 7 % w / v, such as from 2 to 5 % w / v, such as about 3 % w / v in the precursor solution; (cii) the polycarbodiimide is provided in an amount of from 0.05 to 10 % w / v, such as from 0.1 to 5 % w / v in the precursor solution;

[0103] (ciii) the weight percentage of the polycarbodiimide relative to the weight of the one or more polymers if from 0.05 to 10 wt%, such as from 0.1 to 5 wt%;

[0104] (civ) a viscosity of the precursor solution is lower than the tolerance of a spray dryer model used in the preparation, for example the viscosity of the precursor solution is from 400 to 2,000 cP at 25 °C, such as from 500 to 1,200 cP at 25 °C, such as from 800 to 900 cP at 25 °C;

[0105] (cv) the precursor solution has a pH of greater than 4 and less than or equal to 6, such as from 5 to 6;

[0106] (cvi) a temperature of from 100 to 200 °C for a spray drying collection chamber, such as from 120 to 180 °C;

[0107] (cvii) a nozzle diameter for the spray dryer of from 0.1 to 5 mm, such as from 0.15 to 2.5 mm, such as from 0.2 to 1 .5 mm, such as from 0.5 to 1 .0 mm, such as about 0.7 mm.

[0108] In further embodiments, the one or more polymers may be provided in an amount of 16 % w / v in the precursor solution.

[0109] In further embodiments, the spray dryer may have a nozzle diameter of about 2.5 mm.

[0110] Without wishing to be bound by theory, a final concentration of the one or more polymers in the precursor solution may depend on a viscosity of the precursor solution. For example, a lab scale spray dryer could spray solutions up to 2000 cP, but pilot scale spray dryers could only spray <100 cP. The spray dryer used in the examples disclosed herein may have an optimum viscosity of 50 cP. In certain embodiments, wherein the precursor solution may be obtained by the steps of:

[0111] (aa) providing a pH adjusted solution of one or more polymers, where the pH of the solution is less than or equal to 6, such as from 5 to 6; and

[0112] (ab) adding the polycarbodiimide to the pH adjusted solution.

[0113] Advantageously, the present invention provides a safe, simple, and industrially scalable method for fabricating crosslinked microgels for various applications. Specifically, the present invention demonstrates that the spray dried microgels disclosed herein can be used as soil conditioning agent due to its ability to retain large amount of water (swelling ratio >400). As a soil conditioner, the spray dried microgels are:

[0114] • environmental: the biopolymers used to fabricate the microgel are Generally Recognized as Safe (GRAS) by the US Food and Drug Administration. The microgel or its post-degradation byproducts does not pose cyto- and / or nano-toxicity to plants;

[0115] • ease of use: the microgel easily penetrates the topsoil after application eliminating the need for tilling / churning the soil;

[0116] • edge over competitors: the microgel has two functions when applied to soil - conditioning and water retention. Closest competitors offer either soil conditioning formulations comprising only of surfactants or water retention formulation comprising of gels. Furthermore, the microgel can enrich the organic matter of the soil when completely degraded; and

[0117] • versatility: synthesis setup is versatile to include subsequent product variations (nutrient formulation / biocide formulation).

[0118] Further aspects and embodiments of the invention will now be discussed by reference to the following non-limiting examples.

[0119] EXAMPLES

[0120] Materials

[0121] Propylene glycol methyl ether acetate, diisocyanate monomer and polyethylene glycol monomethyl ether (MPEG) were purchased from Sigma-Aldrich. 3-methyl-1 -phenyl-2- phospholene-1 -oxide catalyst was purchased from TCI. The remaining materials were obtained from commercial sources and used without purification unless otherwise stated.

[0122] Analytical techniques GPC Method

[0123] The average molecular weight of the polyethylene glycol-terminated polycarbodiimide was determined using gel permeation chromatography (GPC). GPC 1260 system with Agilent 1260 HPLC pump and an Agilent 1260 refractive index detector were used for the analysis. Moreover, the analysis used a polystyrene-divinylbenzene column (Agilent PLGel, Particle Size: 5 pm, Pore size: 103 A, PL1110-6530) with tetrahydrofuran (THF) as the eluent at a flow rate of 1 mL / min at 40 °C.

