Hot High Pressure Homogenization Research Articles

Development of a nanoemulsion of Phyllanthus emblica L. branch extract

For potential topical administration, we formulated a nanoemulsion containing phenolic constituents of Phyllanthus emblica branch extract. The nanoemulsion has high entrapment efficiency, small particle size, is stable, and can release its main chemical components. Branches of P. emblica were extracted with 50% ethanol (EPE) with 5.4% yield. HPLC analysis indicated several phenolic compounds, including gallic acid, vanillic acid, epigallocatechin (EGC), epigallocatechin gallate (EGCG) and ellagic acid. These were selected as chemical markers of EPE in the nanoemulsion development. The nanoemulsion was prepared by microemulsion techniques with hot high pressure homogenization. A ternary phase diagram was constructed to obtain the optimized nanoemulsion. The obtained transparent EPE nanoemulsion is composed of isopropyl myristate (0.6% w/w), Brij® 78 (0.35% w/w), and 0.15% (w/w) EPE. The optimized EPE nanoemulsion had a median particle size of 191.63 ± 4.07 nm with a narrow particle size distribution, a zeta potential of −10.19 ± 0.54 mV, high entrapment efficiency at 67.99 ± 0.87% and good stability at 4 °C after 90 d of storage. The release of active ingredients from the EPE nanoemulsion was slower than that of the EPE aqueous formulation. The loading ratios of the five phenolic compounds were high, with relative order of EGC > EGCG > vanillic acid > gallic acid > ellagic acid, resulting in slow release profiles of EGC and EGCG in the EPE nanoemulsion. In conclusion, the obtained EPE nanoemulsion has good characteristics for future clinical trials.

Targeting of coenzyme Q10 via d-alpha-tocopheryl polyethylene glycol 1000 succinate-based nanoemulsion to the heart

d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), a water-soluble derivative of natural vitamin E, has been intensively used in drug delivery systems. TPGS (CoQ10-NE-TPGS) and lecithin-based (CoQ10-NE-LC) coenzyme Q10-loaded nanoemulsions were prepared by hot high-pressure homogenization (HPH) and tested for their ability to target heart tissue. Both formulations yielded particles ~50nm in diameter. CoQ10 in both the formulations was in a supercooled melt state without crystallization. CoQ10-NE-TPGS more effectively delivered CoQ10 to heart tissue than CoQ10-NE-LC after intravenous administration. CoQ10 concentration in the heart was 2.8-fold higher at 5min after intravenous administration of CoQ10-NE-TPGS compared to CoQ10-NE-LC. Higher tissue levels were maintained for 90min after injection. These data suggest that CoQ10-NE-TPGS could be a potential vehicle for rapid delivery of CoQ10 to heart tissue.

Enhanced photoprotection for photo-labile compounds using double-layer coated corn oil-nanoemulsions with chitosan and lignosulfonate

With the aim to establish a novel nanocarrier system with relatively high payload and high photoprotection capacity for photo-labile active compounds, in this work, deltamethrin (photo-labile compound) was encapsulated into corn oil-nanoemulsions (NE) by a hot high pressure homogenization technique followed by coating with chitosan as the first coating layer (CH-NE) and lignosulfonate as the second coating layer to form a double-layer coated NE (L-CH-NE). The optimal conditions for preparation of NE, chitosan coating and lignosulfonate coating were investigated. The results indicate that polymer coating and the number of coating layers significantly affected the release profile and photoprotection capacity of nanocarriers. In particular, after coating, the release rate became slower and photoprotection capacity became higher. Moreover, in the case of L-CH-NE after 24h of UV exposure in direct photolysis and 2.5h of UV exposure in indirect photolysis, the non-degraded amount of deltamethrin was approximately 4.5 times and 2.1 times, respectively, higher than that of the free-from deltamethrin. In the future, this novel nanocarrier system will show great potential and be widely applied to many fields related to protection of photo-labile compounds against photo-degradation.

