Therapeutic potential of cellulose-cyclodextrin-curcumin nanocrystals in the treatment of peripheral neuropathies
Disclosed is a complex including: cellulose nanocrystals; at least one β-cyclodextrin molecule; and at least one curcumin molecule, suitable for use in the treatment of any kind of peripheral neuropathies. Further disclosed is a pharmaceutical composition including at least the complex and at least one pharmaceutically acceptable excipient. Also disclosed is the use of the complex or the pharmaceutical composition, in particular in the form of a hydrogel, a subcutaneous implant, an implantable pump, an implanted biofunctionalized nerve conduit, to improve the treatment compliance, to allow an extended release of the complex and to obtain better pharmacokinetics.
1 . A method for treatment of a peripheral demyelinating neuropathy, comprising administering by injection to a subject in need thereof an effective dose of a complex comprising:
cellulose nanocrystals;
at least one β-cyclodextrin molecule; and
at least one curcumin molecule,
wherein the cellulose nanocrystals are loaded with β-cyclodextrin on their surfaces, and curcumin is included within β-cyclodextrin cavities on the cellulose nanocrystals, thereby forming a curcumin-β-cyclodextrin-cellulose nanocrystal complex, and
administered at a curcumin equivalent dose of 0.2 mg/kg/day.
2 . The method of claim 1 , wherein the complex is administered in the form of a composition comprising the complex and at least one pharmaceutically acceptable excipient.
3 . The method of claim 2 , wherein the composition is in the form of a hydrogel.
4 . The method of claim 2 , wherein the composition is administered by injection by way of a subcutaneous, intramuscular, intravenous or perineural route.
5 . The method of claim 2 , wherein the peripheral demyelinating neuropathy is Charcot-Marie-Tooth disease.
6 . The method of claim 2 , wherein the peripheral demyelinating neuropathy is Charcot-Marie-Tooth disease type 1A.
7 . The method of claim 2 , wherein the peripheral demyelinating neuropathy is related to a traumatic injury.
8 . A method for treatment of a peripheral demyelinating neuropathy, comprising administering by injection to a subject in need thereof an injectable pharmaceutical composition comprising a complex of cellulose nanocrystals, β-cyclodextrin, and curcumin,
wherein the cellulose nanocrystals are loaded with β-cyclodextrin on their surfaces and curcumin is included within hydrophobic cavities of the β-cyclodextrin on the cellulose nanocrystals, thereby forming a curcumin-β-cyclodextrin-cellulose nanocrystal complex,
and wherein the complex is administered at a curcumin-equivalent dose of 0.2 mg/kg/day by a route selected from subcutaneous, intramuscular, intravenous, or perineural injection, thereby improving motor nerve conduction velocity (MNCV) in the subject.
9 . A method for treatment of Charcot-Marie-Tooth disease type 1A (CMT1A), comprising administering by injection to a subject in need thereof, an injectable pharmaceutical composition comprising a complex of cellulose nanocrystals, β-cyclodextrin, and curcumin,
wherein the cellulose nanocrystals are loaded with β-cyclodextrin on their surfaces and curcumin is included within hydrophobic cavities of the β-cyclodextrin on the cellulose nanocrystals, thereby forming a curcumin-β-cyclodextrin-cellulose nanocrystal complex,
and wherein the complex is administered at a curcumin-equivalent dose of 0.2 mg/kg/day, thereby maintaining measurable plasma curcumin at 8-12 hours post-dose and improving MNCV as assessed by electrophysiology.