[0124] Swelling ratio measurement technique

[0125] The swelling ratio (SR) of the microgels was determined using Equation 1. The average diameter of the swollen microgels in aqueous conditions (ds) was measured using Partica LA- 960 particle size analyzer (Horiba, Japan). Sufficient amount of the sample was diluted in the solvent to achieve a laser obscuration level of 7-10%. Subsequently, the average diameter of the dried microgels (dd) were determined through SEM using a JSM FE-SEM 7600F (Jeol Ltd., Japan). The microgel samples were fixed on conductive carbon tapes and sputter-coated with Au for 30 seconds at 20 mA before collecting the SEM images at high magnification with an accelerating voltage of 5-15 kV. The diameter of 100 particles was manually measured using ImageJ (NIH, USA) and averaged to get the ddof each formulation. Also, the optical image of the swollen microgels dispersed in aqueous media was collected using optical light microscopy at x60 magnification.

[0126] The swelling of the microgel in various pH buffers and electrolytes solutions was assessed to evaluate the performance at various conditions and crosslinking stability. The swelling experiment utilized buffer solutions including 10 mM sodium acetate-acetic acid (pH 4.0-5.0), 10 mM potassium phosphate (pH 6.0-8.0), and 10 mM carbonate-bicarbonate (pH 9.0-10.0). Next, 0.1 g microgel was dissolved in 250 mL buffer solution and equilibrated for 1 h with constant stirring. For pH 2.0 and 3.0, the 0.1 g microgel was dissolved in 250 mL deionized water and the pH was adjusted using dilute HCI.

[0127] Example 1. Preparation of swellable microgel using spray drying technique

[0128] Currently, there is no report on the use of polycarbodiimide to fabricate crosslinked hydrogels or microgels. The present invention describes the preparation of swellable microgel using spray drying technique. The process consists of 1 ) preparing a feed solution, 2) adjusting the pH, 3) mixing the polymeric crosslinker into the polymer mixture, 4) spray drying under preset condition, and 5) collection of microgel particles. The feed polymer solution contains a polymer or a mixture of polymer containing carboxylic acid-, hydroxyl-, amine-, and / or thiol-group such as carboxymethyl cellulose, cellulose derivatives, chitosan, alginate, pectin, agar, polyacrylic acid, polyacrylamide, polylactic acid, polyvinyl alcohol.

[0129] The polymer was dissolved in water to prepare a solution with viscosity lower than the tolerance of the spray dryer model. The pH of the feed solution was adjusted to pH < 6.0 using a dilute acid solution. Finally, polyethylene glycol terminated polycarbodiimide (PCD) with Mw between 1500 to 27908 was added into the mixture to make a final concentration of 0.1 -5.0%. FIG. 1 summarizes the synthesis route and chemical properties of polyethylene glycol- terminated polycarbodiimide used in the present invention.

[0130] Table 1 . Properties of polyethylene glycol terminated PCD crosslinker used to prepare the polymer microgels.

[0131] In one embodiment of the invention, 0.6 mg PCD 1 (x = 0.03) was added into 20 mL 3% (w / v) carboxymethyl cellulose (viscosity = 837 cP) at pH 5.0. The mixture was stirred at 450 rpm for 5 min. The mixture was then fed to a Mini Spray Dryer B-290 (BUCHI Labortechnik, Switzerland) at a rate of 3.0 mL min1. The polymer mixture was aspirated at a flow rate of 819 L IT1through a 0.7 mm nozzle with the drying chamber set at 120 °C. The dried carboxymethyl cellulose microgel was then collected, stored, and characterized.

[0132] Synthesis of polycarbodiimide crosslinker

[0133] For the synthesis of polycarbodiimide crosslinker, 40-89 mol% propylene glycol methyl ether acetate, 0.28-0.45 mol% 3-methyl-1 -phenyl-2-phospholene-1 -oxide catalyst and 16-33 mol% diisocyanate monomer were mixed and transferred into a 25 mL three-neck round bottom flask. The mixture was sparged with N2gas and heated at 150 °C for 60-120 min with constant stirring. Next, 17-29 mol% MPEG was added to the mixture. The mixture was re-sparged with N2gas for 15 min and heated at 115 °C for 60 min.

