Glyceryl Tristearate-Based Lipid Microparticles Loaded with the Tattoo Colorant, Acid Red 87: Colorant Retention Capacity in Excised Porcine Skin.

BACKGROUND: With the increasing diffusion of tattooing, the photolability of tattoo inks has become a critical issue, as available data indicated that several tattoo colorants are unstable under sunlight, generating potentially toxic photodegradation products. Therefore, it is desirable to enhance the photostability of coloring agents contained in tattoo inks. AIMS: Lipid microparticles (LMs) highly loaded with Acid Red 87 (C.I. 45380), a colorant used in tattoo inks, were evaluated for their effect on the colorant photoinstability. In addition, the capacity of the LMs to retain the incorporated C.I. 45380 colorant after their intradermal administration in excised porcine skin was investigated. METHODS: LMs loaded with C.I. 45380 were prepared using glyceryl tristearate as the lipidic material and phosphatidylcholine as the surfactant. Non-encapsulated C.I. 45380 or the colorant-loaded LMs were irradiated with a solar simulator for photodecomposition studies or introduced in the excised porcine skin mounted in Franz diffusion cells for stability evaluation in the dermal tissue. RESULTS AND CONCLUSION: The colorant content of the microparticles was 17.7%, and their size ranged from 25 to 170 µm. The light-induced degradation of C.I. 45380 was significantly decreased by its incorporation in the LMs from 20.2 ± 5.8% to 1.9 ± 2.1%. Moreover, after intradermal injection of free or microencapsulated C.I. 45380 in the excised pig skin, the LMs reduced by 93.7% (from 24.6 to 1.5%) the quantity of the colorant diffused and hence lost in the Franz cell receptor fluid. Hence, the LM carrier efficiently retained the entrapped C.I. 45380 following incubation in the dermal region of the isolated porcine skin, which is in favor of a long-lasting tattoo. Based on these data, the incorporation of C.I. 45380 in the LMs could represent a potentially useful strategy to reduce the photodecomposition of the tattoo colorant and its harmful interactions with the skin tissue.

In vivo Human Skin Penetration of the UV Filter Ethylhexyl Triazone: Effect of Lipid Microparticle Encapsulation.

BACKGROUND/AIMS: The data available on the skin permeability of ethylhexyl triazone (EHT), a widely used high-molecular-weight (823.1-Da) UV filter, are scarce and obtained only via in vitro studies. Therefore, we evaluated in vivo the penetration of EHT in human stratum corneum by the tape stripping technique. Moreover, the effect of EHT encapsulation in lipid microparticles (LMs) on its diffusion through the stratum corneum was examined. METHODS: LMs loaded with EHT were prepared using glyceryl behenate and phosphatidylcholine. Creams containing EHT free or encapsulated in LMs in conjunction with the two most commonly used UV filters, octyl methoxycinnamate (OMC) and butyl methoxydibenzoylmethane (BMDBM), were applied to human volunteers and the fraction of the applied sunscreen dose having penetrated into different stratum corneum layers was measured. RESULTS AND CONCLUSION: For the cream with the nonencapsulated sunscreen agent, the percentage of the applied EHT dose diffused into the stratum corneum was 21.9 ± 4.9%, not significantly different from that of the smaller-molecular-weight OMC (22.2 ± 7.6%) and BMDBM (20.5 ± 3.7%). A marked (45.7%) and statistically significant reduction in the in vivo skin penetration of EHT was attained with the cream containing microencapsulated EHT. The decreased percutaneous penetration provided by the LMs should favor the efficacy of EHT and limit potential toxicological risks.

Sweetening Inhaled Antibiotic Treatment for Eradication of Chronic Respiratory Biofilm Infection.