Preparation and Characterization of Broad-Spectrum Sunscreens Loaded Nanostructured Lipid Carrier

A comprehensive photoprotective formulation was developed to enhance photoprotection ,compared to a conventional nanoemulsion ,having the concentration of two new molecular sunscreens, namely Diethylamino hydyoxybenzoyl hexyl benzoate(Uvinul ® A Plus) and Ethylhexyl triazone(Uvinul® T 150). In the present paper, the sunscreen mixture was incorporated into nanostructured lipid carriers (NLCs). After the production by hot high pressure homogenization, the NLC were analyzed in terms of particle size, physical state, particle shape, ultraviolet absorbance and stability. The particle size for all NLC was around 100-900 nm after production. The determination of 2 organic UV filters was performed by HPLC with UV spectrophotometric detection. The loading capacities for molecular sunscreens was up to 30%. In the sunlight, the retention rate of Uvinul ® A Plus and Uvinul ® T150 was still up to 80% after three months .

Design and Evaluation of Miconazole Nitrate loaded Nanostructured Lipid Carriers (NLC) for improving the Antifungal therapy

The aim of this study was to prepare and evaluate gels incorporating nanostructured lipid carriers (NLC) of Miconazole nitrate (MN) for systemic delivery of the active after topical application. MN has been used as model drugs to be incorporated into nanostructured lipid carriers, once they are very well established as antimycotics for the treatment of topical fungal infections. NLC designed for topical administration of MN, were prepared by the hot high pressure homogenization technique. This MN-NLC was characterized for particle size, entrapment efficiency, and SEM. The lipid nanoparticles were incorporated in gels for convenient topical application and were evaluated forfor particle size, Rheological analysis Texture analysis , In vitro drug release studies and Ex Vitro skin permeation Studies. The preparation of aqueous NLC dispersions with a mean particle size lower than 300 nm has been obtained with uniform size distribution (PI < 0.350). The prepared semi-solid systems showed mean particle size remained lower than 250 nm and PI remained lower than 0.500 after 3 months of storage. An initial rapid release was observed in the case of Marketed gel, whereas MN- NLC Gel depicted a slow initial release with a lag time of 0.5 h and 1 h, respectively. High amount of MN release was facilitated through abdominal skin of rats from marketed gel than MN-NLC Gel. Research work could be concluded as successful development of MN-loaded NLC-bearing hydrogel to increase the encapsulation efficiency of colloidal lipid carriers with advantage of improved performance in terms of stability and provides a sustaining MN topical effect as well as faster relief from fungal infection.

Physicochemical characterization, identification and improved photo-stability of alpha-lipoic acid-loaded nanostructured lipid carrier

Objective: The ultimate goal of this research is to corroborate the physicochemical characterization of nanostructured lipid carrier (NLC) loading unstable lipophilic active ingredients with an antioxidant function, such as alpha-lipoic acid (ALA), and monitoring its photochemical stability of ALA-NLC against natural daylight. NLC is an innovative active compound delivery system in pharmaceutical and cosmetic fields. It has been recommended as active substance carriers to enhance the effectiveness of lipophilic compounds.Methods: ALA-NLC was manufactured using hot high pressure homogenization technique to increase the water solubility and photo-stability. The physicochemical characterization properties of ALA-NLC have been determined in terms of nanoparticle size, zeta potential, polydispersity index value and size distribution. Size analysis was implemented through photon correlation spectroscopy and laser diffractometry. Morphological profile of nanoparticles was observed via atomic force microscopy. The loading of NLC containing ALA was evaluated by high performance liquid chromatography. ALA-NLC was subjected to UV-Vis spectrophotometer to validate the existence of ALA. Water contact angle measurement was manipulated to determine the hydrophilicity of the sample. The photo-stability of ALA-NLC within 120 days was assessed by the retention of ALA.Results: The ALA-NLC provided maximum ALA retention of 93.9% in 30 days exposure to natural daylight, the retention of free ALA only 42.5%. About 88.5% of the initial ALA in NLC system remained after 120 days under the same conditions, while the retention of free ALA only 0.7% under natural daylight irradiation. The photo-stability of ALA was considerably enhanced by NLC formulation compared with free ALA itself. Therefore, the NLC formulation provided a reliable protection of ALA against natural daylight, enhancing its photochemical stability.Conclusion: The present investigation elucidated that the NLC drastically improved the water solubility, particularly the facilitation of photo-stability of ALA exposure to natural daylight.

