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Topical microemulsions containing vitamins C and E: from formulation optimisation to evaluation using reconstructed human epidermis : doktorska disertacija
ID Rozman, Branka (Avtor), ID Gašperlin, Mirjana (Mentor) Več o mentorju... Povezava se odpre v novem oknu

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Izvleček
The novel role of oxidants and antioxidants in skin ageing as well as in various skin disorders and diseases has opened new research areas in several disease states and their therapeutic strategies. Successful prophylaxis and therapy of reactive-oxygen mediated skin ageing and phatogenesis would necessitate control of oxidant/antioxidant balance in the affected site, which can be achieved by external supply of skin endogenous antioxidants. However, antioxidants’ skin biovailability is usually low, mainly due to their poor aqueous solubility, inefficient permeability or instability during the storage. Colloidal drug delivery systems, like microemulsions (ME), nanoparticles or liposomes, are applicable to overcome the stability and pharmacokinetic problems associated with antioxidant delivery. These systems offer better targeting to upper skin layers, with faster onset and lower concentrations of the antioxidants needed. Moreover, liposomes and ME have a unique ability to simultaneously deliver both lipid- and water-soluble antioxidants. The thesis focuses on topical ME simultaneously loaded with lipophilic vitamin E, skin’s major membrane antioxidant and hydrophilic vitamin C, the main component of skin water-soluble antioxidant defence. Initially, viscosity of liquid o/w and w/o ME both composed of the same ingredients has been optimized for topical application. Among thickening agents tested carbomer, colloidal silica and mixture of xanthan and alginate revealed as suitable thickeners for o/w ME and white wax and colloidal silica for w/o ME. Transparent microemulsion gel (gel-like ME) that has been formed upon the addition of specific amounts of water to liquid o/w ME has been investigated as an alternative solution to viscosity problem. Gel-like ME was found to offer the best protection for both vitamins, although other ME also significantly increased their stability compared to solution. In the presence of vitamin C no decrease in vitamin E content occurred. The addition of thickeners to ME changed the stability of at least one vitamin, but the systems still protected vitamins better than solutions, the exception being o/w ME thickened with mixture of xanthan and alginate. By varying the composition of ME, absorption of vitamins C and E in reconstructed human epidermis was significantly modulated. The absorption of vitamins C and E in epidermal and collagen layer was in general enhanced by ME when compared to solutions. The location of the antioxidants in the ME and affinity for the vehicle appeared to be crucial in the case of non-thickened ME. Addition of collidal silica to ME enhanced the deposition of vitamins E and C in the reconstructed human epidermis. The addition of colloidal silica to either o/w or w/o ME also increased skin bioavailability of both vitamins. Dual influence of colloidal silica on skin delivery of vitamins C and E from topical ME was confirmed: it affected formulation characteristics and had a direct impact on the skin. The temperature-driven changes in the microstructure of gel-like ME together with their influence on skin deposition of vitamins C and E were confirmed by rotational rheometry, viscosity measurements, droplet size determination and pig ear permeation studies. The release studies have shown that the vitamins’ release at skin temperature from gel-like ME were comparable to those from o/w ME and were much faster and more complete than from o/w ME conventionally thickened with polymer (o/w ME carbomer). Concerning effectiveness in skin delivery of both vitamins o/w ME was found the most appropriate, followed by gel-like ME and by o/w ME carbomer. Finally, the irritation potential of ME was assessed in comparison to commercially available ME. Two different models were used: reconstructed human epidermis as ECVAM validated model for skin irritation testing and NCTC 2544 human keratinocyte cell cultures. Both models confirmed our ME less irritant than commercial product. In summary, ME have been proved effective and non-irritant vehicles with functionally suitable consistency for simultaneous topical delivery of a hydrophilic vitamin C and a lipophilic vitamin E.

Jezik:Angleški jezik
Vrsta gradiva:Doktorska disertacija
Tipologija:2.08 - Doktorska disertacija
Organizacija:FFA - Fakulteta za farmacijo
Kraj izida:Ljubljana
Založnik:[B. Rozman]
Leto izida:2009
Št. strani:94 f.
PID:20.500.12556/RUL-127054 Povezava se odpre v novem oknu
UDK:543:615
COBISS.SI-ID:2527089 Povezava se odpre v novem oknu
Datum objave v RUL:14.05.2021
Število ogledov:573
Število prenosov:68
Metapodatki:XML RDF-CHPDL DC-XML DC-RDF
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Sekundarni jezik