[0134] Synthesis of PCD-CMC microgels / polymer feed solution is prepared by dissolving a water- soluble polymer in deionized water to a desired concentration. A crosslinking agent is then added to the solution at an appropriate concentration, and the pH of the resulting mixture is adjusted to a target value, such as pH 5.0, 6.0, or 7.0, using suitable acidic or basic reagents. The homogeneous feed solution is subsequently spray-dried using a laboratory-scale spray dryer, such as a Mini Spray Dryer B-290 (BUCHI Labortechnik) or an equivalent apparatus. The spray dryer is equipped with a two-fluid coaxial nozzle having an orifice diameter of approximately 0.7 mm. The feed solution is introduced into the spray dryer at a flow rate of about 3 mL / min, and nitrogen gas is used as the atomizing medium at a flow rate of approximately 819 L / h. The drying chamber is aspirated at a rate of about 35 m3 / h to facilitate particle collection. Throughout the process, the inlet temperature is maintained at approximately 120°C. The resulting dried material is collected and may be stored under appropriate conditions to preserve its properties. This method may be applied to various polymer and crosslinker systems, with process parameters adapted as necessary to achieve the desired product characteristics.

[0135] Characterization

[0136] Particle size analysis of SEM images collected at 5000 magnification revealed that the average particle size is 1.84 ± 1.02 pm (FIG. 2a). Dispersing the in deionized water results in the particle swelling 1284 times with a final swollen diameter of 20.0 pm (FIG. 2b).

[0137] Example 2. Effect of pH of the mixture on crosslinking

[0138] FTIR and XPS analysis

[0139] IR spectra of the samples were collected between 4000 and 400 erm1using Frontier FT-IR (PerkinElmer, USA). Transmission mode was used to collect the IR spectra of the samples at 1 erm1resolution. XPS was used to determine the degree of crosslinking (x) of polycarbodiimide-crosslinked CMC samples. Wide and high resolution XPS spectra were collected using a Kratos AXIS Supra (Al Ka source, 225 W) over an analysis area of 700 x 300 pm2 with a takeoff angle of 90°. All spectra were BE corrected using the C-C component at 285.0 eV of C 1s based on Beamson and Briggs. The x was computed from the ratio of atomic concentration (%) of ureide N 1s at 400.3 eV and cellulosic Ca at 288.1 eV (Equation 1). which was respectively obtained from the peak-fitted area of the core levels scaled by the relative sensitivity factor (RSF). N — Ureide (%) y = - (1) cellulosic Ca(%)

[0140] Results and discussion

[0141] To test the effect of pH of the mixture on crosslinking, 20 mL 3% (w / v) carboxymethyl cellulose (viscosity = 837 cP) at pH 4.0, 5.0, 6.0, 7.0 and 8.0 were prepared. 15 mg PCD 1 was added to each solution and was then stirred at 450 rpm. FIG. 3 shows the FTIR spectra of the dried PCD-CMC mixtures at pH 4.0 to pH 8.0 were collected to determine the optimum pH to initiate crosslinking. Both -N=C=N- stretch at 2128 cm1and -C=O stretch at 1600 cnr1is shown to decrease with pH (FIG. 3b). Moreover, N-acylurea C=O stretch at 1657 erm1is shown to increase with acidification. There was a noticeable increase in viscosity mixture for samples at pH < 6.0 after the addition of the crosslinker. Unfortunately, the mixture at pH 4.0 became too viscous to spray dry using the built in peristaltic pump (Buchi B-290, silicone tube inner diameter: 2.0 mm). FIG. 4 shows that adjusting the mixture pH to 6.0 was sufficient to initiate the crosslinking.

[0142] Example 3. Effect of temperature on the particle formation

[0143] The effect of temperature on the particle formation was studied in an embodiment of the present invention. 30 mg PCD 1 was added into 20 mL 3% (w / v) carboxymethyl cellulose (viscosity = 837 cP) at pH 5.0. The mixture was stirred at 450 rpm for 5 min. Different mixtures were spray dried at 120-180 °C while keeping the rest of the spray drying parameters constant. The dried cellulose microgel was then collected, stored, and characterized.

