Poly(D,L-lactide) nanoencapsulation to reduce photoinactivation of a sunscreen agent

The use of sunscreens is the 'gold standard' for protecting the skin from ultraviolet light. Octyl methoxycinnamate (OMC) is one of the most widely used UVB filter but it can act as a sensitizer or photoallergen. When exposed to sunlight, OMC can change from the primary trans-form to cis-form and the isomerization, not reversible, conducts to a reduction of the UVB filtering efficiency because the trans-form has a higher extinction coefficient. Photostability is the most important characteristic of effective sunscreens and it can be influenced by formulation ingredients and by applying technological strategies. In this work, photostability experiments, performed on emulsion-gels containing different percentages of OMC free or loaded in poly(D,L-lactide) nanoparticles, were carried out. The presence of a polymeric envelop may act to protect the active ingredient. In this study, the influence of poly(D,L-lactide) matrices on the photochemical stability of the sunscreen agent was investigated. As highlighted in this study, free OMC in different formulations has different photoisomerization degree. Moreover, a dissimilar behaviour was observed by studying different sunscreen concentrations in the same cosmetic formulation. Photostability results show a significant reduction in photoisomerization degree for formulations containing sunscreen loaded in nanoparticles, highlighting that the encapsulation is a suitable strategy to improve OMC photostability. Moreover, sun protection factor (SPF) results show that the UVB filter protective power is also maintained after encapsulation.     

No. 4Vol. 42, No. 2, pp. 102–109, 2008A novel water-based sunscreen gel using a polymer – zinc oxide composite

Conventional sunscreen products generally must strike a compromise between efficacy and product feel; the hydrophobic ingredients that provide the sun protection generally impart an unpleasant, greasy feel and the greater the SPF rating, the worse the greasy feel. We tested an idea that a water-based sunscreen gel formulation containing inorganic UV absorbers would provide an effective way to address these problems. Our goal was to find a way to disperse inorganic sunscreen materials in water and to incorporate them into a water-based gel which would provide a more pleasant product feel. After extensive research we discovered a polymer-zinc oxide composite (P-ZnO) with high UV protective effect and high dispersibility in water. In dried powdered form, P-ZnO can be easily dispersed in water. P-ZnO makes it possible to formulate a gel-type sunscreen, which is not possible using commercially available inorganic powders. The composite size of P-ZnO is about 500 nm and its structure consists of a dense aggregate of nano-ZnO having a size distribution in the 5–10 nm range and amorphous layers of poly acrylic acid coating zinc oxide to control the particle growth, block surface activity and prevent aggregation. The water-based P-ZnO sunscreen gel offers UV protection comparable to conventional products in a delivery vehicle that is much more pleasant to use.     

Photostability assessment of sunscreens. Benzylidene camphor and dibenzoylmethane derivatives

A rapid method has been developed in order to compare the photostability of several sunscreen agents incorporated in the same type of emulsion. Thin films of the different preparations were spread on quartz plates and irradiated with a solar simulator. Differences in energy distribution according to wavelengths observed with solar simulator and sun radiation were taken into account. A kinetic study of absorption properties was carried out under solar simulator irradiation. A simple calculation gave the results which would be obtained under sunlight.
This technique differentiated the reversible transformations of photoisomerizable compounds from an irreversible disappearance which resulted in a significant loss of protective power.
Applied to benzylidene camphor derivatives, this technique showed the excellent photostability of these sunscreen agents.     

Sunscreens' photochemical behaviour: in vivo evaluation by the stripping method

This study shows the influence of a water-in-oil emulsion and an oil-in-water emulsion on the photochemical behaviour of four sunscreen preparations containing various amounts of three UV filters: octyl methoxycinnamate, butyl methoxydibenzoylmethane, and 4-methylbenzylidene camphor. With the stripping method in vivo, skin-product interactions were evaluated after topical application and ultra-violet exposure. Evaluations were also made under the same operating conditions as in determining sun protection factor in vivo. Results showed that each sunscreen preparation has a particular photochemical behaviour related to filter mixture and emulsion type. When developing a sunscreen preparation the choice of the emulsion type and filters is relevant for achieving optimum efficacy and spectral stability.     

