Aging can be described as an extremely complex occurrence from which no organism can be excluded. Intrinsic and extrinsic aging make out the two components of skin aging and they differ on the macromolecular level while sharing specific molecular characteristics which include elevated levels of reactive oxygen species (ROS) and matrix metalloproteinase (MMP) while collagen synthesis decreases. The skin functions as a protective barrier against the harsh environment and is essential for regulating body temperature. The stratum corneum (SC) is responsible for the main resistance to the penetration of most compounds; nevertheless the skin represents as an appropriate target for delivery. The target site for anti-aging treatment includes the epidermal and dermal layers of the skin. Calendula oil and L-carnitine L-tartrate was utilised as the cosmeceutical actives as they can be classified as a mixed category of compounds/products that lie between cosmetics and drugs. Both show excellent properties which can prove valuable during anti-aging treatment, whether it is due to the scavenging of ROS (calendula oil), moisturising effects (calendula oil and L-carnitine L-tartrate) or the improvement of the skin turnover rate (L-carnitine L-tartrate). The Pheroid™ delivery system can enhance the absorption of a selection of active ingredients. The aim of this study was to determine whether the Pheroid™ delivery system will enhance the flux and/or delivery of the named actives to the target site by performing Franz cell diffusion studies over an 8 h period, followed by tape stripping experiments. The Pheroid™ results of the actives were compared to the results obtained when 1 00 % calendula oil was applied and the L-carnitine L-tartrate was dissolved in phosphate buffer solution (PBS), respectively. In the case of calendula oil only a qualitative gas chromatography mass spectrometry (GC/MS) method could be employed. No calendula oil was observed to permeate through the skin, but linoleic acid (marker compound) was present in the epidermis and dermis layers. Components in the Pheroid™ delivery system hampered the results as the marker compound identified is a fundamental component of the Pheroid™, making it difficult to determine whether or not the Pheroid™ delivery system enhanced calendula oil's penetration. The aqueous solubility and log D partition coefficient of L-carnitine L-tartrate was determined. Inspection of the log D value of -1.35 indicated that the compound is unfavourable to penetrate the skin, whereas the aqueous solubility of 16.63 mg/ml in PBS at a temperature of 32º C indicated favourable penetration. During the Franz cell diffusion and tape stripping studies it was determined by liquid chromatography mass spectrometry (LC/MS) that carnitine may be inherent to human skin. Pheroid™ enhanced the flux (average of 0.0361 µg/cm2.h, median of 0.0393 µg/cm2.h) of the L-carnitine L-tartrate when compared to PBS (average of 0.0180 µg/cm2.h, median of 0.0142 µg/cm2.h ) for the time interval of 2 -8 h. The PBS was more effective in delivering the active to the target site (0.270 µg/ml in the epidermis and 2.403 µg/ml in the dermis) than Pheroid™ (0.111 µg/ml and 1.641 µg/ml in the epidermis and dermis respectively). Confocal laser scanning microscopy (CLSM) confirmed the entrapment of L-carnitine L-tartrate in the Pheroid™ vesicle, while in the case of calendula oil it was impossible to differentiate between the oil and the Pheroid™ components. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2009.

