Review Article Carrier-Based Drug Delivery System for Treatment of Acne

15 Pages·2014·4.14 MB·English

Hindawi Publishing Corporation
e Scientific World Journal
Volume 2014, Article ID 276260, 14 pages
http://dx.doi.org/10.1155/2014/276260
Review Article
Carrier-Based Drug Delivery System for Treatment of Acne
AmberVyas,AvineshKumarSonker,andBinaGidwani
UniversityInstituteofPharmacy,PanditRavishankarShuklaUniversity,Raipur492010,India
CorrespondenceshouldbeaddressedtoAmberVyas;[email protected];[email protected]
Received31August2013;Accepted25December2013;Published9February2014
AcademicEditors:H.FujitaandC.Schepis
Copyright©2014AmberVyasetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,
whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.
Approximately95%ofthepopulationsuffersatsomepointintheirlifetimefromacnevulgaris.Acneisamultifactorialdiseaseof
thepilosebaceousunit.Thisinflammatoryskindisorderismostcommoninadolescentsbutalsoaffectsneonates,prepubescent
children,andadults.Topicalconventionalsystemsareassociatedwithvarioussideeffects.Noveldrugdeliverysystemshavebeen
usedtoreducethesideeffectofdrugscommonlyusedinthetopicaltreatmentofacne.Topicaltreatmentofacnewithactive
pharmaceuticalingredients(API)makesdirectcontactwiththetargetsitebeforeenteringthesystemiccirculationwhichreduces
the systemic side effect of the parenteral or oral administration of drug. The objective of the present review is to discuss the
conventionaldeliverysystemsavailableforacne,theirdrawbacks,andlimitations.Theadvantages,disadvantages,andoutcome
ofusingvariouscarrier-baseddeliverysystemslikeliposomes,niosomes,solidlipidnanoparticles,andsoforth,areexplained.This
paperemphasizesapproachestoovercomethedrawbacksandlimitationsassociatedwiththeconventionalsystemandtheadvances
andapplicationthatarepoisedtofurtherenhancetheefficacyoftopicalacneformulations,offeringthepossibilityofsimplified
dosingregimenthatmayimprovetreatmentoutcomesusingnoveldeliverysystem.
1.Introduction hyper proliferation of Propionibacterium acne, and inflam-
matoryresponseinitiatedbybacterialantigensandcytokines
Approximately95%ofthepopulationsuffersatsomepointin
[8–14]. Figure1 highlights the difference between a normal
theirlifetimefromacnevulgaris[1].Papules,pustules,closed
skin and the skin with acne. In the skin with acne due to
andopencomedones,cysts,andscarringmaybeseen.Having
the excess production of male hormone androgen and oil
acnecangiverisetofeelingsofembarrassment,lossofself-
producing glands in the face comedone occurs on the face
esteem,anddepression,aswellasphysicalsymptoms(suchas
[15].Theclosedcomedone(whitehead)andripencomedone
soreness and pain) associated with individual lesions. Acne
(blackhead)aretheprimarytwononinflammatorylesionsin
is well known to respond to hormones, both endogenous
acne. These lesions may progress to inflammatory papules
andexogenous.Itisthemostcommondermatologicdisorder
andpustuleswhenthecontentsrupture.Larger,morepainful
affecting approximately 85% of the teenagers [2, 3] and a
lesions,suchascystsandnodules,mayalsodevelop[16].The
chronicinflammatoryfolliculardisorderoftheskin,occur-
application of novel delivery systems to the skin distributes
ringinspecializedpilosebaceousunitsonthefaceconsisting
the topical agent gradually, reduces the irritancy of some
ofthefollicularcanalwithitsrudimentaryhair,andthegroup
antiacnedrugs,andshowsgoodefficacy[17].
ofsebaceousglandsthatsurroundandopenontothefollicle
[4–6].
Acne vulgariscan be defined asthemost commonskin 2.StatusofAcne
disease, that results in comedos or severe inflammatory
lesions in the face, back, and chest with a large number The severity of acne is rated according to the combined
of sebaceous follicles, and the condition of the disease is acne severity classification that classifies acne into mild,
associatedwiththeelevatedrateofsebumexcretion[7].The moderate, and severe based on the number and type of
pathophysiologyofacneincludesabnormalproliferationand lesions. Tables1and2 enlist the features of different types
differentiationofkeratinocytes,increasedsebumproduction, of acne classified according to their general features and
2 TheScientificWorldJournal
Healthy pore of skin with no infection Skin with acne
A blocked pore, a
Hair and sebum come
Hair blackhead
through pore
Infected with
P.acnesbacteria
New skin cells
made here Sweat gland Hair often breaks
Sebaceous gland to be
Blocked sebum
made sebum (oil)
Figure1:Differencebetweennormalskinandskinwithacne.
Table1:Typesofacne. Global acne market forecast,2001−2016
4
Sr.no Typeofacne Features
CAGR (2009−2016)=0.7%
Whitehead(closed):adilatedhair 3 CAGR (2001−2009)=0.8%
folliclefilledwithkeratin,sebum, n)
b
aonpdenbiancgtetoriath,wesitkhina.nobstructed ues ($ 2
Comedonal n
1 Blackhead(open):adilatedhair e
(noninflammatory) ev
folliclefilledwithkeratin,sebum, R 1
andbacteria,withawideopeningto
theskincappedwithablackened
0
massofskindebris.