Review of sunscreen and the emergence of non-conventional absorbers and their applications in ultraviolet protection

Protection against ultraviolet (UV) radiation is the major function of sunscreen lotions and UV-protective coatings for vehicles, homes, equipment and clothing. Sunscreen formulations have been optimized to become protective over a broader spectrum of UV radiation and maintain greater photostability. They are comprised of organic and inorganic components that act as chemical and physical UV protectors, respectively. Some of the organic components are limited by their spectrum of protection and photostability. Studies using solid lipid nanoparticles, recently explored organic molecules, inorganic components and antioxidants attempt to further optimize UV protection. In this review, we examine traditional and emerging nanoparticle components and highlight novel ideas in UV protection which may provide pathways for future studies.     

J. Cosmet. Sci., 59, 263–289 (July/August 2008)True porosity measurement of hair: A new way to study hair damage mechanisms

The purpose of this study was the development of a microbiological method for the assessment of the ultraviolet (UV) screening effect of sunscreen preparations and determination of their sun protection factor. The method is based on the lethal effect of UV radiation on Escherichia coli and the protective ability of sunscreens. The time of UV exposure required for the reduction of the E. coli viable count by 90% (decimal reduction time, DRT) was used as the photoprotection assessment parameter. The method was tested by assessing the effect of selected experimental variables on the DRT. The suitability of the method as a quality control tool for sunscreen preparations was then checked by assessing the influence of selected formulation variables on the photoprotective effect of a series of o/w emulsion formulations with different compositions. The method proved valid for detecting changes in the photoprotective effect of a market sunscreen product as a result of modifying experimental conditions. It also proved valid for ranking market sunscreen products according to their UV screening effect. Equally important, the method could successfully detect changes in the photoprotective effect of sunscreen test formulations as a function of the concentration and type of the sunscreen agents.     

In vitro skin permeation of sunscreen agents from O/W emulsions

The effects of different emulsifiers on the in vitro permeation through human skin of two sunscreen agents [octylmethoxycinnamate (OMC) and butylmethoxydibenzoylmethane (BMBM)] were investigated from O/W emulsions. The test formulations were prepared using the same oil and aqueous phase ingredients and the following emulsifier and coemulsifier systems: Emulgade SE((R)) (ceteareth-12 and ceteareth-20 and cetearyl alcohol and cetyl palmitate) and glycerylmonostearate (emulsion 1); Brij 72((R)) (steareth-2), Brij 721((R)) (steareth-21) and cetearyl alcohol (emulsion 2); Phytocream((R)) (potassium palmitoyl-hydrolysed wheat protein and glyceryl stearate and cetearyl alcohol) and glycerylmonostearate (emulsion 3); Montanov 68((R)) (cetearyl glucoside and cetearyl alcohol) (emulsion 4); Xalifin-15((R)) (C(15-20) acid PEG-8 ester) and cetearyl alcohol (emulsion 5). The cumulative amount of OMC that permeated in vitro through human skin after 22 h from the formulations being tested decreased in the order 3 > 1 congruent with 4 > 5 > 2 and was about nine-fold higher from emulsion 3 compared with that from emulsion 2. As regards BMBM, no significant difference was observed as regards its skin permeation from emulsions 1, 3, 4 and 5, whereas formulation 2 allowed significantly lower amounts of BMBM to permeate the skin. In vitro release experiments of OMC and BMBM from emulsions 1-6 through cellulose acetate membranes showed that only emulsions 4 and 5 provided pseudo-first-order release rates only for OMC. The results of this study suggest that the type of emulsifying systems used to prepare an O/W emulsion may strongly affect sunscreen skin permeation from these formulations. Therefore, the vehicle effects should be carefully considered in the formulation of sunscreen products.     