Improved photostability, reduced skin permeation and irritation of isotretinoin by solid lipid nanoparticles / Povećana fotostabilnost, smanjena permeacija i iritacija izotretinoina iz kruto-tekućih nanočestica

The aim of this study was to develop new solid lipid nanoparticles of isotretinoin (IT-SLNs) and evaluate the ability of IT-SLNs to improve photostability, reduce skin permeation and irritating effects. IT-SLNs were prepared by the hot high pressure homogenization method. Size, zeta potential and morphological characteristics of the preparations were assessed by transmission electron microscopy (TEM) and thermotropic properties with differential scanning calorimetry (DSC). IT-SLNs had a small average diameter of 74.05 ± 8.91 nm and high encapsulation efficiency (EE) of 80.6 ± 1.2 %. The results showed that the entrapment of IT into SLNs reduced significantly its photodegradation. The in vitro permeation data showed that IT-SLNs can accumulate in the different layers of the skin and prevent systemic uptake of IT in mouse skin. IT-SLNs also significantly increased IT accumulation in the different layers of the stratum corneum of human skin. IT-SLN formulation was significantly less irritating compared to commercial IT-GEL, which shows its potential for improving skin tolerability and being a carrier for topical delivery of IT.

Comparative Evaluation of the Effect of Permeation Enhancers, Lipid Nanoparticles and Colloidal Silica on in vivo Human Skin Penetration of Quercetin

Background/Aim: The aim of this study was to evaluate emulsions containing a penetration enhancer, lipid nanoparticles (LNs) or colloidal silica as systems to improve the topical delivery of the flavonoid quercetin. Methods: The skin penetration of quercetin was investigated in vivo on human volunteers by tape stripping. Quercetin-loaded LNs were prepared using hot high-pressure homogenization and characterized by means of dynamic light scattering and release studies. The location of the silica nanoparticles in the skin was determined by inductively coupled plasma mass spectrometry assay of silicon in the stratum corneum strips. Results and Conclusions: The penetration enhancer diethylene glycol monoethyl ether did not produce any significant increase in the fraction of the applied quercetin dose permeated in vivo into human stratum corneum (17.1 ± 3.2%) compared to the control emulsion (18.1 ± 2.3%). A greater but statistically nonsignificant accumulation of the flavonoid in the human horny layer (21.2 ± 2.9% of the applied dose) was measured following topical application of quercetin-loaded LNs (mean particle size: 527 nm). On the other hand, the addition of colloidal silica (average particle diameter: 486 nm) to the emulsion (2%, w/w) significantly increased the in vivo uptake of quercetin by the human stratum corneum to 26.7 ± 4.1% of the applied dose, the enhancing effect on permeation being more marked in the deepest horny layer strips. The measured in vivo skin penetration profile of colloidal silica showed that silica particles diffused down to the intermediate region of the human horny layer and hence could act as carrier for quercetin.