2001 2009 2016
Papule:smallbumplessthan5mm
Papulopustular indiameter. Figure2:Futureforecastofacne.
2
(inflammatory) Pustule:smallerbumpwithavisible
centralcoreofpurulentmaterial.
Nodular Nodule:bumpgreaterthan5mmin of the market with generics and the increased acceptance
3
(inflammatory) diameter. of alternative therapies such as photodynamic therapy and
ultraviolet (UV)/blue light therapy. The current market has
several products, which act on acne by targeting different
Table2:Typesofacneaccordingtoseverity.
etiologic factors involved in the development of acne [19].
Prevalence of acne declines dramatically after the age of
Sr.no Typeofacne Features
25 to 8%. Acne affects between 40 million and 50 million
Fewerthan20comedonesorfewerthan
individuals in the United States [20]. In India the antiacne
1 Mildacne 15inflammatorylesions,ortotallesion
marketwas130crores,andgrowingattherateof14%annually
countfewerthan30
according to the report of 2009, it would perhaps be now
20–100comedones,or15–50
estimatedasperthegrowthstandardstosomewherearound
2 Moderateacne inflammatorylesions,ortotallesion
Rs.168.94orRs.169croresincomingyears.
count30–125
Morethan5nodules,orTotal
3 Severeacne inflammatorycountgreaterthan50,or 3.TreatmentStrategiesUsedforAcne
Totallesioncountgreaterthan125
Accordingly, no simple recipe for treatment can be given,
and treatment options vary with the stage and intensity of
thedisease[21–24].Accordingtotheevolution,acnecanbe
severity [18]. The acne therapeutics market is forecast to
classified as mild, moderate, or severe. Topical treatment is
show moderate growth in revenues till 2016. The research
thefirstchoiceinmildandmoderateacne,whereassystemic
suggests that the global acne market was worth $2.8 billion
therapyisusedtotreatsevereandmoderatecases[25].Acne
in2009.Itisestimatedtoreachrevenuesof$3.02billionby
ismainlytreatedinthreedifferentways.
2016 at a compound annual growth rate (CAGR) of 0.7%.
Figure2 highlights the global market forecast of acne. The (a)Topical therapy: it includes the use of antibiotics,
moderateincreaseinrevenuesisattributedtoovercrowding retinoids,andcombinationmedication.Topicalacne
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Table3:Systemicandhormonaltreatmentforacne.
(a) Systemictreatment
Antibiotic Name Dose Duration Drawbacks
Oralantibiotics
Gastrointestinalupset,vaginalcandidiasis,
Tetracycline,Oxytetracycline 250–500mgtwicedaily 4–6months
decreasedcompliance
Doxycycline 50–100mgtwicedaily 4–6months Gastrointestinalupset,photosensitivity
Tetracyclines Vertigo,hyperpigmentationofskinandoral
Minocycline 50–100mgtwicedaily 4–6months
mucosa,expensive
Lymecycline 150–300mgdaily 4–6months
Gastrointestinalupset,vaginalcandidiasis,
Erythromycin 500mgtwicedaily 4–6months
Macrolides emergenceofresistanceofP.acnes
Azithromycin 250mgthreetimesaweek 4–6months Gastrointestinalupset
(b) Hormonaltreatment
Name Dose Duration Drawbacks
Spironolactone 25–100mgtwicedaily 6months Menstrualirregularities,contraindicatedinpregnancy
Prednisone 2.5–5mgdaily Indefinitely Adrenalsuppression
Dexamethasone 0.125–0.5mgdaily Indefinitely Adrenalsuppression
Cyproteroneacetate/ethinyl 2mg/35–50𝜇g 6months Vascularthrombosis,melasma,weightgain
estradiol(oralcontraceptives)
Levonorgestrel/ethinylestradiol 100𝜇g/20𝜇g 6months Vascularthrombosis,melasma,weightgain
medications are usually irritating to the skin; more the development of oral isotretinoin (sold as Accutane and
than 40% of acne bacteria are insensitive to oral Roaccutane)in1980[27].Also,someantibioticslikeminocy-
antibioticsandareassociatedwithpossiblesevereside clinewereusedfortreatmentforacne[28,29].
effectsandhighcost. From the nineteenth to twentieth century, almost all
(b)Systemic treatment includes oral antibiotics, reti- the treatments of acne were based on conventional system.
noids, and hormonal treatment. Systemic treatment Conventionalavailable dosage forms/delivery system works
is indicated for the management of moderate and by the following four mechanisms, namely, normalizing
severeacne,acnethatisresistanttotopicaltreatment shedding into the pore to prevent blockage, killing propi-
andacnethatcoverslargepartsofthebodysurface. onibacteriumacnes,anti-inflammatoryeffects,andhormonal
Table3 highlights the drugs used in systemic and manipulation[8,14].Inspiteofvariousavailabletreatments
hormonaltreatmentofacne. foracne,manypatientsfailtorespondadequatelyordevelop
problematic side effects. Most of the conventional available
(c)Other treatments include those which are not in
formulationsusuallyproduceahighincidenceofsideeffects
abovetwocategorieslikeresurfacing,dermabrasion,
and symptoms that diminish the patient compliance, com-
chemicalpeels,xenografts,heterograft,autograftand
promisingtheefficacyofthetherapy[30–32].Nevertheless,
fat transplantation. Figure3 enlists a detailed over-
some of them also lead to skin dryness, peeling and skin
view of all the strategies used in treatment of acne
irritation,orbacterialresistance[33–37].Table4explainsthe
alongwiththeirexamples.
side effects associated with the conventional formulations
usedinacne.
