Ocular Drug Delivery Final 712y1f
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OCULAR DRUG DELIVERY
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6
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INTRODUCTION ÿÿ %%# % ! &&'ÿÿ "% | %( $$ $%%() * "$$' ( +% ()&"$$' | % % +% ! ! ! ,( ,$! (% # ,("$,!-(, ( |
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ANATOMY ! 7( ( $$ %%$, ,,$",9 (,$ $ ! $(!(%$%%$!
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ŒACTORS ATTRIBUTING POOR BIOAVAILABILITY
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NUTRIENT TRANSPORTERS AND EŒŒLUX PUMPS IN THE EYE %( $$ $$ +% # % % ( " ( % ( # ##( $$ " ( $
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VITAMIN C TRANSPORTER
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EŒŒLUX TRANSPORTERS 6% "$$ -% 56%$ % ,5- $ 7"!- " " 6 5"6($% ,-((% $-5 $ 7"! " 7" 6 $% (-(( ($% % ( 6% # $#$# +% " !$!( % # $,$%, ! "$% + " |
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BLOOD-OCULAR BARRIERS ( % ( + "( "$ " "$7$" ( " (# -%4"$79 " "$7 " ( "$7 " % ( ( $$ $$ ( # (" % # ( %$$"( 9 (,$$( (%($!%$ ( 9 ( $%( !(" !( $ !"( (" ,( % "$(" %$( ( % " " - "$ % $%! %( $5 |6( !(-$$ $ %$$ |
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DISEASES
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DRUG DELIVERY
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NDDS PRO-DRUG ŒORMULATIONS AND PERMEABILITY ENHANCERS . $%%($ # ## #! #%% $: $"$,"$,% "$ # $+%%(# " ! OCULAR ENZYMES | , ,: , &=7 (+$ DRUGS /$# 5$# $$ "< " !"$ # 6 $# *7$ ,%! *7$$, "<#$ %$ $$!( # ! 8 |
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#$ %% &''('&$ )* '(( + # + $,$- - % )
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PERMEATION ENHANCERS $% ( ! " ( # -(( % "$ ( ( ! $5# $ , ?6 EXAMPLES ,"$ ,( $!! (# $$"
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INJECTABLE THERAPIES INTRA-VITREAL INJECTION < !$ $# !> / $
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$ ( , %(($ # $ ( (! | " $$ $$-!# $ < DRUGS ΠV -(( $ !$# % -( ,-( "$!%%# # $ < 53/6B% ("("3/7 ,((
M N A 2006 f L Π2006
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PERIOCULAR ROUTES $ "<#$, "$",% "$",, % <+$ $5/( $( , &6
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PARTICULATE DRUG DELIVERY SYSTEMS N M %$ 5,6%$ 5 ,D6 ( !8 %( %( %$ %$ 5! $ ,
&6 1%$ $: # 7# $ < %$ ,( ( (, %$ $8 $ $$( % ! |
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!$!$ ( $!$ ,% ,$$ ! , " !# ! -(%( %( $! $# ( ( ( $$$% , % ! !, $$-$!7 $# 0 1|27 |$%$ +E 8 %$ + /7F %(%(( $!$ 5|7 6-( %$ ($ 5|6: | 7 - %$ %$5$ 77 !$$ 6 %( |
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NANOSUSPENSIONS 6$ 5 &6-$ % "! ! 2 &7$ ! %$ % ! ! (!( ( $$ "#$"$ ( !$$-!%(($ %%$
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MICROEMULSIONS (,($%( $ $77 - !%$% ! $ (,%%$ !$$,|/ ' ,%%$ ( $%( ( " ! ,-((!( ""$ $ $$ $ -$ 7 (+ ($ ($ 5 1 6! $-((- $ %( ! $ $,(!($$%%($ !-(9 $"$ &D!'2 -$ $ -(($($!!( -( + $$ "$$ "$ |
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LIPOSOMES 2% ,% %$ %$ , # $$% !!" - * - ( $$- %$- # ! $ $ (% ,$ , # %$" < $9! 5 ÿ7 >7!! $ 6 ( %# # -"!$-! $ $# $ %
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NIOSOMES 6$% $ ,$$ $ ( ! % % $!! ( $"#$"$ $$ 5("%$6 $$$ +(" ! |$- ! ""% $$$
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DISCOMES 2! -(8 ! B&D # "%!$$6 " (( |
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OCULAR IMPLANTS #! $# !( % $ # $! $ ( $ %$$- $$" $-+$ # $, (!( ( ! ( ( # -( "<#$%$ 7 ! ,-( # $ %($ ( %$$ % 7 ! $ $%$" ( |
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BIODEGRADABLE AND NON- BIODEGRADABLE IMPLANTS " !"$ %$(# ( #! ,$$ $ !!% $$ $!% 5 6( #! #$' %$ -( ( ! %$
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MUCO ADHESIVE POLYMERS
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6
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INTRODUCTION ÿÿ %%# % ! &&'ÿÿ "% | %( $$ $%%() * "$$' ( +% ()&"$$' | % % +% ! ! ! ,( ,$! (% # ,("$,!-(, ( |
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ANATOMY ! 7( ( $$ %%$, ,,$",9 (,$ $ ! $(!(%$%%$!