[0144] Results and discussion

[0145] The average particle diameter and swollen diameter in deionized water of samples were found to be 1.84-2.01 pm and 14.41 -14.84 pm, respectively (FIG. 5). Calculated swelling ratio of samples spray dried at 120 °C, 140 °C, 160 °C, and 180 °C were found to be 497, 402, 435, and 404, respectively (FIG. 6).

[0146] Example 4. Effect of PCD dosage on the particle formation and swelling of the microgel

[0147] In a separate embodiment of the invention, the effect of PCD dosage on the particle formation and swelling of the microgel was investigated. PCD-CMC mixtures containing 0.1 %, 0.25%, 0.5%, 1 .0%, 2.5%, and 5% PCD 1 were spray dried at 120 °C. FIG. 7 shows that increasing the PCD dosage decreases swelling and promotes particle aggregation in deionized water. Swelling ratio of spray dried microgel using 0.1%, 0.25%, 0.5%, 1.0%, 2.5%, and 5% PCD 1 were 2359, 1563, 798, 588, 478, and 471 , respectively. The swelling ratio of PCD-CMC microgels coincides with their corresponding x values. FIG. 8a shows that the swelling ratio values of PCD-CMC microgel with x =25% and x =30% plateaued at -500. An enhancement in the swelling ratio to 589 of the microgel was first observed once the x decreased to 23%. Further decreasing the x dramatically enhanced the swelling ratio value, with the highest being 2359 corresponding to microgel with x =11%.

[0148] It was determined that the deprotonation of the -COOH group (pKa -4.5) leads to greater chain repulsion and degree of swelling. The microgel dispersed in pH 2.0-10 buffer solution also displayed pH-responsive swelling. However, the chemical nature of the crosslinking may have caused the lowering of the pKa value of -COOH, causing the favorable swelling at a much lower pH. FIG. 8b shows that the swelling ratio value of microgel was initially 1036 at pH 2.0, gradually increases to 1511 at pH 3.0 until it reaches a maximum value of 1738 at pH 4.0. It is possible that the pKa value of -COOH of the CMC chain was substantially lowered by the ureide linkage which is an electron-withdrawing substituent. This is advantageous for soil conditioning applications. The soil pH can range from 3.5 to 9.0 depending on its organic and inorganic contents. Based on FIG. 8b, the microgel is able to fully swell within this pH range and, therefore, can offer maximum water retention regardless of soil composition. The high swelling potential of the spray dried PCD-CMC microgels makes them suitable for a various application (e.g. absorptive material, soil conditioner, encapsulation material).

[0149] Example 5. Effect of ions on the swelling of the microgel

[0150] Evaluation of microgel swelling in electrolyte solutions

[0151] The microgel swelling in electrolyte solutions was evaluated using 10-75 mM of NaCI, CaCl2, and MgCk solutions. For the swelling experiment, 0.1 g microgel was dispersed in 250 mL electrolyte solution for 1 h with constant stirring. The resulting dispersions were then measured using the Partica LA-960 particle size analyzer.

[0152] Results and discussion

[0153] The potential of ions presents in soil, such as Na+and Mg2+, to disrupt the swelling of the microgel has been evaluated. The PCD-CMC microgel dispersed in electrolyte solutions shows great stability in various degree of salinity (FIG. 9). The minimal reduction (-10%) in its swollen diameter due to the “charge screening effect” across a wide salinity range indicates that the microgel can retain moisture even in very saline conditions. Example 6. Germination of plants with different doses of PCD-CMC microgel