4.ConventionalDeliverySystemUsedin
To reduce these above mentioned side effects, develop-
TreatmentofAcne
mentofnovelcarrier-baseddrugdeliverysystemscameinto
existence. The application of these novel delivery systems
In earlier days, people all over the world used conven-
is advantageous to the skin as it distributes the topical
tionalsystemfortreatmentofacne.Inthe1950s,antibiotics
agent gradually and in some cases has demonstrated the
proved to be effective in treating acne because of the anti-
inflammatory effects of tetracycline. Retin A, discovered in abilitytoreducetheirritancyofsomeantiacnedrugs,yetit
the 1960s, was found to fight acne blemishes. Accutane, a maintainsabetterefficacywhencomparedwithconventional
form of vitamin A for reducing oil made by skin glands, formulations[17].Thenoveldrugdeliverysystemsalsohave
wasintroducedasatreatmentinthe1980s.Lasertreatments the advantage of penetrating more efficiently into the hair
for treating acne began in the 1990s and were found to be folliclesthandononparticulatesystems,suchasconventional
especially effective for people suffering from nodular and formulations,solongasthesizeisselectedinanappropriate
cysticacne.Inthe1970s,tretinoin(originalTradeNameRetin manner. This provides a high local concentration over a
A) was found to be effective for acne [26]. This preceded prolongedperiod[38–40].
4 TheScientificWorldJournal
Table4:Topicalconventionaldeliverysystemusedforacne.
Conventionaldeliverysystem Drug Sideeffects Reference
Benzoylperoxide Peeling,itching,redness,dryness,burning,anddermatitis [41]
Clindamycin Peeling,itching,redness,dryness [42]
Tretinoin Erythema,scaling,burning [43]
Lotion
Erythromycin Erythema,scaling,burning [44]
Glycolicacid Itching,rash,pruritus [45]
Tretinoin Itching,rash,pruritus [45]
Adapalene Erythema,scaling,dryness,burning,stinging,irritation,sunburn [46]
Tazarotene Erythema,scaling,burning [47]
Cream Azelaicacid Itching,rash,pruritus [45]
Teaoil Burning,itching,irritation,stinging [48]
Clindamycin Erythema,desquamation [49]
Salicylicacid Erythema,dryness,dermatitis [41,50]
Erythromycin Dryness,erythema,peeling,dermatitis [44,51]
Gel Benzoylperoxide Dryness,erythema,peeling,dermatitis [51]
Adapalene Erythema,scaling,dryness,burning,stinging,irritation [46]
Dapsone Peeling,itching,redness,burning [52]
Emollient Sodiumsulfacetamide-sulfur Dryness,irritation,redness,scaling,stinging,orburning [53]
Strategies used for treatment of acne
Resurfacing
Dermabrasion
Laser
resurfacing
Chemical peels
Systemic Xenograft
Topical treatment Other Fat
treatments transplantation
treatment
Antibiotics Combination medications Oral retinoid
Adapalene-benzoyl peroxide
Azelaic acid Isotretinoin
Benzoyl peroxide Retinoids Benzoyl peroxide-clindamycin Oral antibiotics
Clindamycin Tretinoin-clindamycin
Tazarotene
Dapsone Tetracycline
Erythromycin Tretinoin Doxycycline
Adapalene
Minocycline Hormonal treatment
Erythromycin
Azithromycin Spironolactone
Prednisone
Dexamethasone
Figure3:Treatmentstrategiesusedforacne.
5.NovelDrugDeliverySystemUsedto (liposomes,polymericmicrospheres,andsolidlipidnanopar-
TreatAcne ticles) for topical treatment are advantageous compared to
conventionalavailabletopicaldeliverysystem.Theencapsu-
Theefficacyoftheantiacnetopicaldrugsusingnovelcarrier- lationofantiacnedrugsinvesicularandparticulatedelivery
baseddrugdeliverysystemiswellestablished.Thelocalside systemsrepresentsaninnovativeandalternativeapproachfor
effects,however,mainlycutaneousirritation,erythema,dry- minimizingthesideeffectsandpreservingtheirefficacy.