A administração oral de isotretinoína (IST) é eficaz no tratamento da acne; no entanto, seu uso está associado a efeitos adversos, como ressecamento da pele, epistaxe, distúrbios imunológicos e psiquiátricos, enquanto a eficácia da aplicação tópica é prejudicada pela intensa irritação causada na pele. Proteger a IST do contato direto com a pele e direcionar sua liberação para os folículos pilosos, local onde a acne se desenvolve, pode reduzir a irritação e aumentar a eficácia do tratamento. O polímero Delonix (DLX), galactomanano natural derivado da semente de Delonix regia, pode ser manipulado para produzir nanopartículas para a liberação direcionada de IST na pele. Desta forma, o objetivo deste estudo foi desenvolver nanopartículas poliméricas de DLX (IST-DLX) contendo IST e avaliar seu potencial para o tratamento tópico da acne. O DLX foi coletado, purificado e caracterizado quanto a composição de monossacarídeos e massa molecular (MM). Nanopartículas DLX sem IST (branco), nanopartículas fluorescentes de DLX (nanopartículas contendo BODIPY (BOD-DLX)) e nanopartículas IST-DLX foram preparadas e caracterizadas por tamanho, índice de polidispersividade (PdI), potencial zeta (pz) e eficiência de encapsulação (EE). O estudo de liberação in vitro das nanopartículas IST-DLX foi realizado utilizando células de difusão e membrana sintética, enquanto a penetração cutânea das nanopartículas BOD-DLX e IST-DLX foi avaliada por microscopia confocal e tape stripping diferencial em pele de orelha de porco dermatomizada, respectivamente. A influência das nanopartículas IST-DLX na modulação de IL-6, IL-10 e TNF-? foi avaliada in vitro utilizando células de macrófagos AMJ-2 estimuladas com lipopolisacarídeos (LPS) e a atividade antimicrobiana foi avaliada em meio de cultura de Propionibacterium acnes. In vivo, as nanopartículas IST-DLX foram avaliadas quanto a penetração e irritação cutânea em ratos Wistar (protocolo de aprovação CEUA-FCFRP nº 17.5.213.60.3). A MM do polímero DLX foi de ~177 kDa, contendo predominantemente manose e galactose na proporção de 6,3:1. O tamanho das nanopartículas IST-DLX, determinado por dispersão de luz, foi entre 215 a 232 nm, PdI < 0,2, pz < -30 mV e EE > 25%. As nanopartículas IST-DLX sustentaram a liberação da IST, com cerca de 37% de IST sendo liberado em 48 h. As imagens de microscopia confocal mostraram que as nanopartículas BOD-DLX concentraram-se na epiderme e nos folículos pilosos em comparação com a solução de BODIPY livre, a qual permeou até a derme. Foi observada uma penetração de IST significativamente maior e descontrolada em todas as camadas da pele de orelha de porco quando a solução de polímero de IST-DLX foi usada em comparação com um acúmulo de IST menor e controlado quando as nanopartículas IST-DLX foram aplicadas. As nanopartículas IST-DLX direcionaram a IST para os folículos pilosos (26%) em comparação com a solução de IST (6,5%) que permeou por todas as camadas da pele. As nanopartículas IST-DLX reduziram significativamente a produção de IL-6 em células de macrófagos estimuladas por LPS, mesmo após 48 h, em comparação com a solução de IST livre, que reduziu significativamente a produção de IL-6 apenas até 24 h. Tanto as nanopartículas ISTDLX quanto a solução de IST livre não inibiram o crescimento de P. acnes. Não foi observado nenhum sinal de eritema nos ratos tratados com nanopartículas IST-DLX, com ou sem irradiação UVA, enquanto os tratados com solução de IST apresentaram eritema. A espessura da epiderme dos ratos tratados com as nanopartículas foi significativamente menor do que daqueles tratados com IST livre, com ou sem irradiação UVA. Conclui-se que as nanopartículas IST-DLX direcionam e sustentam a liberação de IST na pele em concentrações ótimas, modulam