J Appl Oral Sci. 420
Edit orial
http://dx.doi.org/10.1590/1678-77572016ed0032016;24(5):420-2
Sust ained dr ug- deliver y sy st em : a pr om ising t herapy for
dent ure st om at it is?
Dear Readers,
Dent ure- induced st om at it is is t he m ost com m on t y pe of or al can didosis an d t h e m ost f r equ en t m ucosal alt erat ion associat ed w it h com plet e or rem ovable part ial dent ures in t he elderly. Despit e b ei n g a n i n f ect i o n o f m u l t i f a ct o r i a l et i o l o g y, t his condit ion has as m ain et iological fact or t he colonizat ion of dent ure- bearing m ucosa and acrylic bases by species of Candida spp., especially Candida albicans, found in 50 t o 98% of all cases25.
Different t reat m ent s are indicat ed for dent ure st om at it is, including t opical ant ifungal and syst em ic t herapy, care w it h oral hygiene, dent ure cleaning and disinfect ion pr ocedur es, r eplacem ent of old dent ur es, elim inat ion of anat om ic ir r egular it ies, re- est ablishm ent of at raum at ic occlusion, rem oving t he dent ure at night and nut rit ional rest it ut ion12.
Alt hough syst em ic ant ifungal t herapy is suggest ed for im m unosuppressed pat ient s, t hese drugs m ay p r esen t p ot en t ial h ep at ot ox ic an d n ep h r ot ox ic ef f ect s an d in t er act ion w it h ot h er d r u g s, t h u s incr easing t he adver se sy st em ic effect s6. Topical
an t if u n g al ag en t s as n y st at in an d m icon azole ar e lar gely u sed f or t h e t r eat m en t of den t u r e st om at it is12,15.These ant ifungal drugs are effect ive
in r eliev ing t he clinical signs and sy m pt om s of dent ure st om at it is associat ed w it h Candida spp.; however, t hey cannot reach a t herapeut ic ant ifungal con cen t r at ion on t h e in n er den t u r e su r f aces1 5.
Con seq u en t ly, r e- in f ect ion of t h e t r eat ed or al m ucosa m ay occur aft er convent ional t herapy w it h t opical and sy st em ic ant ifungal dr ugs. The high rat es of clinical r elapse and r ecur r ence in up t o t w o w eeks post - t reat m ent m ake t he t reat m ent of dent ure st om at it is challenging15,18.
Factors other than inability to m aintain therapeutic concent rat ions of ant ifungal drugs on t he surface of dent ures are associat ed wit h failure of convent ional an t if u n g al t h er ap y in clu d in g t h e f ollow in g : 1 )
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sw allow ing, and t ongue m ovem ent s; 2) lack of pat ient com pliance t o ant ifungal t herapy due t o cost s required for t he m edicat ions, unpleasant t ast e of t opical agent s, cont inuous ut ilizat ion of dent ures an d st r ict dr u g r egim en ; 3 ) per sist en t con t act bet ween inj ured m ucosa and cont am inat ed int ernal dent ure surfaces, w hich favors re- infect ion of t he m ucosa and causes t raum a t o support ing t issues, ext ending t he clinical course of t he pat hology20,21.
An effect iv e t r eat m ent of dent ur e st om at it is
requires a t herapy based on t he sust ained release of an t if u n g al d r u g s t h at m ay r each ad eq u at e
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t h e Can d id a f r om b ot h t h e su p p or t in g t issu es and infect ed dent ur e sur faces. I n t his cont ex t , incor porat ion of ant ifungal/ ant im icr obial agent s int o dent ur e base m at er ials t o be pr ogr essively released t o t he oral cavit y has been suggest ed t o
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colonizat ion, and cont r ibut e t o t he t r eat m ent of dent ure st om at it is5,20,21. This prot ocol requires only
t he use of dent ures by pat ient s, t hus reducing t he need for pat ient com pliance t o ant ifungal dr ug regim ens21. Furt herm ore, t he incorporat ion of drugs
int o dent ure liners breaks t he cont act bet w een t he
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cycle of re- infect ion via prost heses14. I n t his regard,
t he use soft lining m at erials is highly recom m ended as it result s in t he recovery of inj ured t issues and pat ient com fort14. How ever, soft lining m at erials,
m ainly short - t erm ones as t issue condit ioners and t em porary resilient liners are easily degradable and suscept ible t o m icrobial colonizat ion17. Therefore,
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ant im icr obial agent s also has t he advant age of increasing t heir clinical longevit y. As life cycle of shor t - t er m soft liner s is appr oxim at ely 14 days, t he t reat m ent period of dent ure- induced st om at it is
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t o t he period required w hen convent ional t opical ant ifungal agent s are used20,21. As a result , dent ure
st om at it is can be t reat ed before replacing t em porary soft liners w it h long- t erm liners or fabricat ing new dent ures, in a relat ively short period.