ness,peeling,andscaling,remainmajorproblems.Theanti- Noveldrugcarriersintendedforuseinskindiseasesare
acnedrug-loadedvesicularandparticulatedeliverysystems oftendesignedtoincreasetheloadabilityofAPIsandreduce
TheScientificWorldJournal 5
Novel carrier-based drug delivery system
Liposome Niosome Liposphere Microsponge
Hydrophilic
phase
Lipid
(solid) Hydrophobic
phase
Cosurfactant
Surfactant
Solid lipid Nanostructured Microemulsion Fullerene
nanoparticles lipid carriers
Figure4:Novelcarrier-baseddrugdeliverysystemfortreatmentofacne.
sideeffect.Indermatotherapy,researchonnewdrugentities 5.1.1. Advantage of Liposomal Formulation. After topical
and drug delivery systems is focused on frequent diseases application, liposome can improve drug deposition within
often difficult to treat, in particular acne and psoriasis theskinatthesiteofaction,reducessystemicabsorption,and
[54].Forseveremanifestations,notinfrequenthighlyactive minimizesthesideeffectstherebyprovidinglocalizedeffect
APIs, which may also induce major unwanted effects, have [59].Theycantargetthedrugtoskinappendagesinaddition
to be prescribed for systemic use. Progress in novel drug andincreasethesystemicabsorption[60].Theycanimprove
delivery systems may allow the safer use of these agents by the therapeutic effect of drugs and decrease the adverse
the topical route [55]. The novel carrier systems that are effects. It has been reported that formulations of vesicular
under investigation for application and treatment of acne systemleadtobetterresultinthetreatmentofacnecompared
include liposome, niosome, microsponge, microemulsion, toconventionalsystembyreleasingthedrugontargetsinskin
microsphere,SLN,hydrogel,aerosol,fullerenesandsoforth appendagesandthesesystemsaremoresuitableforlipophilic
[54, 55]. Controlled drug release of these novel carrier- drug[14,17].Table5enliststheexamplesofvariousliposomal
based delivery systems and subsequent biodegradation are formulationsusedinacne.
essential for developing successful formulations. The drug
release mechanism of these systems involves desorption of
5.1.2.DisadvantageofLiposomalFormulation. Themajordis-
adsorbeddrug,diffusionthroughthecarriermatrix,erosion,
advantageofliposomalformulationisrelatedtoitsstability
and combination of erosion and diffusion method. Along
aspect.Thestabilityissueofliposomesremainsanarea,which
withthenumerousadvantages,novelvesicularcarriersystem
issurroundedbyanumberofproblems;duetotheformation
isassociatedwithsomeseriousdisadvantageswhichrestrict
of ice crystals in liposomes, the subsequent instability of
their use: drugs passively may lead to low drug loading
bilayers leads to the leakage of entrapped material. The
efficiencyanddrugleakageinpreparation,preservation,and
physicalinstabilityisalsofacedbyliposomes.Theoxidation
transport in-vivo. Also, the major problem of their stability
of cholesterol and phospholipids leads to the formulation
acts as a barrier and limits their use [56]. The novel carrier
instability. Chemical instability indicates the hydrolysis and
based delivery systems are discussed with their advantages,
oxidationoflipids.Thedestabilizationofliposomesisdueto
limitations, and suitable examples. Figure4 shows various
thelipidexchangebetweentheliposomesandHDLs[61].
carrier-based drug delivery systems used in treatment of
acne.
5.2. Niosomes. Niosomes are unilamellar or multilamellar
5.1.Liposomes. Liposomesaresphericalparticlescomposed vesicleswhereinanaqueousphaseisencapsulatedinhighly
ofone,several,ormultipleconcentricmembranes[57].They orderedbilayermadeupofnonionicsurfactant[62].Theyare
are potent drug delivery systems for treating hair follicle- nonionic surfactant vesicles by which skin penetration and
associateddisorderssuchasacne[58]. accumulationareincreasedinthesuperficialskinstrata[63].
6 TheScientificWorldJournal
Table5:Novelcarrier-baseddeliverysystemforacne.
Drug Objective Outcomes Reference
Liposomalformulation
Asignificantantibacterialeffectinthe
Toimprovetheantibacterialefficacyof infundibulaagainstbothP. acneand
Benzoylperoxide [64]
benzoylperoxide Micrococcaceaewasobservedascomparedtothe
conventionalformulation.
Clindamycin Toimprovethestabilityandpenetrability Increasedstabilityandintradermalpenetrability [65]
Liposomalformulationproducedfivefoldhigher
depositionofdruginskinthanthecorresponding
Salicylicacid Toreduceassociatedsideeffects [66]
plaindrugsolutionandconventionalgeland
reducedskinirritationwasobserved.
Toimprovethestabilityandthe Increasedstabilityanddrugretentionwere
Tretinoin [67]
thermodynamicactivity achieved.
Toincreaseskintargetingandskin Increaseskintargeting,drugdepositionand
Isotretinoin [68]
depositionandreduceskinirritation. decreaseskinirritationwereobserved.
Lauricacidloadedliposomesreleasethedrug
Lauricacid Toevaluatetheantimicrobialactivity directlyintothebacterialmembranes,thereby [14]
killingthebacteriaeffectively.
Cyproteroneacetate Toincreasepercutaneousabsorption Betterpenetrationwasobserved [69]
Toincreaseskinpermeation,deposition, Higherdepositionofdruginskin,increased
Finasteride [70]
andstabilityofthedrug. permeationandstabilitywereobserved.