a resposta inflamatória da IL-6 e previnem o eritema inflamatório relacionado ao IST in vivo. Sendo assim, o polímero DLX pode ser considerado um polímero promissor para a liberação sustentada e direcionada de fármacos. / Oral isotretinoin (IST) has been effective in acne treatment; however, its use is associated with side effects such as skin dryness, epistaxis, immune disorder and psychiatric concerns while its topical gel application\'s effectiveness is hampered by irritancy. Protecting IST from direct skin contact and targeting its release to the hair follicles where the acne develops can reduce irritation and increase the effectiveness of treatment. Delonix (DLX) polymer is a natural galactomannan derived from Delonix regia seed that may be engineered to yield nanoparticles for IST skin targeting. Therefore, the aim of this study was to develop IST-loaded DLX (IST-DLX) polymeric nanoparticles and assess its skin targeting prospects for acne treatment. DLX was collected, purified and characterized by monosaccharide composition and molecular weight (Mw). Blank DLX nanoparticles, fluorescent DLX nanoparticles (BODIPY-loaded (BOD-DLX) nanoparticles) and IST-DLX nanoparticles were prepared and characterized by size, polydispersibility index (PdI), zeta potential (zp) and encapsulation efficiency (EE). In vitro release study of IST-DLX nanoparticles was performed using diffusion cells and synthetic membrane, while skin targeting of BOD-DLX and IST-DLX nanoparticles were assessed by confocal microscopy and differential tape stripping technique in dermatomed pig ear skin respectively. IST-DLX polymeric nanoparticles\' IL-6, IL-10 and TNF-? modulation was assessed in vitro using lipopolysaccharide (LPS) stimulated AMJ-2 macrophage cells and antimicrobial activity was assessed in Propionibacterium acnes culture medium. IST-DLX nanoparticles\' skin penetration and irritation were evaluated in vivo in Wistar rats (ethics committee approval protocol CEUA-FCFRP nº 17.5.213.60.3). DLX polymer Mw was ~177 kDa, containing predominantly mannose and galactose in ratio 6.3:1. IST-DLX nanoparticles\' size determined by light scattering was between 215 to 232 nm, PdI < 0.2, zp < -30 mV, EE > 25 %. IST-DLX nanoparticles sustained IST release, with about 37% IST being released in 48 h. Confocal images showed that BOD-DLX nanoparticles accumulated in the epidermis and hair follicles as compared to free BODIPY solution which permeated into the dermis. Significantly higher and uncontrolled IST penetration into all layers of pig ear skin with IST-DLX polymer solution was observed as compared to lower, controlled but optimum IST accumulation into the pig ear skin when IST-DLX nanoparticles were used. IST-DLX nanoparticles targeted the hair follicle (26 %) as compared to IST solution (6.5 %) which permeated through all skin layers. IST-DLX polymeric nanoparticles significantly reduced IL-6 production in LPS stimulated macrophage cells at 48 h as compared to free IST solution which significantly reduced IL-6 production only at 24 h. Both IST-DLX nanoparticles and free IST solution did not inhibit P. acnes growth. No sign of inflammatory erythema was observed in IST-DLX nanoparticles treated Wistar rats with or without UVA irradiation as compared to free IST treated ones. Epidermal thickness of rats treated with IST-DLX nanoparticles was significantly smaller than those treated with free IST with or without UVA irradiation. It can be concluded that IST-DLX nanoparticles can target, deliver and sustain IST release to the skin at optimum concentrations, modulate IL-6 inflammatory responses and may prevent IST related inflammatory erythema in vivo. DLX polymer could be promising polymer for drug delivery.

No description available.