PURPOSE: The failure of chronic therapy with antibiotics to clear persistent respiratory infection is the key morbidity and mortality factor for patients with chronic lung diseases, primarily due to the presence of biofilm in the lungs. It is hypothesised that carbon sources, such as mannitol, could stimulate the metabolic activity of persister cells within biofilms and restore their susceptibility to antibiotics. The aims of the current study are to: (1) establish a representative in vitro model of Pseudomonas aeruginosa biofilm lung infection, and (2) investigate the effects of nebulised mannitol on antibiotic efficacy, focusing on ciprofloxacin, in the eradication of biofilm. METHOD: Air interface biofilm was cultured onto Snapwell inserts incorporated into a modified pharmacopeia deposition apparatus, the Anderson Cascade Impactor (ACI). Three different formulations including mannitol only, ciprofloxacin only and combined ciprofloxacin and mannitol were nebulised onto the P. aeruginosa biofilm using the modified ACI. Antibacterial effectiveness was evaluated using colony-forming units counts, biofilm penetration and scanning electron microscopy. RESULTS: Nebulised mannitol promotes the dispersion of bacteria from the biofilm and demonstrated a synergistic enhancement of the antibacterial efficacy of ciprofloxacin compared to delivery of antibiotic alone. CONCLUSIONS: The combination of ciprofloxacin and mannitol may provide an important new strategy to improve antibiotic therapy for the treatment of chronic lung infections. Furthermore, the development of a representative lung model of bacterial biofilm could potentially be used as a platform for future new antimicrobial pre-clinical screening.

Pulmonary delivery systems for polyphenols.

This review reports on the beneficial pharmacological properties of naturally occurring polyphenols for the treatment of inflammatory pulmonary diseases. In addition, it presents an overview of the different types of inhalable formulations which have been developed in order to achieve efficient delivery of polyphenols to the respiratory tract. The main biological activities of polyphenols (anti-oxidant and anti-inflammatory) are covered, with particular emphasis on the studies describing their therapeutic effects on different factors and conditions characteristic of lung pathologies. Special focus is on the technological aspects which influence the pulmonary delivery of drugs. The various polyphenol-based inhalable formulations reported in the literature are examined with specific attention to the preparation methodologies, aerosol performance, lung deposition and in vitro and in vivo polyphenol uptake by the pulmonary epithelial cells.

Novel nano-cellulose excipient for generating non-Newtonian droplets for targeted nasal drug delivery.

PURPOSE: Thickening polymers have been used as excipients in nasal formulations to avoid nasal run-off (nasal drip) post-administration. However, increasing the viscosity of the formulation can have a negative impact on the quality of the aerosols generated. Therefore, the study aims to investigate the use of a novel smart nano-cellulose excipient to generate suitable droplets for nasal drug delivery that simultaneously has only marginally increased viscosity while still reducing nasal drips. METHODS: Nasal sprays containing nano-cellulose at different concentrations were investigated for the additive's potential as an excipient. The formulations were characterized for their rheological and aerosol properties. This was then compared to conventional nasal spray formulation containing the single-component hydroxyl-propyl methyl cellulose (HPMC) viscosity enhancing excipient. RESULTS: The HPMC-containing nasal formulations behave in a Newtonian manner while the nano-cellulose formulations have a yield stress and shear-thinning properties. At higher excipient concentrations and shear rates, the nano-cellulose solutions have significantly lower viscosities compared to the HPMC solution, resulting in improved droplet formation when actuated through conventional nasal spray. CONCLUSIONS: Nano-cellulose materials could potentially be used as a suitable excipient for nasal drug delivery, producing consistent aerosol droplet size, and enhanced residence time within the nasal cavity with reduced run-offs compared to conventional polymer thickeners.

Resveratrol solid lipid microparticles as dry powder formulation for nasal delivery, characterization and in vitro deposition study.

This study focuses on development and in vitro characterisation of a nasal delivery system based on uncoated or chitosan-coated solid lipid microparticles (SLMs) containing resveratrol, a natural anti-inflammatory molecule, as an effective alternative to the conventional steroidal drugs. The physico-chemical characteristics of the SLMs loaded with resveratrol were evaluated in terms of morphology, size, thermal behaviour and moisture sorption. The SLMs appeared as aggregates larger than 20 µm. In vitro nasal deposition was evaluated using a USP specification Apparatus E 7-stage cascade impactor equipped with a standard or a modified nasal deposition apparatus. More than 95% of resveratrol was recovered onto the nasal deposition chamber and stage 1 of impactor, suggesting that the SLMs mostly deposited in the nasal cavity. Additionally, the SLMs were not toxic on RPMI 2650 nasal cell line up to a concentration of approximately 40 µM of resveratrol.