Teaoilliposomedisruptedthepermeability
Teaoil Toincreaseskinpermeabilityofdrug. barrierofcellmembranestructuresandincreased [48]
thepermeability.
Liposomalformulationdeliveredthemethylene
Toevaluatetheefficacyandtolerabilityof
Methyleneblue bluetosebaceousglandandwaseffectivein [71]
liposomesloadedmethyleneblue.
treatmentofmild-to-moderateacnevulgaris.
Niosomeformulation
Niosomalgelimprovedtheskinretention,
Benzoylperoxide Toreducetheassociatedsideeffects therapeuticresponseandconsiderablyreduced [72]
theadversesymptoms.
Niosomalformulationimprovedthecutaneousor
Toimproveskindrugretentionofdrugand
Tretinoin transdermaldeliveryofalipophilictretinoinand [63]
increasephotostability.
increasedphotostability.
Niosomalgelwassignificantlymorestableas
Toenhancedrugretentionintoskinand
Erythromycin comparedtoplaindruggelandmarketedgeland [72]
improvestability.
drugretentionwasincreased.
Microspongeformulation
Benzoylperoxide Toreduceskinirritation. Controlledreleaseandreducedskinirritation [73]
Controlledreleaseoftretinoinwithreduced
Tretinoin Toreducecutaneoussideeffect [74]
cutaneoussideeffects.
Microemulsionformulation
Novelmicroemulsionincreasestretinoin
Toincreaseskinpermeationandskin penetrationthroughskinandmaximumamount
Tretinoin [75,76]
retention. ofdrugretainedascomparetoplaindrugin
solution,gelandmarketedpreparation.
TheO/Wmicroemulsionscontainingacounter
Toincreaselipophilicityandskin
Retinoicacid ionincreasedtheskinpermeabilityand [77]
permeability.
lipophilicityofdrug.
Microsphereformulation
Creamcontainingmicrospheresofbenzoyl
Toreduceskinirritationontopical
Benzoylperoxide peroxideofferedfavorableefficacywithaverylow [78]
treatment.
potentialforirritation.
Toreducecutaneousirritation,including
Microsphereformulationreducedlocalside
Tretinoin erythema,peeling,dryness,burning,and [79]
effectsandsustainedreleasewasachieved.
itching.
Controlledreleaseofdrugwasproducedby
Alltransretinoicacid Tocontrolthereleaseofdrug. [80]
encapsulationofdrugintothemicrosphere.
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Table5:Continued.
Drug Objective Outcomes Reference
Solidlipidnanoparticlesformulation
Lesserskinirritancy,greaterskintolerance,
Toevaluatethepotentialofalipophilicdrug occlusivity,slowdrugrelease,andincreased
Tretinoin withrespecttoprimaryskinirritation,in permeabilitywereobservedwiththedeveloped [81]
vitroocclusivityandskinpermeation. tretinoinloadedSLN-basedgelsmorethanthe
commercialproduct.
SLNloadedwithisotretinoinsignificantly
Isotretinoin Toevaluateskinpenetration increasedtheaccumulativeuptakeofdruginto [82]
theskinandenhancedtheskinpermeation.
Toproducecomedolyticeffectandreduce SLNproducedcomedolyticeffectsandepidermal
Alltransretinoicacid [73]
skinirritation. thickeningwithreducedskinirritation.
SphingosomeSLNenhancedthepermeationof
Sphingosome Toincreaseskinpermeationofdrug. [83]
thedrugthroughtheskintoacnelesion.
CPAattachedtoSLNincreasedskinpenetration
atleastfour-foldovertheuptakefromcreamand
Cyproteroneacetate Toreducesideeffectandimproveskin
nanoemulsion.Incorporationofdrugintothe [84]
(CPA) penetrationandabsorption.
lipidmatrixofNLCresultedina2to3fold
increaseinCPAabsorption.
Triclosannanoparticleincreasedthestabilityand
Toincreasestability,skinretentionand
Triclosan showedhigherretentionandpermeabilitythan [85]
permeability.
conventionalcreamformulation.
Hydrogelformulation
Triclosanpermeabilitywasincreasedbyusing
Triclosan Toincreasethepermeabilitythroughskin. [86]
transcutolasapermeationenhancer.
Thecomplexationoftretinoinwith
dimethyl-𝛽-cyclodextrinovercomethedrug’slow
Toincreasereleasepermeationandreduce watersolubilitytherebyincreasingdrugrelease
Tretinoin [87]
skinirritationoftretinoin. andenhancedthedrugpermeationbypromoting
skinabsorptionandalleviatedruginducinglocal
irritation.
Aerosolfoamsformulation
Juniperoilsolidlipidmicroparticlessubstantially
Toreducethevolatilityandmaintain maintaintheoilloadedinsidetheirlipidic
Juniperoil [88]
antibacterialactivity. structure,reducingitsvolatilityandretainingits
antibacterialactivity.