Although incorporation of antifungal/ antim icrobial agent s at com m ercially available concent rat ions t o polym eric/ plast ic m at erials can effect ively inhibit t he grow t h of C. albicans20,21,it m ay affect t heir
m or phological st r uct ure24 and propert ies such as
t ensile st rengt h1,22,wat er absorpt ion7,m odulus of
elast icit y and weight1,hardness1,20,23, roughness23,
and peel bond st rengt h t o dent ure base resin2. I n
an order t o provide low er concent rat ions of drugs t o t hese m at erials w it hout severely com prom ising t h e i r p r o p e r t i e s, Bu e n o , e t a l .5 d e t e r m i n e d
m inim um inhibit or y concent rat ions ( MI Cs) of C. albicansELR¿OPIRUDQWLIXQJDODQWLPLFURELDODJHQWV
added t o a t em porary resilient liner and a t issue
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k et ocon azole, it r acon azole, an d ch lor h ex id in e
Karin Hermana Neppelenbroek
J Appl Oral Sci. 421 2016;24(5):420-2
diacet at e) in cor por at ed at MI Cs in t o bot h sof t m at erials w ere effect ive in inhibit ing t he grow t h of
C. albicans for up t o 14 days.
Consider ing t he pr om ising r esult s of Bueno, et al.5, som e st udies w ere perform ed t o evaluat e
t he effect s of drug addit ion at MI Cs on im port ant propert ies of t hese m at erials. Wit h t he except ion of it raconazole, t he MI Cs of drugs incorporat ed int o t em porary soft lining m at erials result ed in m inim al changes in t heir peel bond st rengt h t o a dent ure base resin wit hin 14 days19.Aft er 14 days, t he MI Cs
of ny st at in and k et oconazole in bot h m at er ials and chlorhexidine in t em porary resilient liner did
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The solubilit y of bot h resilient m at erials was not m od if ied b y n y st at in at MI C w it h in 1 4 d ay s1 0.
Also, in t his issue, Lim a, et al.11 observed t hat t he
addit ion of drugs at MI Cs result ed in no harm ful effect s for t he porosit y of bot h soft lining m at erials in different periods of wat er im m ersion, except for chlorhexidine and nyst at in in t he t issue condit ioner and chlorhexidine in t he t em porary resilient liner at 14 days. Despit e t hese favorable out com es, before t he incorporat ion of drugs at MI Cs m ay be indicat ed as an alt ernat ive t herapy for dent ure st om at it is, it is necessary t o evaluat e t he biocom pat ibilit y of t his prot ocol w it h t he oral t issues. During t heir life cycle, polym eric/ plast ic m at erials release soluble subst ances in t he oral environm ent , w hich m ay be pot ent ially t oxic, such as m et hyl m et hacrylat e and dibut yl pht halat e. When released in saliva, t hese com ponent s m ay even act at sit es dist ant fr om t he area cont act ing t he m at erial9,16.These possible
cyt ot oxic effect s have been assessed in vit ro by
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r est r ict ed, since t he effect s of t est s per for m ed direct ly on cells are m ore m arked t han t he oral condit ions in vivo. I n addit ion, t he lim it ed lit erat ure available on t he in vivo biocom pat ibilit y of dent ure base lin er s w it h or al t issu es in an im al m odels sh ow ed an in cr eased t h ick n ess of t h e st r at u m corneum layer for rat s receiving acrylic int raoral
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m at erial3,4.Nevert heless, t here is lack of inform at ion
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liners w it h oral t issues in anim al m odels.
From t he in vit ro st udies evaluat ed, it is possible
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r esilien t m at er ials b y an t if u n g al/ an t im icr ob ial agent s, especially in low er concent rat ions, m ay represent a viable prot ocol for in vivo t reat m ent of dent ure st om at it is during a period sim ilar t o t he convent ional t herapy w it h t opical ant ifungals ( 14 days) . How ever, it is im port ant t o em phasize t hat w hen in t he m out h, dent ure resilient liners m ay be subj ect ed t o addit ional t herm al st ress, pH range, and occlusal load, which could lead t o ot her pat t ern of propert ies of t hese product s. This m ight explain
t he evidence t hat t he m agnit ude and speed of all changes in m at erial propert ies aft er im m ersion in dist illed wat er ( as done in all in vit ro st udies on t he
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t hose observed in clinical condit ion13.Nevert heless,
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t h ese f act or s af f ect t h e ev alu at ed p r op er t ies. Moreover, t he loss of leachable com ponent s is fast er w hen t he soft liner is in t he m out h due t o t he oral environm ent , food, and cleaning m et hods adopt ed by t he pat ient13.
Considering t he aspect s described previously, before clinical indicat ion of t his prot ocol for dent ure st om at it is t r eat m ent , fut ur e in v it r o st udies ar e necessar y t o evaluat e ot her r elevant pr oper t ies
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and dr ug pat t er n of incor porat ion. Fur t her m or e,
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resilient liners should not be considered enough for clinical indicat ion of a m at erial or t reat m ent , since im port ant fact ors as rem oval and hygiene of t he appliances and deform at ion due t o occlusal load in norm al feeding condit ions w ere not analyzed. Thus, aft er observat ions of in vit ro st udies on ot her
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st udies on anim al m odels t est ing t his pr ot ocol, clinical t rials in hum ans are necessary t o allow t he safe indicat ion of drug incorporat ion in t em porary resilient liners as opt im al ant ifungal delivery for dent ure st om at it is t reat m ent .
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