EP-4735042-A1 - MERCERIZED DECELLULARIZED PARTICLES FOR SLOW RELEASE APPLICATIONS AND METHODS THEREOF

Abstract

A method of providing a slow, controlled or sustained release of a compound of interest such as biomolecules or drugs is provided. The method involves incubating the compound of interest with mercerized decellularized cellulose particles for a predetermined amount of incubation time to allow the mercerized decellularized cellulose particles to absorb the compound of interest. Thereafter, the method involves adjusting a physical or chemical property of the decellularized particles to trigger, alter, enable or affect the slow, controlled or sustained release of the compound of interest. Mercerized decellularized particles and formulations for slow, controlled or sustained release of compounds of interest are also provided.

Inventors

• HICKEY, RYAN
• DE SANTE, Stephanie
• ODDING, Joseph Christopher Samuel
• PELLING, Andrew
• TISCHER, Paula Cristina De Sousa Faria
• SAMSON, Briana
• NHAN, Jordan
• CRAWFORD, Natalie
• BYRNS, Megan

Assignees

• Spiderwort Biotechnologies Inc.

Dates

Publication Date

20260506

Application Date

20240628

Claims (20)

1. 1 . A method of providing a slow, controlled or sustained release of a compound of interest: (a) incubating the compound of interest with mercerized decellularized cellulose particles for a predetermined incubation time; and (b) adjusting a physical or a chemical property of the mercerized decellularized cellulose particles to trigger, alter, enable or affect the slow, controlled or sustained release of the compound of interest.
2. 2. The method of claim 1 , wherein the predetermined incubation time allows the cellulose particles to absorb the compound of interest and ranges from 1-96 hours.
3. 3. The method of claim 1 or 2, wherein the method additionally comprises: (c) adjusting a physical or a chemical property of the compound of interest to trigger, alter, enable or affect the slow, controlled or sustained release of the compound of interest.
4. 4. The method of claim 1 , wherein the method additionally comprises: (d) pretreating the cellulose particles to trigger, alter, enable or affect the slow, controlled or sustained release of the compound of interest or to adjust the release kinetics of the compound of interest.
5. 5. The method of any one of claims 1-4, wherein the method comprises: mixing, soaking or centrifuging the mercerized decellularized cellulose particles and the compound of interest to prepare a mixture prior to step (a).
6. 6. The method of claim 5, wherein the mixing, soaking or centrifuging promotes absorption of the compound of interest on to the cellulose particles
7. 7. The method of any one of claims 1-5, wherein the mixing, soaking or centrifuging step occurs in the presence of a solvent.
8. 8. The method of claim 7, wherein the solvent is water, saline, or PBS.
9. 9. The method of any one of claims 1-8, wherein the method additionally comprises: (d) adjusting a physical or a chemical property of the mixture to trigger, alter, enable or affect the slow, controlled or sustained release of the compound of interest.
10. 10. The method of claim 1 or 3, wherein the method comprises modulating the physical or the chemical property of the mercerized decellularized cellulose particles, the compound of interest and/or the mixture to control the release pattern of the compound of interest.
11. 11 . The method of claim 1 , wherein step (b) comprises: adjusting pKa of the cellulose particles to trigger, alter, enable or affect the slow, controlled or sustained release of the compound of interest.
12. 12. The method of claim 1 , wherein step (b) comprises: adjusting pH of the cellulose particles to trigger, alter, enable or affect the slow, controlled or sustained release of the compound of interest.
13. 13. The method of claim 1 , wherein step (b) comprises: adjusting concentration of the cellulose particles to trigger, alter, enable or affect the slow, controlled or sustained release of the compound of interest.
14. 14. The method of claim 1 , wherein step (b) comprises: modifying chemical structure of the cellulose particles to trigger, alter, enable or affect the slow, controlled or sustained release of the compound of interest.
15. 15. The method of claim 1 , wherein step (b) comprises: modifying crystal structure of the cellulose particles to trigger, alter, enable or affect the slow, controlled or sustained release of the compound of interest.
16. 16. The method of claim 15, wherein modifying the chemical structure of the mercerized decellularized cellulose particles comprises: succinylating the mercerized decellularized cellulose particles.
17. 17. The method of claim 15, wherein modifying the chemical structure of the mercerized decellularized cellulose particles comprises: adding a charge on the mercerized decellularized cellulose particles.
18. 18. The method of claim 16 or 17, wherein step (b) additionally comprises: preparing a combination mixture of the modified mercerized decellularized cellulose particles and the unmodified mercerized decellularized cellulose particles; and adjusting a physical or a chemical property of the combination mixture to trigger, alter, enable or affect the slow, controlled or sustained release of the compound of interest.
19. 19. The method of claim 18, wherein the combination mixture comprises the modified cellulose particles and the unmodified cellulose particles in a fixed ratio.
20. 20. The method of claim 2, wherein step (c) comprises adjusting size of the compound of interest to trigger, alter, enable or affect the slow, controlled or sustained release of the compound of interest.

