Curcumin and quercetin co-encapsulated in nanoemulsions for nasal administration: A promising therapeutic and prophylactic treatment for viral respiratory infections.

One of the most frequent causes of respiratory infections are viruses. Viruses reaching the airways can be absorbed by the human body through the respiratory mucosa and mainly infect lung cells. Several viral infections are not yet curable, such as coronavirus-2 (SARS-CoV-2). Furthermore, the side effect of synthetic antiviral drugs and reduced efficacy against resistant variants have reinforced the search for alternative and effective treatment options, such as plant-derived antiviral molecules. Curcumin (CUR) and quercetin (QUE) are two natural compounds that have been widely studied for their health benefits, such as antiviral and anti-inflammatory activity. However, poor oral bioavailability limits the clinical applications of these natural compounds. In this work, nanoemulsions (NE) co-encapsulating CUR and QUE designed for nasal administration were developed as promising prophylactic and therapeutic treatments for viral respiratory infections. The NEs were prepared by high-pressure homogenization combined with the phase inversion temperature technique and evaluated for their physical and chemical characteristics. In vitro assays were performed to evaluate the nanoemulsion retention into the porcine nasal mucosa. In addition, the CUR and QUE-loaded NE antiviral activity was tested against a murine ß-COV, namely MHV-3. The results evidenced that CUR and QUE loaded NE had a particle size of 400 nm and retention in the porcine nasal mucosa. The antiviral activity of the NEs showed a percentage of inhibition of around 99 %, indicating that the developed NEs has interesting properties as a therapeutic and prophylactic treatment against viral respiratory infections.

Fluconazole and propolis co-encapsulated in chitosan nanoparticles for the treatment of vulvovaginal candidiasis in a murine model.

Vulvovaginal candidiasis (VVC) is a fungal infection caused mainly by Candida albicans. The treatment of VVC with azoles has been impaired due to the increased cases of resistance presented by this pathogen. The aim of the present study was to investigate the antifungal activity of mucoadhesive chitosan nanoparticles encapsulating both green propolis and fluconazole for topical use in the treatment of VVC. The nanoparticles were prepared by the ionic gelation method, resulting in a size of 316.5 nm containing 22 mg/kg of green propolis and 2.4 mg/kg of fluconazole. The nanoparticles were non-toxic in vitro using red blood cells or in vivo in a Galleria mellonella toxicity model. The treatment of female BALB/c mice infected by C. albicans ATCC 10231 with topical nanoparticles co-encapsulating fluconazole and green propolis was effective even using a fluconazole amount 20 times lower than the amount of miconazole nitrate 2% cream. Considering that the mucoadhesive property of chitosan, which is known to allow a prolonged retention time of the compounds at the mucous epithelia, the antifungal potential of the phenols and flavonoids present in green propolis may have favored the effectiveness of this treatment. These results indicate that this formulation of topical use for fluconazole associated with green propolis can be used as a promising approach to therapy for the treatment of VVC, thus contributing to reducing the development of resistance to azoles.

Vulvovaginal candidiasis is a fungal infection for which we search for alternatives for its treatment. Thus, a nanoparticle formulation based on fluconazole and green propolis was developed. These nanoparticles were tested, and we obtained adequate results in laboratory tests.

Pharmacokinetics and Anti-Tumor Efficacy of PEGylated Liposomes Co-Loaded with Cisplatin and Mifepristone.

Although cisplatin is an effective chemotherapy drug used against many types of cancer, it has poor bioavailability, produces severe adverse effects, and frequently leads to tumor resistance. Consequently, more effective formulations are needed. The co-administration of cisplatin with mifepristone, which counters an efflux pump drug-resistance mechanism in tumor cells, has shown important synergism, but without resolving the problem of poor bioavailability. Specificity to tumor tissue and bioavailability have been improved by co-encapsulating cisplatin and mifepristone in a liposomal formulation (L-Cis/MF), which needs further research to complete pre-clinical requirements. The aim of this current contribution was to conduct a pharmacokinetic study of cisplatin and mifepristone in male Wistar rats after administration of L-Cis/MF and the conventional (unencapsulated) formulation. Additionally, the capacity of L-Cis/MF to reduce tumor growth in male nude mice was evaluated following the implantation of xenografts of non-small-cell lung cancer. The better pharmacokinetics (higher plasma concentration) of cisplatin and mifepristone when injected in the liposomal versus the conventional formulation correlated with greater efficacy in controlling tumor growth. Future research on L-Cis/MF will characterize its molecular mechanisms and apply it to other types of cancer affected by the synergism of cisplatin and mifepristone.