Brain uptake of a Zidovudine prodrug after nasal administration of solid lipid microparticles.

Our previous results demonstrated that a prodrug obtained by the conjugation of the antiretroviral drug zidovudine (AZT) with ursodeoxycholic acid (UDCA) represents a potential carrier for AZT in the central nervous system, thus possibly increasing AZT efficiency as an anti-HIV drug. Based on these results and in order to enhance AZT brain targeting, the present study focuses on solid lipid microparticles (SLMs) as a carrier system for the nasal administration of UDCA-AZT prodrug. SLMs were produced by the hot emulsion technique, using tristearin and stearic acid as lipidic carriers, whose mean diameters were 16 and 7 µm, respectively. SLMs were of spherical shape, and their prodrug loading was 0.57 ± 0.03% (w/w, tristearin based) and 1.84 ± 0.02% (w/w, stearic acid based). The tristearin SLMs were able to control the prodrug release, whereas the stearic acid SLMs induced a significant increase of the dissolution rate of the free prodrug. The free prodrug was rapidly hydrolyzed in rat liver homogenates with a half-life of 2.7 ± 0.14 min (process completed within 30 min). The tristearin SLMs markedly enhanced the stability of the prodrug (75% of the prodrug still present after 30 min), whereas the stabilization effect of the stearic acid SLMs was lower (14% of the prodrug still present after 30 min). No AZT and UDCA-AZT were detected in the rat cerebrospinal fluid (CSF) after an intravenous prodrug administration (200 µg). Conversely, the nasal administration of stearic acid based SLMs induced the uptake of the prodrug in the CSF, demonstrating the existence of a direct nose-CNS pathway. In the presence of chitosan, the CSF prodrug uptake increased six times, up to 1.5 µg/mL within 150 min after nasal administration. The loaded SLMs appear therefore as a promising nasal formulation for selective zidovudine brain uptake.

Influence of lipid microparticle encapsulation on in vitro efficacy, photostability and water resistance of the sunscreen agents, octyl methoxycinnamate and butyl methoxydibenzoylmethane.

CONTEXT: Essential requirements for the efficacy of sunscreen agents are optimal UV absorption, high photostability and resistance against water removal. OBJECTIVE: Aim of this study was to investigate the effect of encapsulation in lipid microparticles (LMs) on the overall performance of the two most commonly used sunscreen agents, octyl methoxycinnamate (OMC) and butyl methoxydibenzoylmethane (BMDBM). METHODS: LMs loaded with OMC and BMDBM were prepared by melt emulsification and characterized by optical microscopy, UV filter content and release studies. The LMs incorporating OMC and BMDBM or the nonencapsulated sunscreen agents were introduced into a model cream (oil-in-water emulsion). RESULTS: No significant differences were observed between the sun protection factor (SPF) of the formulations containing the free (SPF, 9.4 ± 1.9) or microencapsulated (SPF, 9.6 ± 1.3) UV filters. Irradiation of the creams with a solar simulator demonstrated that the photodecomposition of OMC and BMDBM was significantly decreased by encapsulation in LMs from 55.7 ± 5.3% to 46.1 ± 5.1% and 36.3 ± 3.9% to 20.1 ± 4.7%, respectively. However, in vitro water-resistance studies showed that entrapment in the LMs significantly enhanced the sunscreen agent removal caused by watering (the losses for OMC and BMDBM were 45.1 ± 6.3% and 49.2 ± 8.4%, respectively), as compared to the formulation with the nonencapsulated sunscreen agents (the losses for OMC and BMDBM were 26.7 ± 6.1% and 28.0 ± 6.7%, respectively). CONCLUSION: Incorporation in LMs can have controversial effects on UV filter efficacy. In particular, the water-resistance properties of sun-care formulations containing sunscreens loaded in LMs should be verified to assure that the photoprotective activity is maintained during usage.