Skin penetration and stabilization of formulations containing microfine titanium dioxide as physical UV filter

Microfine titanium dioxide (TiO(2)) has become a frequently used physical UV filter in sunscreen formulations. Penetration of microfine TiO(2) into human skin seems to be possible because of the mean particle size of 20 nm. The small particle size results in a high surface activity of the primary particles and causes a formation of agglomerates in the formulation. The aim of this study was to investigate the in vivo and in vitro penetration behaviour of the physical UV filter into human skin. Furthermore, a stable sunscreen formulation with microfine TiO(2) which does not penetrate into the skin should be developed. According to our experiments, microfine TiO(2) penetrates deeper into human skin from an oily dispersion than from an aqueous one. Therefore, an o/w emulsion containing the dispersed micropigment in the aqueous phase was manufactured. Microfine TiO(2) cannot penetrate into human skin from this emulsion, but the storage stability of the formulation is very low at different temperatures. The encapsulation of the micropigment into liposomes does not result in a better stability but it causes a higher penetration depth of the particles into the skin.     

Sunblocking efficiency of various TiO(2)-loaded solid lipid nanoparticle formulations(1)

In this study, titanium dioxide (TiO(2)) was incorporated into solid lipid nanoparticle (SLN) formulations using both classical and novel preparation methods. The SLNs were investigated by evaluating their stabilities and physicochemical characteristics. UV-protection abilities of formulations were investigated using in vitro Transpore and Sun To See(TM) test methods. Results have been discussed by comparing the classical SLN formulation with the novel SLN, hybrid SLN (H-SLN) and the emulsion formulations. The results showed the superiority of the H-SLN formulations compared with the classical SLN; all SLN formulations were better when compared with the emulsion formulations considering the UV protection. Incorporation of TiO(2) as a sunscreen agent into SLN formulations gives opportunity to produce stable and safe formulations with reduced amount but high UV-protection ability.     

A novel sunscreen system based on tocopherol acetate incorporated into solid lipid nanoparticles

Synopsis Solid lipid nanoparticles (SLN) have been introduced as a novel carrier system for drugs and cosmetics. It has been found that SLN possess characteristics of physical UV-blockers on their own, thus offering the possibility of developing a more effective sunscreen system with reduced side-effects. Incorporation of the chemical sunscreen tocopherol acetate into SLN prevents chemical degradation and increases the UV-blocking capacity. Aqueous SLN dispersions were produced and incorporated into gels, followed by particle size examination, stability testing upon storage and thermoanalytical examination. Investigation of the UV-blocking capacity using different in vitro techniques revealed that the SLN dispersions produced in this study are at least twice as effective as their reference emulsions (conventional emulsions with identical lipid content). Placebo SLN even show greater UV-blocking efficacy than emulsions containing tocopherol acetate as the molecular sunscreen. Incorporation of tocopherol acetate into SLN leads to an overadditive UV-blocking effect. Furthermore, film formation of SLN on the skin and occlusivity were examined. The obtained data show that incorporation of tocopherol acetate into SLN leads to an improved sunscreen and skin care formulation.     

Poly (DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped trans-cinnamaldehyde and eugenol for antimicrobial delivery applications

Eugenol and trans-cinnamaldehyde are natural compounds known to be highly effective antimicrobials; however, both are hydrophobic molecules, a limitation to their use within the food industry. The goal of this study was to synthesize spherical poly (DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped eugenol and trans-cinnamaldehyde for future antimicrobial delivery applications. The emulsion evaporation method was used to form the nanoparticles in the presence of poly (vinyl alcohol) (PVA) as a surfactant. The inclusion of antimicrobial compounds into the PLGA nanoparticles was accomplished in the organic phase. Synthesis was followed by ultrafiltration (performed to eliminate the excess of PVA and antimicrobial compound) and freeze-drying. The nanoparticles were characterized by their shape, size, entrapment efficiency, and antimicrobial efficiency. The entrapment efficiency for eugenol and trans-cinnamaldehyde was approximately 98% and 92%, respectively. Controlled release experiments conducted in vitro at 37 °C and 100 rpm for 72 h showed an initial burst followed by a slower rate of release of the antimicrobial entrapped inside the PLGA matrix. All loaded nanoparticles formulations proved to be efficient in inhibiting growth of Salmonella spp. (Gram-negative bacterium) and Listeria spp. (Gram-positive bacterium) with concentrations ranging from 20 to 10 mg/mL. Results suggest that the application of these antimicrobial nanoparticles in food systems may be effective at inhibiting specific pathogens. PRACTICAL APPLICATION: Nanoencapsulation of lipophilic antimicrobial compounds has great potential for improving the effectiveness and efficiency of delivery in food systems. This study consisted of synthesizing PLGA nanoparticles with entrapped eugenol and trans-cinnamaldehyde. By characterizing these new delivery systems, one can understand the controlled-release mechanism and antimicrobial efficiency that provides a foundation that will enable food manufacturers to design smart food systems for future delivery applications, including packaging and processing, capable of ensuring food safety to consumers.     