Co-encapsulation of Paprika and Cinnamon Oleoresins by Spray Drying in a Mayonnaise Model: Bioaccessibility of Carotenoids Using in vitro Digestion.

This study aimed to investigate the digestibility and bioaccessibility of spray-dried microparticles co-encapsulating paprika and cinnamon oleoresins using simulated gastrointestinal conditions. It focused on exploring the potential of these co-encapsulated active compounds, which possess diverse technological and functional properties, particularly within a food matrix, in order to enhance their bioavailability. Mayonnaise was selected as the food matrix for its ability to promote the diffusion of carotenoids, as most hydrophobic compounds are better absorbed in the intestine when accompanied by digestible lipids. Model spice mayonnaise, containing 0.5 wt% paprika and cinnamon microparticles content, was formulated in compliance with Brazilian regulations for spices, seasonings, and sauce formulations. Droplet size distribution, optical microscopy and fluorescence microscopy analyses were conducted on the microparticles, model spice mayonnaise, and standard mayonnaise both before and after in vitro gastric and intestinal digestion. Following digestion, all samples demonstrated droplet aggregation and coalescence. Remarkably, dispersed particles (37.40 ± 2.58%) and model spice mayonnaise (17.76 ± 0.07%) showed the highest release rate of free fatty acids (FFAs), indicating efficient lipid digestion. The study found that using mayonnaise as a delivery system significantly increased bioaccessibility (22.7%). This suggests that particles in an aqueous medium have low solubility, while the high lipid composition of mayonnaise facilitates the delivery of active compounds from carotenoids present in paprika and cinnamon oleoresin after digestion.

Co-Encapsulation of Drugs for Topical Application-A Review.

Achieving the best possible outcome for the therapy is the main goal of a medicine. Therefore, nanocarriers and co-delivery strategies were invented to meet this need, as they can benefit many diseases. This approach was applied specifically for cancer treatment, with some success. However, these strategies may benefit many other clinical issues. Skin is the largest and most exposed organ of the human body, with physiological and psychological properties. Due to its exposition and importance, it is not difficult to understand how many skin diseases may impact on patients' lives, representing an important burden for society. Thus, this review aims to summarize the state of the art in research concerning nanocarriers and co-delivery strategies for topical agents' applications targeting skin diseases. The challenge for the medicine of the future is to deliver the drug with spatial and temporal control. Therefore, the co-encapsulation of drugs and the appropriate form of administration for them are so important and remain as unmet needs.

Use of red onion (Allium cepa L.) residue extract in the co-microencapsulation of probiotics added to a vegan product.

This study aimed to develop a functional strawberry pulp containing the combination of Lactobacillus casei and bioactive compounds from red onion peel extract into the microparticles formulations to improve bacteria survival during storage and product consumption. To achieve this goal, the addition of different concentrations of red onion peel extract added to the microparticles was evaluated: 5, 20 and 40 %. Microparticles were morphologically characterized and the encapsulation efficiency of the bioactive compounds were evaluated. The physicochemical and microbiological characteristics of the fruit pulp were within the required standards, regardless of the formulation evaluated. As for the pulp added from the microparticles, their physicochemical and microbiological features and probiotic survival under simulated gastrointestinal conditions and storage were analyzed; the size of the microparticles ranged from 136.00 to 305.00 µm. The encapsulation efficiency of both, probiotics and compounds was satisfactory over the different treatments. Indeed, the results pointed out values in the range from 77.77 to 92.11 % for probiotic bacteria; from28.88 to 50.18 % for reducing compounds; 35.72 to 69.01 % for flavonoids; and 25.39 to 60.00 % for total monomeric anthocyanins. The formulations of alginate microparticles and alginate +5 % extract had the best results of L. casei probiotic viability in strawberry pulp under simulated gastrointestinal conditions and during storage at -18 °C for 60 days. In conclusion, red onion peel extract at low concentrations can help the survival of the probiotic L. casei under different conditions.