The available literature indicates that to date, few research has been performed on oil powders for topical delivery. The aim of this project was to investigate the release characteristics of oil powder formulations, as well as their dermal and transdermal delivery properties. Whey protein-stabilised emulsions were used to develop oil powders. Whey protein was used alone, or in combination with chitosan or carrageenan. Nine oil powders, with salicylic acid as the active ingredient, were formulated by using the layer-by-layer method. Three different pH values (pH 4, 5 and 6) were used to prepare the formulations, because of the different charges that polymeric emulsifiers may have. The characteristics of the prepared oil powders were determined, including their droplet sizes, particle size distributions, loss on drying, encapsulation efficiencies, oil leakage and water dispersibility. Release studies (membrane diffusion studies) were conducted by utilising cellulose acetate membranes (0.2 μm pore size) and Franz-type diffusion cells over a period of eight hours. The release of the active ingredient was determined for all nine powders, their respective template emulsions, as well as their respective oil powders redispersed in water. The release of salicylic acid from the respective redispersed oil powders was then further compared to its release from the template emulsions and from the oil powders. The effect of pH and different polymer types used in preparing the oil powders, their respective redispersed oil powders and the template emulsions were determined with regards to the release of the active ingredient from all these preparations. The effect of pH and different polymers used was furthermore determined on the oil powders and their respective redispersed oil powders, with regards to their dermal and transdermal deliveries. Transdermal delivery and skin uptake were investigated on specifically selected powders only, based on the outcomes of the oil powder characterisation and release data. The qualifying formulations were chitosan pH 4, 5 and 6, whey and carrageenan pH 6 oil powders, together with their respective redispersed oil powders in water. Human abdominal skin was dermatomed (thickness 400 μm) for use in the diffusion studies. Franz-type diffusion cells were used over a period of 24 hours. The results of the membrane release studies indicated that the oil powders had achieved a significantly higher release than their respective redispersed oil powders. The release of salicylic acid from the redispersed oil powders and from their respective emulsions was similar. The transdermal delivery test outcomes showed that the effect of pH could have been influenced by the degree of ionisation, resulting in a decrease in permeation with increasing ionisation of salicylic acid, in accordance with the pH partition hypothesis. Furthermore, biopolymers, such as chitosan had demonstrated a penetration enhancing effect, which had led to the enhanced dermal and transdermal delivery of salicylic acid. A correlation was also found between the powder particle size and transdermal delivery. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

The available literature indicates that to date, few research has been performed on oil powders for topical delivery. The aim of this project was to investigate the release characteristics of oil powder formulations, as well as their dermal and transdermal delivery properties. Whey protein-stabilised emulsions were used to develop oil powders. Whey protein was used alone, or in combination with chitosan or carrageenan. Nine oil powders, with salicylic acid as the active ingredient, were formulated by using the layer-by-layer method. Three different pH values (pH 4, 5 and 6) were used to prepare the formulations, because of the different charges that polymeric emulsifiers may have. The characteristics of the prepared oil powders were determined, including their droplet sizes, particle size distributions, loss on drying, encapsulation efficiencies, oil leakage and water dispersibility. Release studies (membrane diffusion studies) were conducted by utilising cellulose acetate membranes (0.2 μm pore size) and Franz-type diffusion cells over a period of eight hours. The release of the active ingredient was determined for all nine powders, their respective template emulsions, as well as their respective oil powders redispersed in water. The release of salicylic acid from the respective redispersed oil powders was then further compared to its release from the template emulsions and from the oil powders. The effect of pH and different polymer types used in preparing the oil powders, their respective redispersed oil powders and the template emulsions were determined with regards to the release of the active ingredient from all these preparations. The effect of pH and different polymers used was furthermore determined on the oil powders and their respective redispersed oil powders, with regards to their dermal and transdermal deliveries. Transdermal delivery and skin uptake were investigated on specifically selected powders only, based on the outcomes of the oil powder characterisation and release data. The qualifying formulations were chitosan pH 4, 5 and 6, whey and carrageenan pH 6 oil powders, together with their respective redispersed oil powders in water. Human abdominal skin was dermatomed (thickness 400 μm) for use in the diffusion studies. Franz-type diffusion cells were used over a period of 24 hours. The results of the membrane release studies indicated that the oil powders had achieved a significantly higher release than their respective redispersed oil powders. The release of salicylic acid from the redispersed oil powders and from their respective emulsions was similar. The transdermal delivery test outcomes showed that the effect of pH could have been influenced by the degree of ionisation, resulting in a decrease in permeation with increasing ionisation of salicylic acid, in accordance with the pH partition hypothesis. Furthermore, biopolymers, such as chitosan had demonstrated a penetration enhancing effect, which had led to the enhanced dermal and transdermal delivery of salicylic acid. A correlation was also found between the powder particle size and transdermal delivery. