Encapsulation of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
A composition for delivering at least one Non-Steroidal Anti-Inflammatory Drug (NSAID) to a subject, the composition including biodegradable nanospheres, wherein the biodegradable nanospheres include the NSAID dispersed in a biodegradable polymer.
1 . A composition comprising at least one Non-Steroidal Anti-Inflammatory Drug (NSAID) encapsulated in biodegradable polymeric nanospheres, wherein the biodegradable polymeric nanospheres include a polymer selected from
(1) a poly (ester amide urea) wherein at least one diol, at least one diacid, and at least one amino acid are linked together through an ester bond, an amide bond, and a urea bond,
(2) a poly (ester urethane urea) wherein at least one diol and at least one amino acid are linked together through an ester bond, a urethane bond, and a urea bond,
(3) a poly (ester amide urethane urea) wherein at least one diol, at least one diacid, and at least one amino acid are linked together through an ester bond, an amide bond, a urethane bond, and a urea bond,
(4) a poly (ester amide urethane) wherein at least one diol, at least one diacid, and at least one amino acid are linked together through an ester bond, an amide bond, and a urethane bond,
(5) a poly (ester urea) wherein at least one diol and at least one amino acid are linked together through an ester bond and a urea bond, and
(6) a poly (ester urethane) wherein at least one diol and at least one amino acid are linked together through an ester bond and a urethane bond,
further wherein
the at least one diol is a compound of formula:
HO—R 1 —OH, R 1 is chosen from C 2 -C 12 alkylene optionally interrupted by at least one oxygen, C 3 -C 8 cycloalkylene, C 3 -C 10 cycloalkylalkylene,
the at least one diacid is a compound of formula:
HO—(CO)—R 3 —(CO)—OH,R 3 is C 2 -C 12 alkylene,
the at least one amino acid is chosen from naturally occurring amino acids and non-naturally occurring amino acid.
2 . The composition as defined in claim 1 , wherein the polymer is a poly (ester amide urea) (PEAU) comprising the following two blocks with random distribution thereof:
wherein
the ratio of l:m ranges from 0.05:0.95 to 0.95:0.05, l+m=1,
R 1 is chosen from C 2 -C 12 alkylenes optionally interrupted by at least one oxygen, C 3 -C 8 cycloalkylenes, C 3 -C 10 cycloalkylalkylenes,
R 3 is C 2 -C 12 alkylene,
R 2 and R 4 are independently chosen from the side chains of L- and D-amino acids so that the carbon to which R 2 or R 4 is attached has L or D chirality.
3 . The composition as defined in claim 2 , wherein R 1 is —(CH 2 ) 6 —, R 3 is —(CH 2 ) 8 —, and both R 2 and R 4 are the side chain of L-leucine.
4 . The composition as defined in claim 1 , further comprising a permeation enhancer.
5 . The composition as defined in claim 1 , wherein the composition is for administration across at least one of dermal and epidermal barriers, and wherein the nanospheres are configured so as to not enter systemic circulation.
6 . The composition as defined in claim 1 , wherein the nanospheres are between 100 nm and 500 nm in diameter.
7 . The composition as defined in claim 1 , wherein the nanospheres have a mean diameter of between 100 and 400 nm.
8 . The composition as defined in claim 1 , wherein the nanospheres have a mean diameter of between 150 and 200 nm.
9 . The composition as defined in claim 1 , wherein the NSAID forms between 5% and 10% w/w of the composition.
10 . The composition as defined in claim 1 , wherein the NSAID is ibuprofen.
11 . The composition as defined in claim 1 , wherein the composition includes a surfactant and a co-surfactant.
12 . The composition as defined in claim 10 , wherein the surfactant is polyvinyl alcohol (PVA) and the co-surfactant is polysorbate 80.
13 . The composition as defined in claim 12 , wherein v/v concentrations of PVA and polysorbate 80 in the composition are respectively between 5% and 15% and between 1% and 4%.
14 . The composition as defined in claim 12 , wherein v/v concentrations of PVA and polysorbate 80 in the composition are respectively between 9% and 11% and between 1.5% and 2.5%.
15 . A method for manufacturing a suspension of nanospheres containing a non-steroidal anti-inflammatory drug (NSAID), the method comprising:
dissolving the NSAID in a hydrophobic phase, wherein the hydrophobic phase includes a polymer dissolved in an organic solvent, the polymer being selected from
(1) a poly (ester amide urea) wherein at least one diol, at least one diacid, and at least one amino acid are linked together through an ester bond, an amide bond, and a urea bond,
(2) a poly (ester urethane urea) wherein at least one diol and at least one amino acid are linked together through an ester bond, a urethane bond, and a urea bond,
(3) a poly (ester amide urethane urea) wherein at least one diol, at least one diacid, and at least one amino acid are linked together through an ester bond, an amide bond, a urethane bond, and a urea bond,
(4) a poly (ester amide urethane) wherein at least one diol, at least one diacid, and at least one amino acid are linked together through an ester bond, an amide bond, and a urethane bond,
(5) a poly (ester urea) wherein at least one diol and at least one amino acid are linked together through an ester bond and a urea bond, and
(6) a poly (ester urethane) wherein at least one diol and at least one amino acid are linked together through an ester bond and a urethane bond,
wherein
the at least one diol is a compound of formula:
HO—R 1 —OH, R 1 is chosen from C 2 -C 12 alkylene optionally interrupted by at least one oxygen, C 3 -C 8 cycloalkylene, C 3 -C 10 cycloalkylalkylene,
the at least one diacid is a compound of formula:
HO—(CO)—R 3 —(CO)—OH,R 3 is C 2 -C 12 alkylene,
the at least one amino acid is chosen from naturally occurring amino acids and non-naturally occurring amino acid;
emulsifying the hydrophobic phase in a hydrophilic phase; and
evaporating the organic solvent.
16 . The method as defined in claim 15 , wherein the hydrophilic phase includes a surfactant and a co-surfactant.
17 . The method as defined in claim 16 , wherein the surfactant is polyvinyl alcohol (PVA) and the co-surfactant is polysorbate 80.
18 . The method as defined in claim 17 , wherein v/v concentrations of PVA and polysorbate 80 in combined hydrophilic and hydrophilic phases are respectively between 5% and 15% and between 1% and 4%.
19 . The method as defined in claim 18 , further comprising adding additional polysorbate 80 after evaporation of the organic solvent.
20 . The method as defined in claim 15 , wherein the solvent is dichloromethane.
21 . The method as defined in claim 15 , wherein the polymer is a poly (ester amide urea) (PEAU) comprising the following two blocks with random distribution thereof:
wherein
the ratio of l:m ranges from 0.05:0.95 to 0.95:0.05, l+m=1, R 1 is —(CH 2 ) 6 —, R 3 is —(CH 2 ) 8 —, and both R 2 and R 4 are the side chain of L-leucine.