Long-Circulating and Fusogenic Liposomes Loaded with Paclitaxel and Doxorubicin: Effect of Excipient, Freezing, and Freeze-Drying on Quality Attributes.

Liposomes can increase plasma half-life, enhance targeting, and diminish the side-effects of loaded drugs. On the downside, physical and chemical instabilities of dispersions often result in a reduced lifespan, which limits their availability on the market. Solid formulations obtained by freeze-drying can immobilize vesicles and provide extended shelf life. For both processes, the choice of excipients and process parameters are crucial to protect the carrier layers against tension caused by freezing and/or dehydration. The aim of this work is to evaluate the influence of freezing and drying parameters, besides excipient choice, to obtain solid long-circulating and fusogenic liposomes (LCFL-PTX/DXR) co-encapsulating paclitaxel (PTX) and doxorubicin (DXR) at a synergistic ratio (1:10). METHODS: LCFL-PTX/DXR was evaluated by freeze-drying microscopy (glass transition, Tg'), differential scanning calorimetry (collapse temperature, Tc), freeze-thawing and freeze-drying processes. Freeze-dried samples were evaluated by thermogravimetry (residual moisture) and the resuspended liposomes were characterized in terms of size, polydispersity index (PI), zeta potential (ZP), and drug content. Liposomes morphology was evaluated by cryomicroscopy. RESULTS: Trehalose protected PTX cargo upon freeze-thawing and more than 80% of the original DXR retention. The formulations with trehalose resulted in a cake with 5-7% of moisture content (200-240 nm); 44-60% of PTX retention, and 25-35% of DXR retention, with the variations caused by cryoprotector concentration and process changes. CONCLUSIONS: Trehalose protected liposome integrity, maintaining PTX retention and most of DXR upon freeze-thawing. Freeze-drying reduced the retention of both drugs inside all liposomes, whereas formulation with trehalose presented minor losses. Therefore, this frozen formulation is an alternative product option, with no need for manipulation before use.

Microencapsulation and co-encapsulation of bioactive compounds for application in food: challenges and perspectives / Microencapsulação e co-encapsulação de compostos bioativos para aplicação em alimentos: desafios e perspectivas

ABSTRACT: The availability of different food products containing bioactive compounds promotes their inclusion in the daily diet of consumers. However, the effective and safe delivery of such products requires certain precautions to ensure their preservation, stability, and bioavailability when consumed. Microencapsulation is a great alternative, which is a method capable of protecting different bioactive compounds, including probiotic cells, prebiotic compounds, and some antioxidant substances such as phenolic compounds, anthocyanins, flavonoids, and vitamins. Therefore, this study aimed to perform a literature review and present different alternatives to make bioactive compounds viable through microencapsulation, increase their stability and viability when applied in different food matrices, and address the existing challenges regarding their effectiveness.

RESUMO: A oferta de diferentes produtos alimentícios que contenham compostos bioativos facilita a sua inserção na dieta como parte do dia a dia do consumidor. No entanto, para que estes compostos sejam entregues de forma segura e eficaz, o uso de certos meios se torna necessário para garantir sua preservação, estabilidade e biodisponibilidade quando consumidos. Com esta finalidade, apresenta-se como uma grande alterativa a microencapsulação, que é um método capaz de fornecer proteção a diferentes compostos bioativos, que incluem células probióticas, compostos prebióticos, e algumas substâncias antioxidantes como compostos fenólicos, antocianinas, flavonoides, vitaminas, dentre outros e garantir uma melhor efetividade na sua entrega. O objetivo deste trabalho foi realizar uma revisão apresentando formas de viabilizar os compostos bioativos através da microencapsulação, para aumentar sua estabilidade e viabilidade diante da aplicação em diferentes matrizes alimentícias, além de abordar os desafios existentes para a sua efetividade.