[0154] Germination study

[0155] FIG. 10a shows the germination of Amaranth, Cai Xin, Chinese Mustard, Huang Jing Bai Cai, and Xiao Bai Cai sown in soil (control) and soil treated with different doses of PCD-CMC microgel (Dose 2 > Dose 1 ) after 5 days and 7 days. Each pot contained 20 g medium (60 °C oven-dried sandy soil), and three pots were prepared for each of the five species. For each species, 10 seeds were planted with equal spacing (e.g. 2-3-3-2 seeding formation across 4 equally-spaced horizontal rows) into each of the three pots, and each pot was watered to saturation using identical volumes of either water (“control”), recommended dose (“Dose 1”) or double strength (“Dose 2”) of RetenSol-G microgel formulation on day 0. All pots did not receive any subsequent watering, and the differences and changes in seed germination were documented over 7 days. After 5 days, the germination rate for the control was found to be 0- 40% versus 70-100% for microgel-treated soil. The limited water supply resulted in the withering of seedling grown in regular soil after 7 days. On the other hand, seedlings grown in the microgel treated soil were able to endure the lack of irrigation. This suggests that the microgel had a positively effect on the growth of the five plant species despite the limited water supply. Moreover, FIG. 10b shows the water retention of microgel-treated soil is superior compared to conventional soil amendments like peat and zeolite.

[0156] Results and discussion

[0157] Based on the results, we anticipated other potential functions of the spray dried microgel other than to improve survivability of plants and crops during limited water conditions. Treating soil with the microgel can reduce the irrigation frequency and improve the water use efficiency (WUE) of crops. It also presents an opportunity to cultivate crops in undesirable growth media like sand. FIG. 11 shows that treating sand with the microgel formulation was able to improve the survival of lettuce and reduce water stress under limited water supply. Currently, hydrogel formulation promising similar functions are based on synthetic polymers and come in granulated form.

[0158] Example 7. Crosslinked alginate microgel

[0159] Feed solutions containing 30 mg / mL sodium alginate (Mw = 40 kDa) in buffer / acid solution and 0.25% PCD 2 were spray dried (Mini Spray Dryer B-290, BUCHI Labortechnik) at 3 mL / min (Table 2). A two-fluid coaxial nozzle with 0.7 mm diameter was used to spray dry the feed solution. The solutions were atomized using N2gas at 819 L / h flow rate and aspirated to the collection chamber at a rate of 35 m3 / h. The inlet temperature was maintained at 120 °C for the duration of the spray drying process.

[0160] Table 2. Feed formulation of spray dried alginate microgel crosslinked using the polymeric crosslinker.

[0161] Characterization

[0162] FIG. 12 shows the characterization of crosslinked alginate microgels. Comparative Example 1

[0163] Table 3 shows a comparative analysis of the microgel formulation disclosed herein against commercial hydrogel formulations. Table 3. Technical details of the current microgel technology and existing commercial hydrogels used as a soil conditioner.

[0164] Example 8. Crosslinked chitosan microqels, polyacrylic acid (PAA) microqels and polyvinyl alcohol (PVA) microqels Crosslinked chitosan microqels

[0165] Feed solutions containing 20 mg / mL chitosan in 2% acetic acid and 0.17% PCD 1 were spray dried (Mini Spray Dryer S-300, BUCHI Labortechnik) at 3 mL / min (Table 4). The pH of the solution was adjusted 0.1 M NaOH. A two-fluid coaxial nozzle with 0.7 mm diameter was used to spray dry the feed solution. The solutions were atomized using N2gas at 1700 L / h flow rate and aspirated to the collection chamber at a rate of 35 m3 / h. The inlet temperature was maintained at 140 °C for the duration of the spray drying process.

[0166] Table 4. Feed formulation of spray dried chitosan microgel crosslinked using the polymeric crosslinker. Crosslinked polyacrylic acid (PAA) microgels

[0167] Feed solutions containing 20 mg / mL PAA in deionized water and 0.17% PCD 1 were spray dried (Mini Spray Dryer S-300, BUCHI Labortechnik) at 3 mL / min (Table 5). The pH of the solution was adjusted 0.1 M NaOH. A two-fluid coaxial nozzle with 0.7 mm diameter was used to spray dry the feed solution. The solutions were atomized using N2gas at 1700 L / h flow rate and aspirated to the collection chamber at a rate of 35 m3 / h. The inlet temperature was maintained at 140 °C for the duration of the spray drying process.

[0168] Table 5. Feed formulation of spray dried PAA microgel crosslinked using the polymeric crosslinker.