Comparative evaluation of different co-antioxidants on the photochemical- and functional-stability of epigallocatechin-3-gallate in topical creams exposed to simulated sunlight.

The catechin (-)-epigallocatechin-3-gallate (EGCG) exhibits high antioxidant activity and it has been reported to provide protection of the skin against damage induced by solar UV radiation. However, EGCG is highly unstable under sunlight. The present study aimed to compare the effectiveness of the co-antioxidant agents vitamin E, butylated hydroxytoluene, vitamin C and a-lipoic acid for their potential to protect the catechin from photochemical degradation. Model creams (oil-in-water emulsions) containing EGCG (1%, w/w) alone or combined with equimolar concentrations of co-antioxidant were exposed to a solar simulator at an irradiance corresponding to natural sunlight. Photodegradation was evaluated by HPLC-UV and HPLC-ESI-MS/MS. Addition of the co-antioxidants vitamin C and a-lipoic acid to the formulation significantly reduced the light-induced decomposition of EGCG from 76.9 ± 4.6% to 20.4 ± 2.7% and 12.6 ± 1.6%, respectively. Conversely, butylated hydroxytoluene had no effect (EGCG loss, 78.1 ± 4.6%) and vitamin E enhanced the EGCG photolysis to 84.5 ± 3.4%. The functional stability of the catechin in the creams exposed to the solar simulator was also evaluated by measuring the in vitro antioxidant activity. Following irradiation, the reduction of the EGCG formulation antioxidant power was lower (21.8%) than the extent of degradation (76.9%), suggesting the formation of photoproducts with antioxidant properties. The influence of the examined co-antioxidants on the functional stability of the catechin under simulated sunlight paralleled that measured for the EGCG photodecomposition, a-lipoic acid exerting the greatest stabilising effect (antioxidant activity decrease, 1.4%). These results demonstrated that a-lipoic acid is an effective co-antioxidant agent for the stabilization of EGCG in dermatological products for skin photoprotection.

Comparison of spray congealing and melt emulsification methods for the incorporation of the water-soluble salbutamol sulphate in lipid microparticles.

CONTEXT: Salbutamol sulphate is widely used as bronchodilator for the treatment of asthma. Its use is limited by the relatively short duration of action and hence sustained delivery of salbutamol sulphate offers potential benefits to patients. OBJECTIVE: This study explores the preparation of lipid microparticles (LMs) as biocompatible carrier for the prolonged release of salbutamol sulphate. MATERIALS AND METHODS: The LMs were produced using different lipidic materials and surfactants, by classical melt emulsification-based methods (oil-in-water and water-in-oil-in-water emulsions) and the spray congealing technique. RESULTS: For the LMs obtained by melt emulsification a lack of release modulation was observed. On the other hand, the sustained release of salbutamol sulphate was achieved with glyceryl behenate microparticles prepared by spray congealing. These LMs were characterized by scanning electron microscopy, X-ray diffractometry and differential scanning calorimetry. The drug loading was 4.72% (w/w). The particle size distribution measured by laser diffraction and electrical zone sensing was represented by a volume median diameter (Dv(50)) of 51.7-71.4 µm. Increasing the atomization air pressure from 4 to 8 bar produced a decrease of the Dv(50) to 12.7-17.5 µm. CONCLUSIONS: Incorporation of the hydrophilic salbutamol sulphate into LMs with sustained release characteristics was achieved by spray congealing.

Modelling acute myeloid leukemia (AML): What's new? A transition from the classical to the modern.