5.2.1. Advantage of Niosomal Formulation. Niosomes are 5.2.2. Disadvantages of Niosomes. Although niosomes are
one of the promising drug delivery systems in the treat- superior to liposomes, they have some stability problems
ment of skin disorders. When applied topically, niosomes associated with them such as physical stability of fusion,
can enhance the residence time of drug in the stratum aggregation, sedimentation, and leakage on storage. The
corneum and epidermis, while systemic absorption of the major issue is the hydrolysis of encapsulated drugs which
drug can be reduced [89–92]. They also increase the horny limitstheshelflifeofthedispersioninniosomes[96].
layer properties by reducing transepidermal water loss and
increasing the smoothness via replenishing lost skin lipids 5.3.Microsponges. Microspongesareuniform,spherical,and
[63, 93, 94]. Table5 describes the niosome formulations porous polymeric delivery system having size range of 5–
and their outcomes for treatment of acne. Both niosomes 300𝜇m[97,98].Theyrepresentamyriadofinterconnecting
andliposomesareequiactiveindrugdeliverypotentialand voids within a noncollapsible structure with a large porous
both increases the drug efficacy as compared with that of surfaceloadedwiththeactiveagent[54].Itisamicroscopic
free-drug. Niosomes are preferred over liposomes because spherecapableofabsorbingskinsecretions,thereforereduc-
the former exhibit high chemical stability and economy. ingtheoilinessoftheskin.
One of the reasons for preparing niosomes is that they
assume higher chemical stability of the surfactants than 5.3.1. Advantage ofMicrosponge. Topicalagentsareamain-
that of phospholipids, which are used in the preparation of stay in cosmetics and the treatment of dermatological
liposomes.Duetothepresenceofesterbond,phospholipids disorders. Microsponge delivery system when applied to
areeasilyhydrolysed[95]. the skin, the release of drug can be controlled through
8 TheScientificWorldJournal
diffusion or other variety of triggers, including rubbing, 5.5.1.AdvantageofMicrospheres. Microsphereswhenadmin-
moisture, pH, friction, or ambient skin temperature [99]. isteredtotheskin,theamountoffreedrugintheformulation
Controlled release of drug from a delivery system to the penetrates into the epidermis and is compensated by drug
skincouldreducethesideeffectwhilereducingpercutaneous release from the microspheres. This system offers sustained
absorption. Microsponges are capable of absorbing skin drugdeliverywithoutoverloadingtheepidermisorresulting
secretions, therefore reducing oiliness and shine from the anincreaseinthetransdermalpenetration[40,42].Table5
skin. Microsponge polymers possess the ability to load a enliststhemicrosphereformulationsofdrugsusedintreat-
wide range of actives providing the benefits of enhanced ment of acne. Microsphere formulation of topical tretinoin
product efficacy, mildness, tolerability, and extended wear and BPO (benzoyl peroxide) currently on the market has
to a wide range of skin therapies [100, 101]. As compared demonstratedgoodefficacyandtolerabilityandisexpected
to liposomes, which suffer from lower payload, difficulty to encourage adherence and long-term therapeutic benefit.
in formulation, limited chemical stability, and microbial Microsphereencapsulationprotectsthestabilityofdrugsand
instability,themicrospongesystemincontrastisstableover makesthemphotostable.Furthermore,microspheresappear
∘
rangeofpH1to11andtemperatureupto130 C;compatible to absorb sebum from the skin’s surface, reducing oiliness,
withmostvehiclesandingredients,self-sterilizingasaverage whichisacommoncomplaintamongacnepatients[107].
poresizeis0.25𝜇mwherebacteriacannotpenetrate,higher
payload (50 to 60%), still free flowing, and cost effective 5.6.SolidLipidNanoparticles(SLNs). Solidlipidnanoparti-
[9,10].Oneofthemostsuitableexamplesisthemicrosponge cles(SLN)wereintroducedintheyear1991andtheyembody
of benzoyl peroxide, for topical delivery which maintained an alternative carrier system to tradition colloidal carriers
efficacywithdecreasedskinirritationandsensitization[102]. suchasemulsions,liposomes,andpolymericcarriers.Solid
Table5showsthevariousmicrospongedeliverysystemsused lipid nanoparticles (SLNs) are particles made from solid
fortreatmentofacne. lipids with a mean diameter between approximately50 and
1000nm,whicharenormallystabilizedbylecithin[108,109].
5.4.MicroemulsionandNanoemulsion. Microemulsionsare The reasons for the ever-increasing applications of lipid
transparentdispersions of oiland water having droplet size basedsystemaremanyfoldandincludethefollowing:lipids
of 100nm in diameter stabilized by an interfacial film of enhance the oral bioavailability and reduce plasma profile
surfactantandcosurfactantmolecules[103,104].Surfactant variability, better characterization of lipoid excipients, and
andcosurfactantareusedtodecreasetheinterfacialtension an improved ability to address the key issues of technology
betweenoilandwaterphase[47]. transferandmanufacturescale-up.