Microencapsulation and co-encapsulation of bioactive compounds for application in food: challenges and perspectives / Microencapsulação e co-encapsulação de compostos bioativos para aplicação em alimentos: desafios e perspectivas

The availability of different food products containing bioactive compounds promotes their inclusion in the daily diet of consumers. However, the effective and safe delivery of such products requires certain precautions to ensure their preservation, stability, and bioavailability when consumed. Microencapsulation is a great alternative, which is a method capable of protecting different bioactive compounds, including probiotic cells, prebiotic compounds, and some antioxidant substances such as phenolic compounds, anthocyanins, flavonoids, and vitamins. Therefore, this study aimed to perform a literature review and present different alternatives to make bioactive compounds viable through microencapsulation, increase their stability and viability when applied in different food matrices, and address the existing challenges regarding their effectiveness.(AU)

A oferta de diferentes produtos alimentícios que contenham compostos bioativos facilita a sua inserção na dieta como parte do dia a dia do consumidor. No entanto, para que estes compostos sejam entregues de forma segura e eficaz, o uso de certos meios se torna necessário para garantir sua preservação, estabilidade e biodisponibilidade quando consumidos. Com esta finalidade, apresenta-se como uma grande alterativa a microencapsulação, que é um método capaz de fornecer proteção a diferentes compostos bioativos, que incluem células probióticas, compostos prebióticos, e algumas substâncias antioxidantes como compostos fenólicos, antocianinas, flavonoides, vitaminas, dentre outros e garantir uma melhor efetividade na sua entrega. O objetivo deste trabalho foi realizar uma revisão apresentando formas de viabilizar os compostos bioativos através da microencapsulação, para aumentar sua estabilidade e viabilidade diante da aplicação em diferentes matrizes alimentícias, além de abordar os desafios existentes para a sua efetividade.(AU)

Combined paclitaxel-doxorubicin liposomal results in positive prognosis with infiltrating lymphocytes in lung metastasis.

Aim: To investigate the effect of liposomes containing the classical cytotoxic drugs paclitaxel and doxorubicin (Lipo-Pacli/Dox), against a metastatic breast cancer model. We also investigated if Lipo-Pacli/Dox was capable of reverting the tolerogenic environment of metastatic lesions. Materials & methods: Immunogenic cell death induction by the Pacli/Dox combination was assessed in vitro. Antitumor activity and in vivo safety of Lipo-Pacli/Dox were evaluated using a 4T1 breast cancer mouse model Results: Lipo-Pacli/Dox, with a size of 189 nm and zeta potential of -5.01 mV, promoted immune system activation and partially controlled the progression of pulmonary metastasis. Conclusion: Lipo-Pacli/Dox was useful to control both primary tumor and lung metastasis in breast cancer (4T1) mice model. Additionally, Lipo-Pacli/Dox acts as an immunological modulator for this metastatic breast cancer model.

Liposomes Co-Encapsulating Cisplatin/Mifepristone Improve the Effect on Cervical Cancer: In Vitro and In Vivo Assessment.

Cervical cancer is usually diagnosed in the later stages despite many campaigns for early detection and continues to be a major public health problem. The standard treatment is cisplatin-based chemotherapy plus radiotherapy, but patient response is far from ideal. In the research for new drugs that enhance the activity of cisplatin, different therapeutic agents have been tested, among them the antiprogestin mifepristone. Nevertheless, the efficacy of cisplatin is limited by its low specificity for tumor tissue, which causes severe side effects. Additionally, cervical tumors often become drug resistant. These problems could possibly be addressed by the use of liposome nanoparticles to encapsulate drugs and deliver them to the target. The aim of this study was to prepare liposome nanoparticles that co-encapsulate cisplatin and mifepristone, evaluate their cytotoxicity against HeLa cells and in vivo with subcutaneous inoculations of xenografts in nu/nu mice, and examine some plausible mechanisms of action. The liposomes were elaborated by the reverse-phase method and characterized by physicochemical tests. The nanoparticles had a mean particle size of 109 ± 5.4 nm and a Zeta potential of -38.7 ± 1.2 mV, the latter parameter indicating a stable formulation. These drug-loaded liposomes significantly decreased cell viability in vitro and tumor size in vivo, without generating systemic toxicity in the animals. There was evidence of cell cycle arrest and increased apoptosis. The promising results with the co-encapsulation of cisplatin/mifepristone warrant further research.