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2014

Pigmentation disorders occur in multiple conditions (Hakozaki et al., 2006:105). Although many modalities of treatments are available, none are completely satisfactory (Briganti et al., 2003:101). Two cytokines normally present in the skin, transforming growth factor–beta1 (TGF–81) and tumour necrosis factor–alpha (TNF–9), have been shown to inhibit melanin synthesis (Martinez–Esparza, 2001:972). The stratum corneum has been commonly accepted as the main barrier to percutaneous absorption. Many techniques have been applied to overcome this barrier properties and to enhance penetration with varying success (Pellet et al., 1997:92). The objective of this study was to investigate the topical delivery of the above mentioned peptide drugs with aid of the Pheroid drug delivery system. Pheroid technology is a delivery system that promotes the absorption and increases the efficacy of dermatological, biological and oral medicines in various pharmacological groups (Grobler et al., 2008:4). Pheroid entraps drugs with high efficiency and delivers them with remarkable speed to target sites (Grobler, 2004:4). In order to avoid degradation of these peptides, bestatin hydrochloride (an aminopeptidase inhibitor), was used (Lkhagvaa et al., 2008:386). Topical drug delivery was achieved by means of vertical Franz cell diffusion studies performed over a 6 and 12 h period. ELISA (enzyme linked immunosorbent assay) detection was used to detect cytokine concentrations. Entrapped cytokine solutions were monitored by confocal laser scanning microscopy (CLSM). Upon removal of donor and receptor compartments, skin discs were subjected to tape stripping in order to establish the amount of active present within the stratum corneum and epidermis as well as the remaining dermis (Pellet et al., 1997:92). When comparing the two studies with each other, it is evident that the diffused concentration values obtained with PBS (phosphate buffer solution, pH 7.4) was lower than that obtained with the Pheroid drug delivery system. Both cytokine concentrations were successfully delivered topically as a minimum of concentrations for both actives were detected. This positive result was confirmed as well by the amount of active detected in stratum corneum–epidermis and epidermis–dermis solutions. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2011.

Pigmentation disorders occur in multiple conditions (Hakozaki et al., 2006:105). Although many modalities of treatments are available, none are completely satisfactory (Briganti et al., 2003:101). Two cytokines normally present in the skin, transforming growth factor–beta1 (TGF–81) and tumour necrosis factor–alpha (TNF–9), have been shown to inhibit melanin synthesis (Martinez–Esparza, 2001:972). The stratum corneum has been commonly accepted as the main barrier to percutaneous absorption. Many techniques have been applied to overcome this barrier properties and to enhance penetration with varying success (Pellet et al., 1997:92). The objective of this study was to investigate the topical delivery of the above mentioned peptide drugs with aid of the Pheroid drug delivery system. Pheroid technology is a delivery system that promotes the absorption and increases the efficacy of dermatological, biological and oral medicines in various pharmacological groups (Grobler et al., 2008:4). Pheroid entraps drugs with high efficiency and delivers them with remarkable speed to target sites (Grobler, 2004:4). In order to avoid degradation of these peptides, bestatin hydrochloride (an aminopeptidase inhibitor), was used (Lkhagvaa et al., 2008:386). Topical drug delivery was achieved by means of vertical Franz cell diffusion studies performed over a 6 and 12 h period. ELISA (enzyme linked immunosorbent assay) detection was used to detect cytokine concentrations. Entrapped cytokine solutions were monitored by confocal laser scanning microscopy (CLSM). Upon removal of donor and receptor compartments, skin discs were subjected to tape stripping in order to establish the amount of active present within the stratum corneum and epidermis as well as the remaining dermis (Pellet et al., 1997:92). When comparing the two studies with each other, it is evident that the diffused concentration values obtained with PBS (phosphate buffer solution, pH 7.4) was lower than that obtained with the Pheroid drug delivery system. Both cytokine concentrations were successfully delivered topically as a minimum of concentrations for both actives were detected. This positive result was confirmed as well by the amount of active detected in stratum corneum–epidermis and epidermis–dermis solutions. / Thesis (M.Sc. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2011.