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NUTRIENT TRANSPORTERS AND EŒŒLUX PUMPS IN THE EYE %( $$ $$ +% # % % ( " ( % ( # ##( $$ " ( $
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VITAMIN C TRANSPORTER
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EŒŒLUX TRANSPORTERS 6% "$$ -% 56%$ % ,5- $ 7"!- " " 6 5"6($% ,-((% $-5 $ 7"! " 7" 6 $% (-(( ($% % ( 6% # $#$# +% " !$!( % # $,$%, ! "$% + " |
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DISEASES
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DRUG DELIVERY
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NDDS PRO-DRUG ŒORMULATIONS AND PERMEABILITY ENHANCERS . $%%($ # ## #! #%% $: $"$,"$,% "$ # $+%%(# " ! OCULAR ENZYMES | , ,: , &=7 (+$ DRUGS /$# 5$# $$ "< " !"$ # 6 $# *7$ ,%! *7$$, "<#$ %$ $$!( # ! 8 |
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INJECTABLE THERAPIES INTRA-VITREAL INJECTION < !$ $# !> / $
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PERIOCULAR ROUTES $ "<#$, "$",% "$",, % <+$ $5/( $( , &6
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!$!$ ( $!$ ,% ,$$ ! , " !# ! -(%( %( $! $# ( ( ( $$$% , % ! !, $$-$!7 $# 0 1|27 |$%$ +E 8 %$ + /7F %(%(( $!$ 5|7 6-( %$ ($ 5|6: | 7 - %$ %$5$ 77 !$$ 6 %( |
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/ $ $ %$5$ 77!$$ 6 %( ( %$$ $# % % !#-((!(%$! # .6#$ 5-$6-( % 9 $( ! ( $ # $% (3/%$5,27 $ B7!$$ 65|2/6%( (%# $$ $# % $ # $% -%(($ $# , %$% $ % 5! $$"6 %( " $"#$"$ |
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NANOSUSPENSIONS 6$ 5 &6-$ % "! ! 2 &7$ ! %$ % ! ! (!( ( $$ "#$"$ ( !$$-!%(($ %%$
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MICROEMULSIONS (,($%( $ $77 - !%$% ! $ (,%%$ !$$,|/ ' ,%%$ ( $%( ( " ! ,-((!( ""$ $ $$ $ -$ 7 (+ ($ ($ 5 1 6! $-((- $ %( ! $ $,(!($$%%($ !-(9 $"$ &D!'2 -$ $ -(($($!!( -( + $$ "$$ "$ |
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LIPOSOMES 2% ,% %$ %$ , # $$% !!" - * - ( $$- %$- # ! $ $ (% ,$ , # %$" < $9! 5 ÿ7 >7!! $ 6 ( %# # -"!$-! $ $# $ %
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( #! $% ( %$ !%% " $ +," $$ ! -($ $%$ %$ ,(- # , $% $%# $ ( ,( $!7 $%$< ( :-5 , ÿ6
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NIOSOMES 6$% $ ,$$ $ ( ! % % $!! ( $"#$"$ $$ 5("%$6 $$$ +(" ! |$- ! ""% $$$
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DISCOMES 2! -(8 ! B&D # "%!$$6 " (( |
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1 ( ,%( $,$ $ ( ( $: "(! $ , -((% 9 %% 5$#$ ,!$"$( - $$ $ $- !(6(: ( -$! $# , % $$$ $$ %# # # ($ $! $# |
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3 # $% %$5 65| 1 16 $$ $! $# %$% % #: ! |$ 5| 1 16 G 7$"$ % 1 $(# (# % $!7 ( $%%($7 $# 7#$ ( $$!-(53/6 $!$ 5 76( (" $ 7 ($ #$85636
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OCULAR IMPLANTS #! $# !( % $ # $! $ ( $ %$$- $$" $-+$ # $, (!( ( ! ( ( # -( "<#$%$ 7 ! ,-( # $ %($ ( %$$ % 7 ! $ $%$" ( |