Development of Long-Circulating and Fusogenic Liposomes Co-encapsulating Paclitaxel and Doxorubicin in Synergistic Ratio for the Treatment of Breast Cancer.

BACKGROUND: The co-encapsulation of paclitaxel (PTX) and doxorubicin (DXR) in liposomes has the potential to offer pharmacokinetic and pharmacodynamic advantages, providing delivery of both drugs to the tumor at the ratio required for synergism. OBJECTIVE: To prepare and characterize long-circulating and fusogenic liposomes co-encapsulating PTX and DXR in the 1:10 molar ratio (LCFL-PTX/DXR). METHODS: LCFL-PTX/DXR was prepared by the lipid film formation method. The release of PTX and DXR from liposomes was performed using a dialysis method. Studies of cytotoxicity, synergism, and cellular uptake were also carried out. RESULTS: The encapsulation percentage of PTX and DXR was 74.1 ± 1.8 % and 89.6 ± 12.3%, respectively, and the mean diameter of the liposomes was 244.4 ± 28.1 nm. The vesicles remained stable for 30 days after their preparation. The drugs were simultaneously released from vesicles during 36 hours, maintaining the drugs combination in the previously established ratio. Cytotoxicity studies using 4T1 breast cancer cells showed lower inhibitory concentration 50% (IC50) value for LCFL-PTX/DXR treatment (0.27 ± 0.11 µm) compared to the values of free drugs treatment. In addition, the combination index (CI) assessed for treatment with LCFL-PTX/DXR was equal to 0.11 ± 0.04, showing strong synergism between the drugs. Cell uptake studies have confirmed that the molar ratio between PTX and DXR is maintained when the drugs are administered in liposomes. CONCLUSION: It was possible to obtain LCFL-PTX/DXR suitable for intravenous administration, capable of releasing the drugs in a fixed synergistic molar ratio in the tumor region.

Sclareol is a potent enhancer of doxorubicin: Evaluation of the free combination and co-loaded nanostructured lipid carriers against breast cancer.

AIMS: In this work, it was sought to determine if there was synergism between doxorubicin (DOX), a well-known antineoplastic, and sclareol (SC), a diterpene from natural origin, in breast cancer treatment. Moreover, it was investigated if their co-loading in the same nanocarrier would result in a gain of activity and/or a toxicity diminishment. MAIN METHODS: The synergism of the DOX:SC combination was evaluated in MDA-MB-231 and 4T1 cells. A nanostructured lipid carrier (NLC) co-encapsulating DOX and SC in their synergistic molar ratio was prepared and characterised, in terms of mean diameter, zeta potential, DOX encapsulation efficiency, small angle X-ray scattering, differential scanning calorimetry, and polarised light microscopy for further intravenous administration. The anticancer activity of the combination, free and encapsulated, was evaluated in 4T1-tumour bearing mice. KEY FINDINGS: It was determined that DOX:SC combination at the molar ratio 1:1.9 presents better synergistic anticancer activity than the molar ratio 1:7.5 in vitro. DOX:SC-loaded NLC (NLC-DOX-SC) improved in vitro cytotoxic and in vivo antitumour activity compared to free DOX. Although NLC-DOX-SC and free DOX:SC, at the synergistic molar ratio, showed similar activity in the in vivo study, the free combination provoked body weight loss, behaviour alterations and haematological toxicity in the animals, while this was not observed for NLC-DOX-SC. SIGNIFICANCE: This work shows that SC and DOX present synergistic anticancer activity for breast cancer treatment whereas NLC-DOX-SC was a feasible alternative to attain the benefits posed by DOX:SC combination but with none to fewer side effects.

Liposomes Co- encapsulating Anticancer Drugs in Synergistic Ratios as an Approach to Promote Increased Efficacy and Greater Safety.