Acute myeloid leukemia (AML) is a heterogeneous malignancy affecting myeloid cells in the bone marrow (BM) but can spread giving rise to impaired hematopoiesis. AML incidence increases with age and is associated with poor prognostic outcomes. There has been a disconnect between the success of novel drug compounds observed in preclinical studies of hematological malignancy and less than exceptional therapeutic responses in clinical trials. This review aims to provide a state-of-the-art overview on the different preclinical models of AML available to expand insights into disease pathology and as preclinical screening tools. Deciphering the complex physiological and pathological processes and developing predictive preclinical models are key to understanding disease progression and fundamental in the development and testing of new effective drug treatments. Standard scaffold-free suspension models fail to recapitulate the complex environment where AML occurs. To this end, we review advances in scaffold/matrix-based 3D models and outline the most recent advances in on-chip technology. We also provide an overview of clinically relevant animal models and review the expanding use of patient-derived samples, which offer the prospect to create more "patient specific" screening tools either in the guise of 3D matrix models, microphysiological "organ-on-chip" tools or xenograft models and discuss representative examples.

Magnetised thermo responsive lipid vehicles for targeted and controlled lung drug delivery.

PURPOSE: Conditions such as lung cancer currently lack non-invasively targetable and controlled release topical inhalational therapies. Superparamagnetic iron-oxide nanoparticles (SPIONs) have shown promising results as a targetable therapy. We aimed to fabricate and test the in-vitro performance of particles with SPION and drug within a lipid matrix as a potentially targetable and thermo-sensitive inhalable drug-delivery system. METHODS: Budesonide and SPIONs were incorporated into lipid particles using oil-in-water emulsification. Particles size, chemical composition, responsiveness to magnetic field, thermosensitiveness and inhalation performance in-vitro were investigated. RESULTS: Particles of average diameter 2-4 µm with budesonide and SPIONs inside the lipid matrix responded to a magnetic field with 100% extraction at a distance of 5 mm. Formulations were shown to have accelerated rate of drug release at hyperthermic temperatures (45°C)--controlled release. The produced inhalation dry powder presented promising inhalation performance, with an inhalable fine particle fraction of 30%. CONCLUSIONS: The lipid system presented thermo-sensitive characteristics, suitable for controlled delivery, the model drug and SPION loaded lipid system was magnetically active and movable using simple permanent magnets, and the system demonstrates promise as an effective drug vehicle in targeted and controlled inhalation therapy.

Preparation and in vitro evaluation of salbutamol-loaded lipid microparticles for sustained release pulmonary therapy.

The aim of this study was to prepare lipid microparticles (LMs) loaded with the polar bronchodilator agent salbutamol, and designed for sustained release pulmonary delivery. The microparticles were produced by melt emulsification followed by a sonication step, using different biocompatible lipid carriers (tristearin, stearic acid and glyceryl behenate) and phosphatidylcholine as the surfactant. The use of salbutamol free base, rather than salbutamol sulphate, was necessary to obtain the incorporation of the drug in the lipid particle matrix. The prolonged release of salbutamol base was achieved only by the glyceryl behenate microparticles (40.9% of encapsulated drug being released after 8 h). The salbutamol loading was 4.2% ± 0.1 and the mass median diameter, determined by laser diffraction, ranged from 4.8 to 5.4 µm. The sustained release of LMs were formulated as a carrier-free dry powder for inhalation and exhibited a fine particle fraction of 17.3% ± 2.2, as measured by multi-stage liquid impinger.

Development and in vitro characterization of a novel pMDI diclofenac formulation as an inhalable anti-inflammatory therapy for cystic fibrosis.

Anti-inflammatory treatment options for cystic fibrosis (CF) patients are currently limited and as such, there is an imperative need to develop new anti-inflammatory agents to reduce the persistent inflammation present within CF lungs. This study explored the potential of Diclofenac (DICLO) as a novel inhaled anti-inflammatory drug for CF treatment. The anti-inflammatory activity of DICLO on an air-liquid interface (ALI) cell culture model of healthy (NuLi-1) and CF (CuFi-1) airways showed a significant reduction in the secretion of pro-inflammatory cytokines, IL-6 and IL-8. Therefore, pressurized metered dose inhaler (pMDI) DICLO formulations were developed to allow targeted DICLO delivery to CF airways. As such, two pMDI DICLO formulations with varying ethanol concentrations: 5% (w/w) equating to 150 µg of DICLO per dose (Low dose), and 15% (w/w) equating to 430 µg of DICLO per dose (High dose) were developed and characterized to determine the optimum formulation. The Low dose pMDI DICLO formulation showed a significantly smaller particle diameter with uniform distribution resulting in a greater aerosol performance when compared to High dose formulation. Consequently, the Low dose pMDI DICLO formulation was further evaluated in terms of in vitro transport characteristics and anti-inflammatory activity. Importantly, the DICLO pMDI displayed anti-inflammatory activity in both healthy and CF in vitro models, highlighting the potential of an aerosolized low-dose DICLO formulation as a promising inhaled anti-inflammatory therapy for CF treatment.

