Sustained timolol maleate delivery from liposomes for glaucoma therapy and occular hypertension
OwnerSubramanian Venkatraman, Yin Chiang Freddy Boey +1inventors
InventorsSubramanian Venkatraman, Yin Chiang Freddy Boey, Jayaganesh V. Natarajan
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Abstract
Various embodiments relate to the field of liposomal formulations for drug delivery, in particular, liposomal formulations for ocular drug delivery. More specifically, various embodiments relate to sustained timolol maleate delivery from liposomes for glaucoma therapy and ocular hypertension.
Claims33
Liposomal formulation for ocular drug delivery, comprising:
- liposomes each comprising a core surrounded by one or more lipid bilayers, and timolol maleate comprised in the core of each liposome,
- (a) wherein one or more of the lipid bilayers are comprised of a mixture of 50-80 mol % of a lipid and 20-50 mol % of a steroid alcohol, wherein the lipid is comprised of glyceride, phosphatidylcholine, and/or sphingolipid;
- or
- (b) wherein the one or more lipid bilayers are comprised of a mixture of 50-80 mol % of a neutral lipid and 20-50 mol % of a charged lipid, wherein the neutral lipid and the charged lipid are comprised of glyceride, phosphatidylcholine, and/or sphingolipid.
Liposomal formulation according to any one of the preceding claims, wherein the lipid and/or the neutral lipid comprises one of phosphatidylcholine and sphingolipids.
Liposomal formulation according to any one of the preceding claims, wherein each liposome comprises 0.67-1.5 mg/ml of entrapped timolol maleate concentration based on an initial timolol maleate concentration of 2 mg/ml.
Liposomal formulation according to any one of the preceding claims, wherein timolol maleate is comprised in the core and another ocular drug is comprised in the lipid bilayer of each liposome.
Liposomal formulation according to any one of the preceding claims, further comprising:
- additional liposomes each comprising a core surrounded by one or more lipid bilayers;
- and
- another ocular drug different from timolol maleate comprised in the one or more lipid bilayers of each additional liposome.
Liposomal formulation according to any one of the preceding claims, wherein the liposomal formulation comprises a timolol maleate to lipid mole ratio of about 0.01 to about 0.30, preferably 0.01, 0.05, 0.10, 0.15, 0.20, 0.25, or 0.30.
Method of preparing a liposomal formulation comprising liposomes each comprising a core surrounded by one or more lipid bilayers, and timolol maleate comprised in the core of each liposome, wherein the one or more lipid bilayers are comprised of a mixture of 50-80 mol % of a lipid and 20-50 mol % of a steroid alcohol, wherein the lipid is comprised of glyceride, phosphatidylcholine, and/or sphingolipid, the method comprising:
- mixing the lipid with the steroid alcohol in an organic phase;
- evaporating the organic phase mixture to obtain a thin film of the lipid and steroid alcohol;
- hydrating the thin film with ammonium sulfate solution to form vesicles;
- suspending the vesicles in a salt solution;
- adding a drug solution to the suspension;
- and
- incubating the suspension containing the vesicles and drug solution.
Method of preparing a liposomal formulation comprising liposomes each comprising a core surrounded by one or more lipid bilayers, and timolol maleate comprised in the core of each liposome, wherein the one or more lipid bilayers are comprised of a mixture of 50-80 mol % of a neutral lipid and 20-50 mol % of a charged lipid, wherein the neutral lipid and the charged lipid are comprised of glyceride, phosphatidylcholine, and/or sphingolipid, the method comprising:
- mixing the neutral lipid and the charged lipid in an organic phase;
- evaporating the organic phase mixture to obtain a thin film;
- hydrating the thin film with ammonium sulfate solution to form vesicles;
- suspending the vesicles in a salt solution;
- adding a drug solution to the suspension;
- and
- incubating the suspension containing the vesicles and drug solution.
Dependencies are inferred from the claim text.