The era of chemotherapy began in the 1940s, but it was in the 1960s that it was seen as really promising when the first patients with childhood acute lymphoblastic leukemia were cured with combination chemotherapy. Today, it is known that due to resistance to single agents, combination therapy is essential for tumor eradication and cure. In the last decade, studies have shown that anticancer drug combinations can act synergistically or antagonistically against tumor cells in vitro, depending on the ratios of the individual drugs forming the combination. From this observation and facing the possibility of maintaining the in vivo synergistic ratio of combinations came the idea of co-encapsulating anticancer agents in nanosystems. In vivo studies validated this idea by showing that the co-encapsulation of anticancer agents in liposomes allows the maintenance of drug ratios in the plasma and the delivery of fixed drug ratios directly to tumor tissue, leading to a better efficacy compared to the administration of the free drugs combination. Liposomes co-encapsulating irinotecan/floxuridine are now in Phase II trial, and liposomes co-encapsulating cytarabine/daunorubicin were recently approved by the FDA for treatment of patients with acute myeloid leukemia.

Development and validation of a RP-HPLC method for the simultaneous detection and quantification of simvastatin's isoforms and coenzyme Q10 in lecithin/chitosan nanoparticles.

Hybrid nanocapsules constituted of phospholipids and polysaccharides have been proposed as colloidal systems for the delivery of drugs via non-parenteral administration routes, due their capacity of high drug loading, controlled drug release and targeted delivery to the specific organ. Moreover, nanoparticles systems offer the possibility of co-encapsulation of drugs in the same drug delivery system and, consequently, the simultaneous administration of compounds. Characterization of nanoparticles properties, specifically involves quantification of the active pharmaceutical ingredients and is pivotal in the development of innovative nanomedicines. Therefore, this study has proposed and validated a new RP-HPLC-UV method for the simultaneous determination of simvastatin and coenzyme Q10 in hybrid nanoparticles systems. A reversed phase (RP) C8 column and a gradient elution of water: methanol at flow rate of 1.5 ml/min was used. Simvastatin (SVT), simvastatin hydroxyacid isoform (SVA) and coenzyme Q10 were identified by dual wavelength-UV detection at 238 nm (statins) and 275 nm, respectively. The proposed method was selective and linear in the range of 0.5-25 µg/ml (r2 > 0.999), precise, with values of relative standard deviation (RSD) lower than 2%, robust and accurate (recovery values of 100 ±â€¯5%), satisfying FDA guidelines. Furthermore, low detection (LOD <0.2 µg/ml) and quantification limits (LOQ <0.4 µg/ml) were suitable for the application of the method for the in vitro study of release kinetics of simvastatin and coenzyme Q10 co-encapsulated in lecithin/chitosan nanoparticles. The proposed method represents, to our knowledge, the only method for the simultaneous quantification of simvastatin, coenzyme Q10 and of the hydrolysed hydroxyacid isoform of the statin in nanoparticles.

Antiproliferative Activity and VEGF Expression Reduction in MCF7 and PC-3 Cancer Cells by Paclitaxel and Imatinib Co-encapsulation in Folate-Targeted Liposomes.

Co-encapsulation of anticancer drugs paclitaxel and imatinib in nanocarriers is a promising strategy to optimize cancer treatment. Aiming to combine the cytotoxic and antiangiogenic properties of the drugs, a liposome formulation targeted to folate receptor co-encapsulating paclitaxel and imatinib was designed in this work. An efficient method was optimized for the synthesis of the lipid anchor DSPE-PEG(2000)-folic acid (FA). The structure of the obtained product was confirmed by RMN, FT-IR, and ESI-MS techniques. A new analytical method was developed and validated for simultaneous quantification of the drugs by liquid chromatography. Liposomes, composed of phosphatidylcholine, cholesterol, and DSPE-mPEG(2000), were prepared by extrusion. Their surface was modified by post-insertion of DSPE-PEG(2000)-FA. Reaction yield for DSPE-PEG(2000)-FA synthesis was 87%. Liposomes had a mean diameter of 122.85 ± 1.48 nm and polydispersity index of 0.19 ± 0.01. Lyophilized formulations remained stable for 60 days in terms of size and drug loading. FA-targeted liposomes had a higher effect on MCF7 cell viability reduction (p < 0.05) when compared with non-targeted liposomes and free paclitaxel. On PC-3 cells, viability reduction was greater (p < 0.01) when cells were exposed to targeted vesicles co-encapsulating both drugs, compared with the non-targeted formulation. VEGF gene expression was reduced in MCF7 and PC-3 cells (p < 0.0001), with targeted vesicles exhibiting better performance than non-targeted liposomes. Our results demonstrate that multifunctional liposomes associating molecular targeting and multidrug co-encapsulation are an interesting strategy to achieve enhanced internalization and accumulation of drugs in targeted cells, combining multiple antitumor strategies.