Multiparticulate carriers for sun‐screening agents

Many molecular sunscreens penetrate into the skin causing photo‐allergic and photo‐toxic reactions as well as skin irritations establishing an urgent need for the development of a safer sunscreen formulation. The search for active substances, efficient combinations, and the design of novel vehicles or carriers has led to the implementation of new cosmetic systems in contrast to the classic forms such as creams or gels. Amongst various approaches utilized to improve performance of sunscreening agents, the use of multiparticulate delivery systems is gaining increasing attention amongst researchers. Multiparticulate delivery systems can be incorporated into gels, creams, liquids, powders or other formulations, and can release active agents depending on their temperature, moisture, friction, volatility of the entrapped ingredients or time. These systems also have the ability of scattering or reflecting incoming UV radiations and therefore can act as physical sunscreens on their own.     

Nanostructured lipid carriers as novel carrier for sunscreen formulations

Incorporation of sunscreens into lipid carriers with an increased sun protection factor (SPF) has not yet been fully accomplished. In the present paper, the effectiveness of a sunscreen mixture, incorporated into the novel topical delivery systems, i.e. solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), used as ultraviolet (UV) protector enhancers with a distinctly higher loading capacity has been developed and evaluated. SLN and NLC were produced by hot high pressure homogenization technique in lab scale production. Size distribution and storage stability of formulations were investigated by laser diffractometry and photon correlation spectroscopy. Nanoparticles were characterized by their melting and recrystallization behaviour recorded by differential scanning calorimetry. Lipid nanoparticles produced with a solid matrix (SLN and NLC) were established as a UV protection system. The loading capacities for molecular sunscreens reported before now were in the range of 10-15%. It was possible to load NLC with up to 70% with molecular sunscreen, which is appropriate to obtain high SPFs with this novel UV protection system. The developed formulations provide a beneficial alternative to conventional sunscreen formulations. The UV protective efficacy of the lipid particles varied with the nature of lipid and UV wavelength.     

Olive oil-in-water emulsions stabilized with caseinate: Elucidation of protein–lipid interactions by infrared spectroscopy

This paper reports a FT-IR study for probing lipid and protein structural changes and their interactions in various oil-in-water emulsions. Two different emulsions were prepared using sodium caseinate, as stabilizer system, without and with microbial transglutaminase (MTG), denominated E/SC and E/SC + MTG respectively. Proximate composition, fat and water binding properties and textural characteristics were also evaluated in the emulsions. Penetration force and gel strength values were used to distinguish different (P < 0.05) textural behaviours depending on the formulation of emulsifying system. E/SC + MTG emulsion showed gel textural behaviour while E/SC lack of this property. The spectral results showed frequency upshifting of the amide I band in going from protein stabilizer systems isolate (the solution used as reference) to their corresponding emulsions, what is attributable to greater protein structural order upon emulsion formation. Enzymatic action of MTG in the sodium caseinate stabilizing system induces structural changes, in terms of lipid chain disorder or lipid–protein interactions and protein secondary modifications, which may reflect the formation of a gel structure in the emulsion. These results could help to choose the stabilizing system that is most suitable and effective for its use in the formulation of food products.     