5.4.1. Advantage of Microemulsion. (Co-)surfactant acts as 5.6.1. Advantage of SLN. The release rate of the drug from
penetrationandocclusivityenhancerthatimprovesskinpen- SLNsdependsonthepresenceofthedruginthesolidlipid
etration to variable degrees [105]. In microemulsion, active matrix.Ifthedrugislocalizedonlyintheoutershell,burst
agents are solubilised and thus they are available for quick release will be obtained and not controlled release. If the
penetration into the skin. Nanoemulsions (oil in water or drug is homogeneously distributed within the lipid matrix,
waterinoilformulation)arecharacterizedbythedispersion however,controlledreleasecanbeachieved[110,111].Table5
ofverysmallsizeddropletswhenmixed.Theyareappropriate enliststheSLN-basedformulationsforacne.
carrier for the transport of lipophilic compounds into the
5.6.2.DisadvantagesofSLN. Someoftheparameters,which
skin and are considered as ideal vehicle for use in acne.
hinder the use of SLN, are particle growth, unpredictable
This increases the penetration of active component inside
gelation tendency, and unexpected dynamics of polymeric
the lipophilic environment of the pilosebaceous unit. They
transitions.
alsoproduceadditionaltherapeuticeffectslikeincreasedskin
hydration and viscoelasticity. Table5 highlights the various
5.7.Hydrogel. Hydrogelsarethenetworkofpolymerchains
microemulsionformulationsusedinacne.
that are water-insoluble, and sometimes they are found as
a colloidal gel in which water is the dispersion medium.
5.5. Microspheres. Itiswellsaid“pooradherenceisdirectly
Hydrogelsaresuperabsorbentnaturalorsyntheticpolymers
linkedtopoortreatmentresultsandpatientdissatisfaction”
[86,112].
[106]. Irritation commonly associated with topical thera-
pies is one of the most significant factors contributing to 5.7.1. Advantage of Hydrogel. Hydrogels are three dimen-
lack of adherence and therefore therapeutic withdrawal. sional,hydrophilicnetworksthatholdlargeamountofwater
Microspheres are small spherical shaped particles made of or biological fluids, similar to biological tissues. Because
biodegradablepolymerandisfilledwithdrugsubstancethat of this unique property, hydrogels show good biomedical
is dispersed homogenously throughout the core and these applications. By tuning, the physicochemical properties of
spheres when degraded, releases the drug for desired time. the hydrogels suitable modulated drug delivery system are
These microspheres act as a reservoir system for the active generated [112]. Table5 explains the objective of hydrogel
agent[40,54].Microencapsulationtechniqueismainlyused formulationoftriclosanandtretinoin.
for the preparation of the microspheres which provide fine
coating of inert, natural, and synthetic polymeric materials 5.8.AerosolFoams. Theproductspackedunderpressureand
depositedaroundsolidandliquidmicronizedparticles[42]. thatcontaintherapeuticactiveingredients,whicharereleased
TheScientificWorldJournal 9
upon activation of an appropriate valve system, are called example,anantiacneformulationthatcombinesclindamycin
aerosols. These foams are suitable for topical application to (1%)andbenzoylperoxide(5%)utilizesthisnovelpolymer-
theskinandlocalapplicationintothenose,lungs,andmouth. basedgeltechnologyandprovidesexcellenttolerabilityand
Aerosol foams are one of the novel drug delivery system efficacy.
used in treatment of acne vulgaris. Foams are preferred for Despite the availability of numerous effective medical
applicationonlargehairysurfaceslikethechest,back,andin therapiesforacnevulgaris,issuesofsafety,compliance,and
thefaceascleansersduetoeasinessofapplication[113,114]. less than ideal efficacy help drive the search for alternative
treatments for this exceedingly common clinical problem.
5.8.1. Advantage of Aerosol Foams. The physicochemical Recently, scientists have developed effective vaccine for P.
characteristicsofvehiclebaseoftheaerosolfoamarethesame acnes-associatedinflammatoryacne,consistingofacellwall-
asthoseoftheconventionalvehicleslikecreams,lotions,and anchoredsialidaseofP.acnesorkilled-wholeorganismofP.
gels, having a liquid or semisolid consistency, but aerosol acnes[123,124].Theyalsohopetodevelopafuturebacterial
foammaintainsdesirablepropertiessuchasmoisturizingfast therapy for overcoming problems seen with the continuous
dryingeffectsorhigherdrugbioavailability.Gaspressurized useofantibioticssuchasabuildingupabacteriaresistance.
systemisusedtodispensedtheaerosolfoam[113,114].Table5 These scientists of the 21st century are convinced that acne
explainstheobjectiveofaerosolformulationofsalicylicacid isnotduetodirtandthatscrubbingskincanleadtoworse
andbenzoylperoxide. problems.Therefore,inthefuture,itispossibletoexplorethe
useofmicro-andnanocarrier-baseddrugdeliverysystemsin
5.9.Fullerenes. Likehollowsphere,fullerenesaremolecules
advancedformwithincreaseineffectivenessfortreatmentof
composed of carbon. It is reported that when fullerenes
acne.