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BIODEGRADABLE AND NON- BIODEGRADABLE IMPLANTS " !"$ %$(# ( #! ,$$ $ !!% $$ $!% 5 6( #! #$' %$ -( ( ! %$
!"$ %$(# ( #! " ! "$ " ( (% ,( "$ < % ,( 9 #$,( ( ($7$ ( !5 , ÿ6 |
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IONTOPHORESIS $ %%$ ( !% ( !%%$ -( $ !( (! ( !,( ! $ ,-(( ( %% (! ,%$ $ -( ( " %$ ( ( ! # ( ( (!( (
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$$ $%( (# " -(# %(($!$! $!$ ,$, $ #$"$ ( %( (( #! " !## , ( ,#( :!$%$ # $< " !($7 $ $ (# (-($ $%( " $# ( % $ # $"# % ( ( (,-((" #"$ $ ## $ # $# !7 |
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|('% !%" $$#$"$ %( !%%$% # $ $ %( $$
(! $%""( !$ $$$ +"$ - ( # $ ( $$ ( !%( -(!$ $ % ( %%$%$ ( $ ( ( $- $ | $$$ (#$ (# (-(( |( - $$$ # - ! "(%# !# %$ % %(($(! |
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I $!,$ # ! ( %"$ $ $%( "" !$ - ' ( # ! %( $ %%+ $&7$ $ (% %# $
$# $$$!- $# $$,!% $$$ $# ( ,-(( $ $%(
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6$$
$ ,?ÿ7H
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/ E4 ù $ ( !% ! 9 ù %$ 7 % ù "$ -(# ( % ù $% % !%
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( /$8 $ ,-(( $ $8 - % ( (+ ( 9 %% $(! !$ $ "( ! ,( !%$ %$ " !% ( ! (+ (
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MUCO ADHESIVE POLYMERS
|$ 6(! 1( # % |$5$6 $8 @@@ 6" 5 $8 6 @@@ $ @@@ 6(6@@ "+ ($ $$$ @@5@6 $! @@ | @@5@6 0! @ 0$!$ @ $ !$ @ |$+ @5@6
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HYDROGEL OR INSITU GELLING SYSTEM 6" !$$! ( $7 7-( !"#$"$ ( %(($(! $$" $ # ( #( %% %$,! $$! %# "#$"$ ( " ( "%%$$%%$ %(($ ! %$! $$!! $ $$$ ## , %$#$$($,($"
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! $ %!$! $# ( # $%% ( $9-( ( !! $ $% $%($'( $(! 5 +%$ % , % ,% 6( # I( $7 7 ( $%% (! $ $ ! $ !$! ! $( (%#!( $#$"$! % $
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Õ $ # $% ( # ! $$! ( # %(($! $# !%$+ $!"%$ ( %"%$>? |$ ( % %$" (#"$ ( ( ( # !$ ( ! $ # % H( A $ $ # $% %$ ÿ" $$$$ 516 (! $"#$"$ ##(- (( $"#$"$1, $""", " * ?$ | ÿ! $$% -( *;1 9 $ |
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( + >;"%$?;%$$(- ! ( ! $ !(( %($!$ ( %$% $ - + %&("! ( 18: $ - # $% ( # "$ ! $ "9 $ 8 ! +$!$ %$( $ # ($ ( $ $# %$% (($ /!%$+ ( ($! $$! %(($! $# %$+- % " 6( $ + $ # ! # $( # %$ 5%$ 7 %%$$ 6B(5||
7 66 ( # ! $!%% % $$8 $! $# $$$ # % ( |
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| $ # $% ( ! $$! ("! # $! ( $ (- + %H( 1 #-$ ( % $ ("!! $$ !% " $J *K | $ # $% %(($ !$+ !$! 5A $E6"-( |16 5 ( $*236-(( # (! ! ##% $ (( $! ' |16$ ( ! " (( $! |16$ J &K
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( % !! ! $" $! I $+%(($ $# - # $% " # $ |$$56"%$E"(!(- $$! % $ % ( !$ ( %$ (-(( $ J HK 2 $$! % ( ! $$! ! ($5(+ ($6 $$$ (! $ !$-$$$$ J K