Incorporation in Lipid Microparticles of Acid Red 87, a Colorant Used in Tattoo Inks: Effect on Photodegradation Under Simulated Sunlight and Laser Radiation.

Tattoo colorants decompose under solar radiation and when exposed to laser light for their removal, leading to the accumulation in the dermis of toxic products. Aim of this study was to develop lipid microparticles (LMs) loaded with the colorant, Acid Red 87 (C.I. 45380) used in tattoo inks, and to investigate the effect of this system on the photostability of the colorant under simulated sunlight or laser irradiation. LMs loaded with C.I. 45380 were prepared by melt emulsification using tristearin and phosphatidylcholine as excipients. They were characterized by optical microscopy, laser diffraction, X-ray diffraction and release studies. Free C.I. 45380 and the colorant-loaded LMs were irradiated with a solar simulator or a Q-switched laser. Irradiation with a solar simulator demonstrated that photodecomposition of C.I. 45380 was markedly reduced by incorporation of the dye in the LMs, from 20.5 ± 4.6% to 1.3 ± 1.8%. Conversely, the laser-induced degradation of the colorant (30.1 ± 6.6%) was not significantly influenced by encapsulation in the LMs (the encapsulated C.I. 45380 loss was 27.4 ± 5.5%). Incorporation of C.I. 45380 in lipid microparticles enhances the photostability under sunlight of tattoo inks containing this colorant, without affecting its laser-induced degradation and hence laser removal efficiency.

Incorporation of quercetin in lipid microparticles: effect on photo- and chemical-stability.

Lipid microparticles loaded with the flavonoid, quercetin were developed in order to enhance its stability in topical formulations. The microparticles were produced using tristearin as the lipid material and phosphatidylcholine as the emulsifier. The obtained lipoparticles were characterized by release studies, scanning electron microscopy and powder X-ray diffractometry. The quercetin loading was 12.1% (w/w). Free or microencapsulated quercetin was introduced in a model cream formulation (oil-in-water emulsion) and irradiated with a solar simulator. The extent of photodegradation was measured by high-performance liquid chromatography. The light-induced decomposition of quercetin in the cream vehicle was markedly decreased by incorporation into the lipid microparticles (the extent of degradation was 23.1+/-3.6% for non-encapsulated quercetin compared to 11.9+/-2.5% for the quercetin-loaded microparticles) and this photostabilization effect was maintained over time. Moreover, the chemical instability of quercetin, during 3-month storage of the formulations at room temperature and in the dark, was almost completely suppressed by the lipid microparticle system. Therefore incorporation of quercetin in lipoparticles represents an effective strategy to enhance its stability in dermatological products.

Co-loading of a photostabilizer with the sunscreen agent, butyl methoxydibenzoylmethane in solid lipid microparticles.