Jezik:Slovenski jezik
Naslov:Dermalne mikroemulzije z vitaminoma C in E: od optimiranja sestave do vrednotenja na modelu človeških keratinocitov
Izvleček:
Mikroemulzije so bistre, termodinamsko stabilne disperzije vodne in oljne faze, stabilizirane z medfaznim filmom emulgatorja. Kot nosilni sistemi za dermalno dostavo učinkovin izkazujejo številne prednosti, saj lahko vanje zaradi njihove specifične zgradbe vgradimo tako vodotopne kot tudi lipofilne in/ali amfifilne učinkovine z namenom povečanja topnosti, hitrosti in obsega absorpcije učinkovine, doseganja prirejenega sproščanja, zaščite nestabilne učinkovine, zmanjšanja variabilnosti biološke uporabnosti ter zakrivanja neprijetnega vonja. Kljub naštetim prednostim je število registriranih mikroemulzij majhno, in sicer predvsem zaradi velikega deleža emulgatorjev, ki so potencialno toksične snovi. Mikroemulzije so pogosto Newtonske tekočine z nizko viskoznostjo, ki so neprimerne za direkten nanos na kožo. Viskoznost mikroemulzij lahko povečamo z dodajanjem zgoščeval, ki ustrezno spremenijo reološko obnašanje sistema, ne da bi pri tem vplivala na druge lastnosti mikroemulzij, kot so stabilnost, bistrost in spontan nastanek. Druga možnost prirejanja viskoznosti je izdelava mikroemulzijskih gelov z izbiro ustreznih sestavin mikroemulzij in določitvijo koncentracij, kjer spontano tvorijo lamelarne strukture, za katere je značilna povečana viskoznost. Koža, radikali in antioksidanti Pri prekomerni izpostavitvi kože UV-svetlobi pride poleg povečanega nastajanja radikalov istočasno tudi do zaviranja delovanja pomembnejših encimov, ki odstranjujejo radikale. Porušenje ravnotežja med nastajanjem radikalov in antioksidativno obrambo v prid prvih lahko privede do poškodb organizma. Tako stanje imenujemo oksidativni stres, ki je eden glavnih dejavnikov pri fotostaranju, vnetjih in celo rakavih spremembah kože. Telo je razvilo številne obrambne sisteme, ki celice varujejo pred presežnimi radikali. Med najpomembnejše obrambne mehanizme štejemo encimski (npr. superoksid dizmutaza, katalaza, peroksidaza) in neencimski (npr. glutation, vitamin E – α-tokoferol, vitamin C – askorbinska kislina, β-karoten, ubikinon) antioksidativni sistem. Obetaven pristop k zaščiti kože pred škodljivimi vplivi radikalov je krepitev endogenega obrambnega sistema. V terapiji se najpogosteje uporabljajo vitamin C, vitamin E in β-karoten. Vitamin C, ki neposredno reagira z vsemi pomembnimi kisikovimi radikali, je glavni in edini življenjsko potreben vodotopen antioksidant, medtem ko je vitamin E najpomembnejši lipofilni antioksidant, ki zagotavlja zaščito pred oksidativno poškodbo membran in je dokazano učinkovit pri preprečevanju lipidne peroksidacije in tvorbe tumorjev kože. Čeprav sta vitamina C in E prisotna v različnih predelih celice, vse več dejstev dokazuje, da je njuno delovanje sinergistično. Vitamin C potencira antioksidativno učinkovitost vitamina E preko regeneracije tokoferoksilnega radikala v aktivno obliko vitamina E. Antioksidativni obrambni mehanizmi so torej medsebojno prepleteni, zato je ravnovesje med posameznimi kožnimi antioksidanti zelo pomembno. Ker oksidiran vitamin E za svoje obnavljanje troši druge antioksidante, je priporočljivo kombinirano dajanje vitamina E z antioksidantom, ki sodeluje pri njegovi obnovi, npr. vitaminom C, glutationom ali karotenoidi. Vloga nosilnega sistema pri dostavi antioksidantov v kožo Na trgu obstaja veliko formulacij z antioksidanti, najpogosteje z vitamini, ki pa so vgrajeni v klasične farmacevtske oblike, saj so le-te praviloma enostavne za izdelavo in relativno poceni. Učinkovitost teh pripravkov je pogosto vprašljiva zaradi slabih fizikalno-kemijskih in biofarmacevtskih lastnosti antioksidantov, kot so nizka topnost, slaba permeabilnost in/ali visoka nestabilnost. Eden od načinov zaščite antioksidantov in izboljšane dostave na mesto delovanja je njihova vgraditev v različne koloidne nosilce: micele, mikroemulzije, nanodelce, liposome. Za doseganje ustreznih koncentracij antioksidantov v koži peroralno jemanje običajno ne zadostuje, nasprotno pa sta se dermalna dostava in kombinacija dermalne in per os dostave antioksidantov, vgrajenih v ustrezne nosilne sisteme, pokazali kot učinkoviti. V zadnjih letih so antioksidanti postali marketinški hit v kozmetični industriji. Uporabljajo se predvsem z namenom upočasnjevanja staranja kože. V tabeli 1 so navedeni nekateri primeri komercialnih izdelkov, ki vsebujejo kot aktivne učinkovine antioksidante, vgrajene v koloidne nosilne sisteme.

Ključne besede:mikroemulzije, vitamini, sproščanje, stabilnost, vitamin C, terapija, antioksidantna

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