are exposed to the skin, they migrate through the skin
intercellularly,asopposedtomovingthroughcells.Therefore, 5.12. Nanostructured Lipid Carriers. Nanostructured lipid
a fullerene could be used to “trap” active compounds and carriersaresmartersecond-generationdrugcarriersystems
then release them into the epidermis once they are applied having solid matrix at room temperature. This carrier sys-
ontheskin.Moreover,fullerenes,themselves,arethoughtto tem is usually made up of physiological, biodegradable,
be potentially potent antioxidants. Literature on fullerenes and biocompatible lipid materials and surfactants and is
proved that they can be tolerated and can hold substantial acceptedbyregulatoryauthoritiesforapplicationindifferent
promiseindermatologicandcosmeticapplications. drug delivery systems. NLCs exhibit superior advantages
over other colloidal carriers like nanoemulsions, polymeric
5.9.1. Advantage of Fullerenes. Fullerenes are an excellent
nanoparticles,liposomes,SLN,andsoforthandthustheyare
antioxidant and a safe material for the suppression of acne
beenexploredtomoreextentindrugdelivery.
vulgaris.Thisoccurredbytheinhibitionoflipidperoxidation
because of fullerene’s antioxidant activity and the suppres-
5.12.1.AdvantagesofNLCs. Theuniquesetofadvantagesof
sion of sebum production without the production of any
NLCs includes enhanced drug loading capacity, prevention
side effects. Thus, fullerenes can serve as novel carriers for
of drug expulsion, and more flexibility for modulation of
treatmentofacne.
drug release. For example, Zhou, prepared adapalene (a
retinoidantiacnedrug)loadednanostructuredlipidcarriers
5.10. Lipospheres. Lipospheres are lipid-based encapsula-
fortopicaluse.TheseNLCswereabletoaccumulateinhair
tion system, used for topical drug delivery of various
follicles and improve the follicular delivery of adapalene.
medicaments.Lipospheresconsistsofwaterdispersiblesolid
Thus,NLCscouldbepromisingcarriersfortopicaldelivery
microparticles, which have diameter ranging from 0.1 to
ofantiacnedrugs.
100𝜇m.Inliposphere,solidhydrophobicfatcoreisstabilized
byalayerofphospholipidmoleculesembeddedintheirsur-
5.13. Cyclodextrin Based Carriers. Cyclodextrins (CDs) are
faces,whichareapotentialgroupofpenetrationenhancers
afamilyofcyclicoligosaccharidesderivedfromstarchcon-
[115–119].
taining six (𝛼-CD), seven (𝛽-CD), eight (𝛾-CD), or more
5.10.1. Advantage of Lipospheres. Better physical stability, (𝛼-1,4)-linked𝛼-D-glucopyranoseunits.Theytaketheshape
highdispersabilityinaqueousmediumandprolongedrelease of a truncated cone or torus instead of a perfect cylinder
ofvarioustypesofdrugsincludinganti-inflammatorycom- becauseofthechairconformationoftheglucopyranoseunits.
pounds,localanesthetics,antibiotics,andanticanceragents These versatile, pharmaceutical-material CDs are classified
arepossibleusingthistypeofsystem[120–122]. into hydrophilic, hydrophobic, and ionic derivatives [125].
Cyclodextrin complexation is a well known technique for
5.11. Polymers. Polymers are large molecules, which consist enhancingthesolubilityandstabilityofdrug,sustainingthe
of repeating structural units of monomers connected by release and minimizing the photo degradation of drug. In
chemical covalent bonds. In dermatology, the new acrylic particular,thefocusofinvestigationinvolvesthecombination
acid polymer turns into gel in presence of water by trap- ofvesicularapproachwithcyclodextrincomplexation(dual
ping water into microcells. A stable gel-like formulation approach)whichwouldhelpinincreasingthesolubility,skin
containinghydrophiliccompoundassolutionandlipophilic permeation, and deposition and reducing the photodegra-
compound in the form of suspension is easy to use, and it dation of drugs. Nowadays drug-cyclodextrin-vesicles dual
releases the active compound after single application. For carrier approach for targeting of antiacne agent to skin is
10 TheScientificWorldJournal
used.Forexample,Kauretal.preparedisotretinoin-hydrox- Acknowledgments
ypropyl-𝛽-cyclodextrin (HP-𝛽-CD) inclusion complex and
TheauthorsarethankfultoDirector,UniversityInstituteof
encapsulated this complex in elastic liposomes and studied
Pharmacy,PtRavishankarShuklaUniversityRaipur,Chhat-
the effect of dual carrier approach on skin targeting [68].
tisgarhforprovidingnecessaryinfrastructuralfacilities.The
The isotretinoin elastic liposomal formulation possessed
authorsarealsothankfultoChhattisgarhcouncilofscience
great potential for skin targeting, prolonging drug release,
andtechnology,CCOST/MRP/2012Endt.No.1926andUni-
reductionofphotodegradation,reducingskinirritation,and
versity Grant Commission, UGC-MRP F. No. 42-706/2013
improvingtopicaldelivery.
(SR)forprovidingfinancialassistancerelatingtothiswork.
AuthorsalsowanttothanklibraryofPt.RavishankarShukla
6.Conclusion Universityforprovidinge-resourcesavailablethroughUGC-
INFLIBNET.
Adolescent stage is a complex life cycle characterized by
manystrikingbiological,psychological,physical,andsocial
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