In vitro assessment of sunscreen photostability: the effect of radiation source, sunscreen application thickness and substrate

The photostabilities of four sunscreen products have been assessed in vitro by applying sunscreen to a substrate and measuring the spectral transmission prior to, and after exposure to a source of ultraviolet (UV) radiation. Results were independent of whether an application thickness of 1 or 2 mg/cm ; 2 was used, and whether the UV source was natural sunlight or a xenon arc solar-simulator. There were significant differences, however, between results obtained on a roughened quartz substrate and those obtained on excised human epidermis. It is unlikely that any substrate will give an exact representation of the in vivo situation and, indeed, both quartz and excised human epidermis have disadvantages associated with their use. However, the ranking of the four products in terms of their photostability was the same for both substrates. This implies that transmission spectroscopy, with either a quartz or a human epidermis substrate, can be used successfully to compare the photostabilities of different sunscreen products.     

Beyond sun protection factor testing

Ultraviolet radiation in sunlight produces a range of acute and chronic adverse effects on the skin including sunburn, photosensitivity rashes, immunosuppression, photoageing and carcinogenesis. Sunscreens aim to provide protection, but standard testing procedures primarily involve assessment of ability to protect against acute erythema, as evidenced by the sun protection factor (SPF). The SPF may correlate poorly with other aspects of protection, particularly since ultraviolet A is weakly erythemogenic compared with ultraviolet B, yet may make a greater contribution to certain other skin effects of sunlight. Nevertheless, there is an increasing tendency for the sunscreen industry to make claims for their products beyond the SPF data. There is a need to develop systems for clinical testing of sunscreens against other endpoints caused by ultraviolet exposure of skin, including immunosuppression and photosensitivity rashes. In particular, there is a largely unrecognized need for testing of sunscreens against the condition known as polymorphic light eruption, a photosensitivity disorder estimated to affect a staggering 10-20% of the population in the northern hemisphere. Ultimately, protection of the skin by sunscreens can only be as effective as their adequacy of application to the skin surface in the everyday setting permits. Optimal sunscreen formulation, and public and patient education in appropriate application technique, both make vital contributions to efficacy of sunscreen protection. This article focuses on the need for extended clinical testing of sunscreens, with particular reference to the photosensitivity disorders, and for improvements in sunscreen formulation and in the adequacy of sunscreen application to the skin surface.     

Transparent gels: study of their formation and assimilation of active ingredients through phase diagrams

Multicomponent gel formulations capable of assimilating, simultaneously, several active ingredients of potential application in the cosmetic field were studied.
The possibility of formation of a transparent gel was determined using a method which consisted in the optimization of several lipophilic basic compositions, composed of oil, a mixture of surfactants, a sunscreen agent, several vitamins and antioxidants situated in the base of a regular tetrahedron that symbolized the considered system. To this, a polar phase made of water, a cosolvent and urea in appropriate proportions and situated in the fourth vertex, was progressively added.
It may be concluded, that the use of phase diagrams on cosmetic systems, constitutes a useful way to select the components and their mutual ratios, allowing an adaptation to the specific requested conditions of formulation.     

J. Cosmet. Sci., 59, 385–398 (September/October 2008)Evaluation of liposomal and conventional formulations of octyl methoxycinnamate on human percutaneous absorption using the stripping method

The objective of this study was to determine the influence of vehicles on the penetration of octyl methoxycinnamate (OMC), as a UV absorber, to the stratum corneum by the stripping method. The experimental formulations consisted of a conventional o/w emulsion and multilamellar and small unilamellar liposomes (MLVs and SUVs) containing OMC. MLVs containing OMC were prepared by the fusion method and then converted to SUVs by probe sonication. Various formulations were then applied onto the midvolar forearms of six volunteers at a dose of 2 mg cm^-2. After determined timepoints, the stripping method was conducted whereby 22 tape strips were applied and subsequently divided into different stripping groups. The sunscreen agent was assessed by HPLC while the SPF (sun protection factor) of the formulations was determined in human volunteers in accordance with the Australian standard. Overall the results indicate that skin accumulation of OMC in MLVs was significantly greater than in the o/w emulsion and SUVs. Furthermore, SUV's penetration into the deeper skin layers was significantly greater than MLV's and that of a conventional o/w emulsion. Also, higher amounts of OMC were recovered from the upper layers of the stratum corneum than from the deeper layers in all the formulations tested. Finally, the SPF of the liposomes containing OMC was slightly greater than that of the control lotions at a similar concentration of OMC. In conclusion, the result of this study indicates that an MLV prepared by the fusion method could be a better vehicle for OMC as a sunscreen since it has a slightly better SPF compared to a conventional formulation and more remains in the stratum corneum, reducing its penetration to the deeper layers.
Address all correspondence to M. R. Jaafari.     