The sunscreen agent, butyl methoxydibenzoylmethane (BMDBM), one of the most widely used UV-A filter, undergoes decomposition under sunlight exposure, which is a limiting factor on its overall performance. To reduce the sunscreen photodegradation, this study investigates the incorporation into solid lipid microparticles (SLMs) of BMDBM together with the photostabilizer, 4-methylbenzylidene camphor (MBC). The microparticles were produced by the melt dispersion technique using various lipid materials (tristearin, glyceryl behenate, and stearic acid) and hydrogenated phosphatidylcholine as the surfactant. The highest retention capacity for BMDBM and MBC was achieved with tristearin microparticles. These SLMs were characterized by scanning electron microscopy and powder X-ray diffraction analyses. The BMDBM and MBC loading was 10.4 and 10.1%, respectively. The efficacy of the SLMs was evaluated after their introduction in a conventional cream (oil-in-water emulsion). The light-induced decomposition of BMDBM was decreased by encapsulation into the SLMs (the extent of degradation was 33.8 +/- 5.5% for unencapsulated BMDBM/MBC and 25.3 +/- 4.2% for BMDBM-loaded microparticles in conjunction with free MBC). Moreover, the co-loading of the MBC stabilizer in the SLMs produced a further reduction of the photodegradation of the UV-A filter (the BMDBM loss was 16.9 +/- 5.9%) compared with the microparticles containing BMDBM without MBC. Therefore, incorporation in lipid microparticles of BMDBM together with the MBC photostabilizer is more effective in enhancing the UV-A filter photostability than the SLMs loaded with BMDBM alone.

Incorporation in lipid microparticles of the UVA filter, butyl methoxydibenzoylmethane combined with the UVB filter, octocrylene: effect on photostability.

The aim of this study was to reduce the photoinstability of butyl methoxydibenzoylmethane (BMDBM), the most widely used UVA filter, by incorporating it in lipid microparticles (LMs) alone or together with the UVB filter octocrylene (OCR), acting also as photostabilizer. Microparticles loaded with BMDBM or with combined BMDBM and OCR were produced by the hot emulsion technique, using glyceryl behenate as lipid material and poloxamer 188 as surfactant. The LMs were characterized by release studies, scanning electron microscopy, and powder X-ray diffractometry. The BMDBM and OCR loading was 15.2% and 10.6%, respectively. In order to reproduce the conditions prevalent in commercial sunscreen products, the photoprotective efficacy of the LMs was evaluated after their introduction in a model cream (oil-in-water emulsion) containing a mixture of UVA and UVB filters. A small but statistically significant decrease in BMDBM photodegradation was obtained when the UVA filter was encapsulated alone into the LMs (the extent of degradation was 28.6% +/-2.4 for non-encapsulated BMDBM and 26.0% +/-2.5 for BMDBM-loaded microparticles). On the other hand, the co-loading of OCR in the LMs produced a more marked reduction in the light-induced decomposition of microencapsulated BMDBM (the UVA filter loss was 21.5% +/-2.2). Therefore, incorporation in lipid microparticles of BMDBM together with the sunscreen OCR is more effective in enhancing the UVA filter photostability than LMs loaded with BMDBM alone.

Simvastatin Nanoparticles Reduce Inflammation in LPS-Stimulated Alveolar Macrophages.

Simvastatin (SV) is widely used as a lipid-lowering medication that has also been found to have beneficial immunomodulatory effects for treatment of chronic lung diseases. Although its anti-inflammatory activity has been investigated, its underlying mechanisms have not yet been clearly elucidated. In this study, the anti-inflammatory and antioxidant effects and mechanism of simvastatin nanoparticles (SV-NPs) on lipopolysaccharide-stimulated alveolar macrophages (AMs) NR8383 cells were investigated. Quantitative cellular uptake of SV-NPs, the production of inflammatory mediators (interleukin-6, tumor necrosis factor, and monocyte chemoattractant protein-1), and oxidative stress (nitric oxide) were tested. Furthermore, the involvement of the nuclear factor κB (NF-κB) signaling pathway in activation of inflammation in AMs and the efficacy of SV were visualized using immunofluorescence. Results indicated that SV-NPs exhibit a potent inhibitory effect on nitric oxide production and secretion of inflammatory cytokine in inflamed AM, without affecting cell viability. The enhanced anti-inflammatory activity of SV-NPs is likely due to SV-improved chemical-physical stability and higher cellular uptake into AM. The study also indicates that SV targets the inflammatory and oxidative response of AM, through inactivation of the NF-κB signaling pathway, supporting the pharmacological basis of SV for treatment of chronic inflammatory lung diseases.