[0169] Crosslinked polyvinyl alcohol (PVA) microgels

[0170] Feed solutions containing 50 mg / mL PVA in deionized water and 0.42% PCD 1 were spray dried (Mini Spray Dryer S-300, BUCHI Labortechnik) at 3 mUmin (Table 6). The pH of the solution was adjusted 0.1 M acetic acid. A two-fluid coaxial nozzle with 0.7 mm diameter was used to spray dry the feed solution. The solutions were atomized using N2gas at 1700 L / h flow rate and aspirated to the collection chamber at a rate of 35 m3 / h. The inlet temperature was maintained at 140 °C for the duration of the spray drying process.

[0171] Table 6. Feed formulation of spray dried PVA microgel crosslinked using the polymeric crosslinker.

[0172] Characterization

[0173] FIGS. 13-15 show the characterization of crosslinked chitosan, PAA and PVA microgels. Conclusion

[0174] This present invention provides a novel method for spray drying microgels using water soluble polycarbodiimides crosslinker. In an embodiment of the invention, microgels were prepared by adding at least 0.1% (w / v) polycarbodiimide into the 3% (w / v) carboxymethyl cellulose solution (pH < 6.0) and spray drying the mixture at > 100 °C. The microgel swelling property and mechanical stability can be tuned by the quantity and type of polycarbodiimide used. Furthermore, the potential application of these microgels as a soil conditioner was demonstrated. The results show that the water retaining property of the microgel outperforms commercial soil amendments such as peat and zeolite.

Claims

Claims1. A hydrogel comprising a crosslinked polymer formed by reaction of one or more polymers and a polycarbodiimide, wherein: the one or more polymers are selected from polymers that contain one or more carboxylic acid, hydroxyl, amino and thiol functional groups.

2. The hydrogel according to claim 1 , wherein the one or more polymers and the polycarbodiimide have a boiling point of greater than or equal to 220 °C.

3. The hydrogel according to Claim 1 or Claim 2, wherein the one or more polymers are selected from the group consisting of a starch, cellulose, hydroxyethyl cellulose, methyl cellulose, ethylhydroxyethyl cellulose, and more particularly, carboxymethylcellulose (CMC), chitosan, alginate, pectin, agar, polyacrylic acid, polyacrylamide, polylactic acid, and polyvinyl alcohol.

4. The hydrogel according to any one of the preceding claims, wherein the polycarbodiimide is a polyethylene glycol-terminated polycarbodiimide.

5. The hydrogel according to Claim 4, wherein the polyethylene glycol-terminated polycarbodiimide is selected from one or both of:(i), optionally wherein the number average molecular weight is of from 2,200 to 28,000 Daltons; and, optionally wherein the number average molecular weight is of from 1 ,000 to 2,000 Daltons.

6. The hydrogel according to Claim 5, wherein the polyethylene glycol-terminated polycarbodiimide of Claim 5(i) has a molecular weight selected: from 2,200 to 2,300 Daltons, from 3,700 to 3,900 Daltons, from 2,700 to 28,000 Daltons.

7. The hydrogel according to any one of Claims 4 to 6, wherein the polyethylene glycol- terminated polycarbodiimide has a polyethylene glycol capping group having a number average molecular weight of from 100 to 500 Daltons on each end of the polycarbodiimide, such as from 200 to 400 Daltons, optionally wherein the polyethylene glycol capping group is a polyethyleneglycol methyl ether (MPRG).

8. The hydrogel according to any one of the preceding claims, wherein the hydrogel is in the form of microgel particles.

9. The hydrogel according to Claim 8, wherein the particles of microgel have an average particle size of from 0.1 to 200 pm, such as from 0.2 to 100 pm, such as from 0.3 to 50 pm, such as from 0.5 to 3 pm, such as from 1 to 2 pm, as calculated using images of particles obtained at from 1 ,000 to 5,000 magnification using a scanning electron microscope.

10. The hydrogel according to any one of the preceding claims wherein one or more of the following apply:(ai) a weight percentage attributable to the polycarbodiimide in the hydrogel relative to the total weight attributable to the one or more polymers in the hydrogel is from 0.05 to 10 wt%, such as from 0.1 to 5 wt%;(aii) a swelling ratio (average diameter in water relative to average dry diameter) of from 350 to 2,000, such as from 400 to 1 ,738; and(aiii) a x value of from 10 to 40%, such as from 11 to 30%.

