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US-12624173-B2 - Biodegradable polymeric compositions, methods of preparation and uses thereof

US12624173B2US 12624173 B2US12624173 B2US 12624173B2US-12624173-B2

Abstract

Disclosed herein compositions of polysaccharides chemically cross-linked by aromatic dialdehydes. The compositions may be in form of polymeric sheets for a variety of applications. Disclosed also nano-sized particles comprising the polysaccharide chemically cross-linked by aromatic dialdehydes. The nano-sized particles may further comprise lipids and surfactants. Intranasal delivery of the nano-sized particles enables delivery of biologically active agents into the brain. Topical and transdermal delivery of the nano-sized particles enables delivery of biologically active agents for treatment of systemic or dermatological disorders. Methods of manufacturing and uses of the compositions are also disclosed.

Inventors

  • Amnon Sintov

Assignees

  • B.G. NEGEV TECHNOLOGIES AND APPLICATIONS LTD., AT BEN-GURION UNIVERSITY

Dates

Publication Date
20260512
Application Date
20220531

Claims (10)

  1. 1 . A composition of matter comprising starch chemically crosslinked by divanillin, and a bioactive material, which is an antibody drug conjugate, or a peptide drug conjugate.
  2. 2 . The composition of claim 1 , in the form of a polymeric sheet, or a polymeric particle/capsule.
  3. 3 . The composition of claim 1 , which is a pharmaceutically acceptable formulation.
  4. 4 . The composition of claim 1 , in the form of nano-sized particles.
  5. 5 . The composition of claim 1 , further comprising a lipid and/or a surfactant and/or a cosolvent.
  6. 6 . The composition of claim 5 , wherein the lipid and/or a surfactant and/or a cosolvent are selected from the group consisting of caprylocaproyl polyoxyl-8 glyceride, polyoxyl-40 hydrogenated castor oil, propylene carbonate, tetraglycol, glyceryl oleate and dioleate, isopropyl palmitate, and cocoa butter.
  7. 7 . The composition of claim 6 , wherein the lipid and/or a surfactant and/or a cosolvent comprises at least one member of the group consisting of polyoxyl-40 hydrogenated castor oil, tetraglycol, and glyceryl oleate.
  8. 8 . The composition of claim 7 , wherein the lipid and/or a surfactant and/or a cosolvent comprises polyoxyl-40 hydrogenated castor oil.
  9. 9 . The composition of claim 7 , wherein the lipid and/or a surfactant and/or a cosolvent comprises tetraglycol.
  10. 10 . The composition of claim 7 , wherein the lipid and/or a surfactant and/or a cosolvent comprises glyceryl oleate.

Description

BACKGROUND OF THE INVENTION In the last two decades, the worldwide demand for environmentally friendly materials in most fields of day-to-day life was vastly increased due to a deeper understanding of the risks and the extensive damage to both human health and the disastrous environmental effects. The use of biodegradable materials in the place of traditional petroleum-based plastic polymers has increased, and the efforts directed to find mechanically stable and robust alternatives are extensively studied. The most common biodegradable materials utilized today are polyhydroxyalkanoates, for example, polyhydroxy 3-butyrate (PHB), starch blends and cellulose based materials. Different combinations and chemical processes were developed over the years in order to promote the use of biodegradable materials and their incorporation into the industry, for example, as an alternative for nylon bags and packaging material for food products. Biodegradable materials also found extensive use in biomedical devices, tissue engineering and other applications, e.g. sutures, surgical fixation devices and drug delivery. To date, polymeric materials are widely used in drug delivery systems, as they are biologically compatible, and their mechanical properties and their degradation rates can be often tuned and optimized according to the preferred use. For example, one commercially available material is polylactic acid (PLA). Lactic acid is commonly produced via fermentation of dextrose extracted from a starch source, therefore, requires several other processes prior to the synthesis of PLA from lactic acid monomers. Another important characteristic and an advantageous feature of biodegradable polymers is the fact that they can serve as delivery systems for pharmaceuticals, e.g., by providing protection to a drug by preventing its exposure to physiological conditions, or by improving the solubility of a poorly-soluble or insoluble drug, and thus, at times, increase the drug's bioavailability. These abovementioned advantageous properties promote a safe and improved medical treatment and patient compliance, and therefore are sought after in the pharmaceutical industry. In this regard, modified polysaccharides, e.g. starches and alginates, are an appealing option. For example, U.S. Pat. No. 5,846,530 discloses chemically cross-linkable alginates. A further U.S. Pat. No. 6,313,105 discloses a thermoplastic mixture of natural and “dialdehyde starch”, i.e. starch oxidized to aldehyde groups. The U.S. Pat. No. 6,790,840 discloses reversibly crosslinked hydrogels, such as alginates. Also, the U.S. Pat. No. 7,255,732 compositions obtainable by thermomechanical gelatinization of starch with dialdehyde starch. Additionally, native starch was reported for the preparation of nanoparticles containing the active agent curcumin, in Suk Fin Chin et al, International Journal of Polymer Science, Volume 2014, Article ID 340121, with the digital object identified number doi:10.1155/2014/340121. Thus, there is a need in the art to provide a both time and resources efficient methodology, to obtain a biodegradable material having compatible proprieties to serve in the above-described systems. SUMMARY OF THE INVENTION Provided herein is a composition of matter comprising a polysaccharide chemically crosslinked by an aromatic dialdehyde. The aromatic dialdehyde may usually be selected from the group consisting of divanillin, di-cinnamaldehyde, di-coniferylaldehyde, di-coumaraldehyde, and di-sinapaldehyde. Preferably, the polysaccharide is a starch, an alginic acid, or hydroxypropyl cellulose. In currently preferred embodiments, the polysaccharide is a starch, and the aromatic dialdehyde is divanillin. The composition may be present in a form of a polymeric sheet, or a polymeric particle/capsule. In a further aspect provided a pharmaceutically acceptable formulation comprising the composition of a polysaccharide chemically crosslinked by an aromatic dialdehyde. Preferably, the formulation is in form of nano-sized particles. The formulation usually comprises a bioactive material. The bioactive material may preferably be a naturally occurring substance, an antibiotic, or a CNS-active drug, e.g. curcumin or a cannabinoid, such as cannabidiol, an antiemetic, such as granisetron, or a peptide or polypeptide, such as insulin, or glycoprotein, oligonucleotide, antibody drug conjugate, or peptide drug conjugate. The composition, particularly nano-sized particles, may further comprise a lipid and/or a surfactant and/or a cosolvent, e.g. those as may be used in the preparation of the nano-sized particles. Preferably, these lipid and/or a surfactant and/or a cosolvent are selected from the group consisting of caprylocaproyl polyoxyl-8 glyceride, polyoxyl-40 hydrogenated castor oil, propylene carbonate, tetraglycol, glyceryl oleate and dioleate, isopropyl palmitate, and cocoa butter. In a further aspect provided herein a process of manufacturing of a polymeric composit