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|$7 ÿ7!7%$5$6%$ " ! $$!# ($ -(# %$! % $ %# $ "#$"$ ( (( ! $ $'%$$ %$ $ $77! $ %$+(($ - % % "$8!( %( %% (+$%%$ ($ $$$ A*1"%$>? 2 $ # $% ! ' |16" $!! $# !$+J> K |
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16
2
2 %) # # ) # #2-#1 ) # + -$2 #$22 ) #- # - )2
) # ##
%) 1 % $22 #12 % # + 1%) *-1- - -2 + 2#% 1 ) #1 # - # %#1#2* ))
%- #2* % ) -2 - 2) # #2#1 ))
%* )
+ - ) #) +*) # ) # - 2 |
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" 234 % - % # )131 + # 5) -)- % - % 67
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" * 2 +#2) % 21 #1 #2* 1*# )#- 1# # 4-)-) 2 2 -|%8. $ # #2*#2)-)- ) # *# + #- 98 # # #2) #2 #- :4- * % - #4-)-) + %-*#
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*$ #)#+*#$ )4-)-- 2 *2 2 # 1 % 4 2 2%#1 - * #2)4-)-# #)
-- # - 2# )-
#) # 4 + +; # )-* - - #
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| #1#2* * ##2 +** )- )) 4)4- # - % 1 # #% %%)2 #1#2* - % 8 - );- 2
# #2*#2)- # -#1 -* #) + )2 %- %-#2) #-* - #2) ) + %- % # # ) # 1-&<$&=> 1 # 2# )# ) 1 1%) *- )) )4 % #- )+% % #* # # ) |
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) )- ) ) #1#2*#2)4 # ) &,?<''(,&@,( - #2 1 %% +) % #)1 8# # %%)#1#2* *
- 2 #*+ 8#% #2* ##2* %+ )2) #
- #2)) # #1 2 )-# %+)-);$ 2 2#) - #)#- 1--* +* %
1) ) - ) %1 ##1 + #2##)* -* # )- )
- 2)* %-) #2#1 -*4-#2) ) #+* * #
1-#1 2 - ) 1 # 2
- 2 -)-) # )-);2 2 -) # #1 - ) ) - 2 # 2 +* ## 1+* ) # %- 2 4-#1 2 %#+*)1- 2 - *1# # *1- *1 - 2 |
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CASE STUDY !" """"# |! !"A 4 "<''=4,B4<
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||C 2 1 -%%) # %* % +8 ; )- #
) #1#2*- ++ %) ) # |C - $<&$- - :C 8 ; )- # C ) - )* #
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:) #) ) % |-2 # $)- #) #--) | #)#- 9 - -2 #*4 :## ) - ) +* % | - $)- #4 : 1%) *) # ) ) %$<'+## ) - % $D' - ## % :## ) ) ) % $<' $D'-2 + ) ) + 2#- ) -* 1) - 1) %- ## % : |
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1- ) 1 - %- %) ) # % $ %& '( $%& )*+*, ,+-*./+'$ |
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L - A - B f
f f
f 005% BAK A N B j f O f A 2000 B 5000 |
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CONCLUSIONS ( $( ( A%# ( $% !$ $! $# -(%!+
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6 %*2 % ) #1#2*% C )-9 # )) ) # 06 2 /6 | 2 /,>&4?7& , H )- ) #1#2* * | , ,H7?*
1#2* *C ) %) ) E"< <'&'&<$<&
) )- ) ) #1#2*#2) &,?<''(,&@,( |
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| * % #2* %| # |# CF| | "A <''G4?4,'$ ,( #1#2*C )- % + - )) EA4 |$E<'&'4<<C??B$?,D * )#2* % 2 - )$% ) #2)E|! 3 2.1H&,. ,|&?B&@&?B,4 &GGD |
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- 1 # + ) % ) - ) ;) ##1#2*4 "F=( <''B&&"!
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