Engineering of a nanostructured lipid carrier for the poorly water-soluble drug, bicalutamide: Physicochemical investigations

The purpose of this study was to develop an optimized nanostructured lipid carrier (NLC) for bicalutamide (BCT), a poorly water-soluble drug, and to investigate its phase transition behavior during the NLC processing. BCT loaded NLCs (BCT-NLCs) were prepared using a hot high-pressure homogenization (HPH) technique. Factorial design (23) was used to identify the key formulation variables influencing particle size, percent drug encapsulation, and zeta potential of the NLC. The optimized batch (NLC-2) revealed spherical morphology with a smooth surface under scanning electron microscopy (SEM). NLC-2 achieved a high drug encapsulation of 98.48±0.70% and demonstrated good stability for six months. Drug–lipid interaction was investigated using Fourier transform infrared spectra (FT-IR) and proton nuclear magnetic resonance (1H NMR). BCT phase transition occurred during the NLC processing and BCT crystalline Form I was identified in NLC-2. The same was confirmed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Raman analysis. The in vitro release study of NLC-2, revealed peppas release kinetics with Fickian diffusion (n<0.5) as drug release mechanism. The presence of hydrophilic surfactants was significant to modulate BCT release from NLC-2. Finally, NLCs made of Precirol® ATO 5 (solid lipid) and triacetin (oil) posses the potential to entrap the poorly water-soluble drug, bicalutamide and the system can be tailor-made to meet the desired drug release. This may provide better prospects for the oral delivery of bicalutamide.

Brain delivery of camptothecin by means of solid lipid nanoparticles: Formulation design, in vitro and in vivo studies

For the purpose of brain delivery upon intravenous injection, formulations of camptothecin-loaded solid lipid nanoparticles (SLN), prepared by hot high pressure homogenisation, were designed. Incorporation of camptothecin in the hydrophobic and acidic environment of SLN matrix was chosen to stabilise the lactone ring, which is essential for its antitumour activity, and for avoiding premature loss of drug on the way to target camptothecin to the brain. A multivariate approach was used to assess the influence of the qualitative and quantitative composition on the physicochemical properties of camptothecin-loaded SLN in comparison to plain SLN. Mean particle sizes of ≤200 nm, homogenous size distributions and high encapsulation efficiencies (>90%) were achieved for the most suitable formulations. In vitro release studies in plasma, showed a prolonged release profile of camptothecin from SLN, confirming the physical stability of the particles under physiological pH. A higher affinity of the SLN to the porcine brain capillary endothelial cells (BCEC) was shown in comparison to macrophages. MTT studies in BCEC revealed a moderate decrease in the cell viability of camptothecin, when incorporated in SLN compared to free camptothecin in solution. In vivo studies in rats showed that fluorescently labelled SLN were detected in the brain after i.v. administration. This study indicates that the camptothecin-loaded SLN are a promising drug brain delivery system worth to explore further for brain tumour therapy.

Preparation and characterization of solid lipid nanoparticle-based nasal spray of budesonide.

The present research work was aimed at developing solid lipid nanoparticle (SLN)-based formulation of budesonide (BDS) for nasal delivery. Melt emulsification method was chosen for fabrication of BDS-SLN using ultrasound dispersion and hot high-pressure homogenization techniques. The Compritol888 ATO was chosen as the lipid component for SLN formulation due to highest solubility for BDS. Different surfactants were screened and it was found that combination of Tween 80 and plurol oleique has shown desired particle size with improved stability and entrapment efficiency. The optimized SLN composition had a particle size of 185.2nm with polydispersibility index of 0.387. Entrapment efficiency of the SLN composition was observed to be 61%. Further, the optimized SLN dispersion was formulated into nasal spray. In vitro permeation study was carried out using Ovis aries (Indian sheep) nasal mucosa and it was observed that the permeability of BDS nasal spray of SLN was increased significantly by 3.4-fold as compared to the plain BDS and 1.8-fold as compared to the marketed nasal formulation. Thus, SLN-based nasal drug delivery was observed to be a promising approach for improving the bioavailability of hydrophobic drugs.