Description

MERCERIZED DECELLULARIZED PARTICLES FOR SLOW RELEASE APPLICATIONS AND METHODS THEREOF FIELD OF THE INVENTION [1 ] This invention relates to mercerized decellularized formulations for slow, controlled, or sustained release applications. More specifically, this invention relates to mercerized decellularized particles and methods of providing slow, controlled, or sustained release of a compound of interest. BACKGROUND OF THE INVENTION [2] A controlled release of compounds is desired to elicit specific biological responses or to provide continued and time-resolved therapeutic treatments. It has widespread applications in bioengineering for drug and gene delivery. Apart from these, slow or controlled release of biomolecules are also desired in tissue engineering applications. [3] Presently, microencapsulation, diffusion systems, dissolution systems, osmotic systems, ion-exchanges, gastric floating systems, bio-adhesive systems, and matrix systems are being used to manipulate release kinetics of biomolecules. These current strategies rely on several secondary components and external factors to achieve the desired functionality. Additionally, they pose several issues and are not optimum for slow release applications. [4] Therefore, there is a need of a better solution to achieve the slow release functionality with a system that is reproducible and is capable of delivering biomolecules at the desired rate kinetics. SUMMARY OF THE INVENTION [5] The invention describes a method of providing a slow, controlled or sustained release of a compound of interest. The method mainly involves a step of incubating or mixing the compound of interest with mercerized decellularized cellulose particles for a predetermined incubation time. This step is followed by a step of adjusting or manipulating a physical or a chemical property of the mercerized decellularized cellulose particles, the compound of interest, or a mixture of both, to trigger, alter, enable or affect the slow, controlled or sustained release of the compound of interest. [6] The invention also describes a method of providing a slow, controlled or sustained release of lidocaine, ibuprofen, RGD-motif, tryptophan, acetaminophen, diclofenac, gentamicin, hyaluronic acid, naproxen, albumin, lysozyme, somatostatin, and insulin. The method involves a step of incubating the target compound with mercerized decellularized cellulose particles for a predetermined incubation time, where the predetermined incubation time may range from 1-96 hours. The method further involves a step of adjusting or manipulating a physical or a chemical property of the mercerized decellularized cellulose particles to trigger, alter, enable or affect the slow, controlled or sustained release of the target compound in the patient. [7] The invention also describes cellulose particles for slow, controlled or sustained release of a pre-absorbed compound of interest. The cellulose particles may be mercerized and could be derived from a decellularized plant material known in the art such as apple, banana, mango or pear. A formulation that comprises or contains the cellulose particles recited above along with a physiologically acceptable component is also described. BRIEF DESCRIPTION OF DRAWINGS [8] Figure 1 shows a graph of lidocaine slow release from mercerized cellulose after a 24 h incubation with the lidocaine where the absorbance was measured at 290 nm. [9] Figure 2 shows a graph of lidocaine slow release from mercerized cellulose particles for different preincubation times, where grey bar = 24 h, blue bar = 48 h, and pink bar = 72 h. [10] Figure 3 shows a graph of lidocaine slow release from mercerized cellulose particles for different preincubation times where grey bar = 24 h, blue bar = 48 h, and pink bar = 72 h. [1 1] Figure 4 shows a graph of lidocaine release from unmodified mercerized decellularized material and succinylated mercerized decellularized material at pH 6.8 and 7.2. [12] Figure 5 shows a slow release of ibuprofen from 4.5% mercerized decellularized cellulose-based particles. [13] Figure 6 shows a slow release of ibuprofen from 4.5% mercerized decellularized cellulose-based particles with the exponential fit beginning on day 5. [14] Figure 7 shows a slow release of tryptophan from 4.5% mercerized decellularized cellulose-based particles. [15] Figure 8 shows a slow release of tryptophan from 4.5% mercerized decellularized cellulose-based particles with the exponential fit beginning on day 2. [16] Figure 9 shows slow release of RGD from 4.5% mercerized decellularized cellulose-based particles. [17] Figure 10 shows standard curve for bovine serum albumin where the data points represent the mean of triplicate readings and standard error of the mean. [18] Figure 11 shows standard curve for lysozyme where the data points represent the mean of triplicate readings and standard error of the mean. [19] Figure 12 shows a standard curve for somatostatin-14 where the data points represent the