11. An agricultural formulation comprising a hydrogel according to any one of Claims 1 to 10.

12. Use of a hydrogel according to any one of Claims 1 to 10 in crop cultivation.

13. A method of agriculture comprising the steps of:(bi) providing a formulation comprising a hydrogel according to any one of Claims 1 to 10; (bii) applying the hydrogel to a growing medium that comprises a seed or a plant and growing the seed or plant to provide a desired crop product.

14. A method of manufacturing a hydrogel according to any one of Claims 1 to 10, the method comprising the steps of:(a) providing a precursor solution comprising a solvent, one or more polymers, and a polycarbodiimide; and(b) subjecting the precursor solution to spray drying and collecting the resulting hydrogel, wherein the precursor solution has a pH that is less than or equal to 6.

15. The method according to Claim 14, wherein the one or more polymers and the polycarbodiimide have a boiling point of greater than or equal to 220 °C.

16. The method according to Claim 14 or Claim 15, wherein the one or more polymers are selected from the group consisting of a starch, cellulose, hydroxyethylcellulose, methyl cellulose, ethylhydroxyethyl cellulose, and more particularly, carboxymethylcellulose (CMC), chitosan, alginate, pectin, agar, polyacrylic acid, polyacrylamide, polylactic acid, and polyvinyl alcohol.

17. The method according to any one of Claims 14 to 16, wherein the polycarbodiimide is a polyethylene glycol-terminated polycarbodiimide, optionally wherein the polyethylene glycol capping group is a polyethyleneglycol methyl ether (MPRG).

18. The method according to Claim 17, wherein the polyethylene glycol-terminated polycarbodiimide is selected from one or both of:(i), optionally wherein the number average molecular weight is of from 2,200 to 28,000 Daltons; and, optionally wherein the number average molecular weight is of from 1 ,000 to 2,000 Daltons.

19. The method according to Claim 18, wherein the polyethylene glycol-terminated polycarbodiimide of Claim 5(i) has a molecular weight selected: from 2,200 to 2,300 Daltons, from 3,700 to 3,900 Daltons, from 2,700 to 28,000 Daltons.

20. The method according to any one of Claims 14 to 19, wherein the polyethylene glycol- terminated polycarbodiimide has a polyethylene glycol capping group having a number average molecular weight of from 100 to 500 Daltons on each end of the polycarbodiimide, such as from 200 to 400 Daltons.21 . The method according to any one of Claims 14 to 20, wherein the hydrogel is collected in the form of microgel particles.

22. The method according to any one of Claims 14 to 21 , wherein one or more of the following apply:(ci) the one or more polymers are provided in an amount of from 1 to 20 % w / v, such as from 1 .5 to 7 % w / v, such as from 2 to 5 % w / v, such as about 3 % w / v in the precursor solution; (cii) the polycarbodiimide is provided in an amount of from 0.05 to 10 % w / v, such as from 0.1 to 5 % w / v in the precursor solution;(ciii) the weight percentage of the polycarbodiimide relative to the weight of the one or more polymers if from 0.05 to 10 wt%, such as from 0.1 to 5 wt%;(civ) a viscosity of the precursor solution is lower than the tolerance of a spray dryer model used in the preparation, for example the viscosity of the precursor solution is from 400 to 2,000 cP at 25 °C, such as from 500 to 1,200 cP at 25 °C, such as from 800 to 900 cP at 25 °C;(cv) the precursor solution has a pH of greater than 4 and less than or equal to 6, such as from 5 to 6(cvi) a temperature of from 100 to 200 °C for a spray drying collection chamber, such as from 120 to 180 °C;(cvii) a nozzle diameter for the spray dryer of from 0.1 to 5 mm, such as from 0.15 to 2.5 mm, such as from 0.2 to 1 .5 mm, such as from 0.5 to 1 .0 mm, such as about 0.7 mm.

23. The method according to any one of Claims 14 to 22, wherein the precursor solution is obtained by the steps of:(aa) providing a pH adjusted solution of one or more polymers, where the pH of the solution is less than or equal to 6; and(ab) adding the polycarbodiimide to the pH adjusted solution.

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