Topical formulation of retinyl retinoate employing nanostructured lipid carriers

Topical formulation of retinyl retinoate (RR) was developed with nanostructured lipid carriers (NLCs), composed of Compritol or Precirol as a solid lipid, canola oil as an oil, and Tween 80 as a surfactant. Hot high pressure homogenization method was efficiently employed to yield a homogenous nanodispersion in the size range of 230–300 nm with PDI values of <0.2, regardless of lipid selection. Precirol-based NLC (P-NLC) showed higher drug entrapment than that of Compritol-based NLC (C-NLC): RR encapsulation efficiency (%) of P- and C-NLC was 97.8 and 93.8 in average, respectively; drug loading (mg RR/g lipid) was 89.6 and 83.3 in average, respectively. Processing condition at relatively low temperature of 60 °C was a key factor for maintaining RR stability. Drug release of P-NLC was greater than that of C-NLC, even though both NLCs revealed controlled release pattern. Therefore, P-NLC system was considered as a suitable vehicle for topical drug delivery, especially for heat-labile ingredient like RR.

Physicochemical Characterization, Photo-Stability and Cytotoxicity of Coenzyme Q10-Loading Nanostructured Lipid Carrier

Nanostructured lipid carrier (NLC) is prospective active ingredients delivery systems based on combinations of solid lipids and liquid oil. Aqueous dispersion of NLC was prepared via hot high pressure homogenization technique. The CoQ10-NLC aqueous dispersion was prepared in order to improve the water solubility, photo-stability of Coenzyme Q10 (CoQ10). The physicochemical characterization parameters of CoQ10-NLC have been explored regarding particle size, zeta potential, polydispersity index (PDI) value and stability of CoQ10, which is an antioxidant. HPLC was employed to monitor the loading of CoQ10 encapsulated in NLC system. Morphology profile and hydrophobicity/hydrophilicity were determined and analyzed using atomic force microscopy (AFM) and water contact angle measurements, respectively. Infrared (IR) spectrometry was exploited to confirm the possible interaction and complex formation between CoQ10 and lipids. The photo-stability of CoQ10 was powerfully improved by NLC, more than 80% of CoQ10 remained unchanged in one month under natural daylight, while the retention of free CoQ10 only 33.5% under the same conditions. CoQ10-NLC offered comparatively high protection. The retention of CoQ10 in NLC system was about 65% after five-month exposure to natural daylight, the retention of free CoQ10 only 13.3%. The CoQ10 in the NLC-based formulation showed considerably enhanced photo-stability compared with CoQ10 itself, and displayed the better protection of CoQ10. The obtained results opened new perspectives on the photo-stability of CoQ10. The MTT analysis determined CoQ10-NLC lower cytotoxicity. In conclusion, the present investigation demonstrated that the CoQ10-NLC significantly improved the water solubility, especially the enhancement of photo-stability of CoQ10 under natural daylight.

Design and In Vitro Evaluation of Solid-Lipid Nanoparticle Drug Delivery for Aceclofenac

Solid-lipid nanoparticles (SLNs) are an interesting nanoparticulate delivery system. The present work was carried out with the aim to develop a prolonged release solid-lipid nanoparticulate system for the drug using aceclofenac. Aceclofenac-loaded solid-lipid nanoparticles (ACSLNs) was prepared by hot high pressure homogenization technique. Tripalmitin was used as the lipid core. Surfactants (Poloxamer 188, Tween 80, and soya lecithin) and co-surfactant (sodium tauro glycholate) were used in the formulations. The prepared ACSLN formulations were characterized for encapsulation efficiency (EE), photon correlation spectroscopy (PCS), scanning electron microscopy (SEM), and x-ray diffraction (XRD). From these studies, mean particle diameter of the formulation prepared with combination of surfactants (Poloxmer 188 and Tween 80) was about 200 nm with spherical morphology and amorphous nature. Higher EE was obtained with SLNs prepared using combination of soya lecithin and poloxmer 188. The organization and distribution of the ingredients in the nanoparticulate system were studied by differential scanning calorimetry (DSC) and the results showed that the drug is incorporated into the solid matrix. The prepared formulations demonstrated favorable in vitro prolonged release characteristics. Experimental in vitro release data were substituted in available mathematical models to establish the release kinetics of ACSLNs and it was found to follow first-order kinetics and Higuchi diffusion mechanism. Our results suggest that these SLN formulations could constitute a promising approach for the drug delivery of aceclofenac.