Antimicrobial Efficacy of Poly (DL‐lactide‐co‐glycolide) (PLGA) Nanoparticles with Entrapped Cinnamon Bark Extract against Listeria monocytogenes and Salmonella typhimurium

Nanoencapsulation of active compounds using poly‐(d,l ‐lactide‐co‐glycolide) (PLGA) is commonly used in the pharmaceutical industry for drug delivery and may have important applications in the food industry. Control of growth of foodborne bacteria with the goals of reducing the number of foodborne illness outbreaks, assuring consumers a safer food supply remains a priority in the food industry. Natural antimicrobials are an excellent way to eliminate pathogens without introducing chemical preservatives that consumers may find undesirable. Cinnamon bark extract (CBE) is an effective pathogen inhibitor isolated from cinnamon spice. PLGA nanoparticles containing CBE were produced using an emulsion‐solvent evaporation method and characterized for size, polydispersity, morphology, entrapment efficiency, in vitro release and pathogen inhibition. PLGA with 2 different ratios of lactide to glycolide (65:35 and 50:50) were used to determine how polymer composition affected nanoparticle characteristics and antimicrobial potency. The size of the nanoparticles ranged from 144.77 to 166.65 nm and the entrapment efficiencies of CBE in 65:35 PLGA and 50:50 PLGA were 38.90% and 47.60%, respectively. The in vitro release profile at 35 °C showed an initial burst effect for both types of PLGA followed by a more gradual release of CBE from the polymer matrix. Both types of PLGA nanoparticles loaded with CBE were effective inhibitors of Salmonella enterica serovar Typhimurium and Listeria monocytogenes after 24 and 72 h at concentrations ranging from 224.42 to 549.23 μg/mL. The PLGA encapsulation improved delivery of hydrophobic antimicrobial to the pathogens in aqueous media.     

Membrane Structured Solid Nanoparticles – A Novel Nanotechnology for Delivery of Cosmetic Active Ingredients

Lipid nanoparticles have a structure similar to that of nanoemulsions. Their size ranges typically from 50 to 1000 nm. They differ from nanoemulsions in that the lipid core is a solid. The matrix consists of solid lipids or mixtures of lipids. Over the past years it has been demonstrated that solid lipid nanoparticles appear to be a promising drug carrier system for the future. Their occlusion properties reduce transepidermal water loss and can enhance penetration of active ingredients through the stratum corneum. As with all new technologies, some problems with the solid lipid nanoparticle technology need to be solved. One major problem is the homogeneous incorporation of amphiphilic active ingredients into the crystal matrix of the nanoparticles. Actives with an amphiphilic character like tocopherol or retinol cannot be kept homogeneously distributed in the wax structure during the emulsification process. Due to their hydrophilic head group they accumulate at the exterior layer of the nanoparticles together with the surfactant system used. Consequently, homogeneous release over time is not guaranteed and a burst release has to be expected. A second disadvantage is the manufacturing process. Solid lipid nanoparticles can be produced only under high pressure conditions. Also the concentration of the solid particles in the dispersion, which is added to an emulsion, is quite low. To overcome these problems membrane structured solid nanoparticles (MSSN) have been developed. These MSSN systems consist of liquid crystalline membrane systems with extremely low surfactant concentrations. The lateral movement of actives is controlled by amphiphilic solid actives such as ceramides and solid emollients. This guarantees maintenance of the advantageous properties of solid lipid nanoparticles such as retarded release of actives and their protection against chemical decomposition, but it also allows the homogeneous incorporation of amphiphilic actives. Membrane structured solid nanoparticles are produced using a continuous three‐phase emulsification technique. This allows protection of heat‐sensitive actives against decomposition. The concentration of nanoparticles in the MSSN dispersion can be kept higher than 60% (w/w). Even at these concentrations the nanodispersions keep their flow properties. As a result, they can be easily incorporated into the final formulation.