Chitosan-solid lipid nanoparticles as carriers for topical delivery of tretinoin

Tretinoin (TRE) or all-trans retinoic acid is employed in the topical treatment of various skin diseases including acne and psoriasis. However, its use is strongly limited by side effects and high chemical instability. TRE encapsulation in nanostructured systems reduces these problems. Chitosan is a biopolymer that exhibits a number of interesting properties such as bioadhesion and antibacterial activity. The aim of this work was to prepare and characterize solid lipid nanoparticles (SLN) containing TRE, with and without addition of chitosan, to assess their in vitro cytotoxicity in keratinocytes and to evaluate their antibacterial activity against bacteria related to acne. SLN without (SLN-TRE) and with (SLN-chitosan-TRE) chitosan were prepared by hot high pressure homogenization. The hydrodynamic mean diameter and zeta potential were 162.7±1.4nm and −31.9±2.0mV for SLN-TRE, and 284.8±15.0nm and 55.9±3.1mV for SLN-chitosan-TRE. The SLN-chitosan-TRE exhibited high encapsulation efficiency, high physical stability in the tested period (one year), were not cytotoxic to keratinocytes and showed high antibacterial activity against P. acnes and S. aureus. Therefore chitosan-SLN can be good candidates to encapsulate TRE and to increase its therapeutic efficacy in the topical treatment of acne.

Hydrophilic coating of mitotane-loaded lipid nanoparticles: Preliminary studies for mucosal adhesion

The aim of the present work was to load mitotane, an effective drug for adrenocortical carcinoma treatment, in solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). The SLN and NLC were successfully prepared by high shear homogenization followed by hot high pressure homogenization. Formulations were composed of cetyl palmitate as the solid lipid for SLN, whereas for NLC PEGylated stearic acid was selected as solid lipid and medium chain triacylglycerols as the liquid lipid. Tween® 80 and Span® 85 were used as surfactants for all formulations. The particle size, zeta potential, polydispersity index (PI), encapsulation efficiency (EE), and loading capacity (LC) were evaluated. The SLN showed a mean particle size of 150 nm, PI of 0.20, and surface charge −10 mV, and the EE and LC could reach up to 92.26% and 0.92%, respectively. The NLC were obtained with a mean particle size of 250 nm, PI of 0.30, zeta potential −15 mV and 84.50% EE, and 0.84% LC, respectively. Hydrophilic coating of SLN with chitosan or benzalkonium chloride was effective in changing zeta potential from negative to positive values. The results suggest that mitotane was efficiently loaded in SLN and in NLC, being potential delivery systems for improving mitotane LC and controlled drug release.

In vitro cytotoxicity assays of solid lipid nanoparticles in epithelial and dermal cells

In recent years, the interest in nanostructured systems to drug delivery has increased because they offer several advantages over conventional dosage forms. Solid Lipid Nanoparticles (SLN) have been highlighted among these systems because they have advantages such as high physical stability, protection against drug degradation and ease of scale-up and manufacturing, without using organic solvent. The aim of this work was to evaluate the potential of SLN, by in vitro cytotoxicity assays, for dermal drug delivery. SLN of three different lipids were prepared by hot high pressure homogenization and the cytotoxicity was assessed by 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test in mouse 3T3 fibroblasts and human HaCaT keratinocytes. SLN showed no cytotoxic potential suggesting a great potential for dermal application.

Skin photoprotection improvement: Synergistic interaction between lipid nanoparticles and organic UV filters

A photoprotective formulation was developed with an increased sunprotection factor (SPF), compared to a conventional nanoemulsion, but having the same concentration of three molecular sunscreens, namely ethylhexyl triazone, bis-ethylhexyloxyphenol methoxyphenyl triazine, and ethylhexyl methoxycinnamate. The sunscreen mixture was incorporated into nanostructured lipid carriers (NLCs). The ability of nine different solid lipids to yield stable aqueous NLC suspensions was assessed. After the production by hot high pressure homogenization, the NLC were analyzed in terms of particle size, physical state, particle shape, ultraviolet absorbance and stability. The particle size for all NLC was around 200 nm after production. The NLC suspension with carnauba wax had superior UV absorbance, NLC from bees wax showed similar efficiency as the reference emulsion. The NLC formulations were incorporated into hydrogel formulations and the in vitro SPF was measured. This study demonstrated that approximately 45% higher SPF values could be obtained when the organic UV filters were incorporated into carnauba wax NLC, in comparison to the reference nanoemulsion and bees wax NLC. The data showed that the synergistic effect of NLC and incorporated sunscreens depends not only on the solid state of the lipid but also on its type.

Preparation, characterization and biocompatibility studies on risperidone-loaded solid lipid nanoparticles (SLN): High pressure homogenization versus ultrasound

The suitability of solid lipid nanoparticles (SLN) for the encapsulation of risperidone (RISP), an antipsychotic lipophilic drug, was assessed for oral administration. The hot high pressure homogenization (HPH) and the ultrasound (US) technique were used as production methods for SLN. All the studies on the SLN formulations were done in parallel, in order to compare the results and conclude about the advantages and limitations of both techniques. The particle sizes were in the nanometer range for all prepared SLN formulations and the zeta potential absolute values were high, predicting good long-term stability. Optical analyses demonstrated the achievement of stable colloidal dispersions. Physicochemical characterization of dispersions and bulk lipids, performed by differential scanning calorimetry (DSC) and X-ray assays, support prediction of occurrence of drug incorporation in the SLN and good long term stability of the systems. The toxicity of SLN with Caco-2 cells and the existence of contaminations derived from the production equipments were assessed by the (4,5-dimethylthiazol-2-yl)2,5-diphenyl-tetrazolium bromide (MTT) assay. The results showed 90% of cell viability after SLN exposure, with no significant differences within all prepared formulations (p > 0.05). From this study, we conclude that SLN can be considered as efficient carriers for RISP encapsulation. Moreover, HPH and US revealed to be both effective methods for SLN production.

Nanostructured Polymer and Lipid Carriers for Sunscreen. Biological Effects and Skin Permeation

The interest in developing new sunscreens is increasing due to the harmful effects of UV radiation on the skin, such as erythema, accelerated skin ageing (photoageing) and the induction of skin cancer. However, many molecular sunscreens penetrate into the skin causing photoallergies, phototoxic reactions and skin irritation. Thus, the aim of this work was the preparation and characterization of polymeric and solid lipid nanoparticles to act carriers of benzophenone-3 (BZ3), aiming to improve the safety of sunscreen products by increasing the sun protection factor (SPF), decreasing BZ3 skin penetration and decreasing BZ3 concentration in sunscreen formulation. BZ3 was encapsulated in poly(epsilon-caprolactone) (PCL) nanoparticles by the nanoprecipitation method and in solid lipid nanoparticles (SLN) by the hot high pressure homogenization method. The particles were stable for 40 days. The BZ3 encapsulated in PCL nanoparticles was released faster than BZ3 encapsulated in SLN. The sun protection factor increased when BZ3 was encapsulated in both nanostructures. However, BZ3 encapsulated in PCL nanoparticles decreased its skin permeation more than SLN-BZ3. Furthermore, BZ3 encapsulated in SLN did not exhibit cytotoxic or phototoxic effects in human keratinocytes (HaCaT cells) and BABL/c 3T3 fibroblasts, whereas PCL nanoparticles with BZ3 showed phototoxic potential in HaCaT cells. Nevertheless, BZ3 free and encapsulated in PCL nanoparticles or in SLN did not show allergic reactions in mice. Our results suggest that these nanostructures are interesting carriers for sunscreen.