Improved tacrolimus skin permeation by co-encapsulation with clobetasol in lipid nanoparticles: Study of drug effects in lipid matrix by electron paramagnetic resonance.

Combined therapy with corticosteroids and immunosuppressant-loaded nanostructured lipid carriers (NLC) could be useful in the treatment of skin diseases. To circumvent NLC loading capacity problems, loaded drugs should have different physicochemical characteristics, such as tacrolimus (TAC) and clobetasol (CLO). Therefore, in the present study, TAC and CLO were encapsulated in NLC (TAC-NLC, CLO-NLC and TAC+CLO-NLC), coated or otherwise with chitosan. Electron paramagnetic resonance (EPR) spectroscopy of different spin labels was used to investigate the impact of drug and oil incorporation on the lipid dynamic behavior of the lipid matrices. In addition, the impact of co-encapsulation on drug release and skin permeation was evaluated. Entrapment efficiency was greater than 90% for both drugs, even when the maximum drug loading achieved for TAC-NLC and CLO-NLC was kept at TAC+CLO-NLC, because TAC is more soluble in the solid lipid and CLO in the liquid lipid. EPR data indicated that both drugs reduced the lipid fluidity near the polar surface of the lipid matrix, which suggests their presence in this region. In addition, EPR data showed that liquid lipid is also present in more superficial regions of the nanoparticle matrix. CLO was released faster than TAC from TAC+CLO-NLC, probably because it is more soluble in the liquid lipid. TAC skin penetration was affected by CLO. A 5-fold increase in TAC penetration was observed from TAC+CLO-NLC when compared to TAC-NLC formulations. Coating also increased TAC and CLO permeation to deeper skin layers (1.8-fold and 1.6-fold, respectively). TAC+CLO-NLC seems to be an effective strategy for topical delivery of TAC and CLO, and thus constitutes promising formulations for the treatment of skin diseases.

Skin penetration behavior of lipid-core nanocapsules for simultaneous delivery of resveratrol and curcumin.

Polyphenols, which are secondary plant metabolites, gain increasing research interest due to their therapeutic potential. Among them, resveratrol and curcumin are two agents showing antioxidant, anti-inflammatory, antimicrobial as well as anticarcinogenic effects. In addition to their individual therapeutic effect, increased activity was reported upon co-delivery of the two compounds. However, due to the poor water solubility of resveratrol and curcumin, their clinical application is currently limited. In this context, lipid-core nanocapsules (LNC) composed of an oily core surrounded by a polymeric shell were introduced as drug carrier systems with the potential to overcome this obstacle. Furthermore, the encapsulation of polyphenols into LNC can increase their photostability. As the attributes of the polyphenols make them excellent candidates for skin treatment, the aim of this study was to investigate the effect of co-delivery of resveratrol and curcumin by LNC upon topical application on excised human skin. In contrast to the formulation with one polyphenol, resveratrol penetrated into deeper skin layers when the co-formulation was applied. Based on vibrational spectroscopy analysis, these effects are most likely due to interactions of curcumin and the stratum corneum, facilitating the skin absorption of the co-administered resveratrol. Furthermore, the interaction of LNC with primary human skin cells was analyzed encountering a cellular uptake within 24h potentially leading to intracellular effects of the polyphenols. Thus, the simultaneous delivery of resveratrol and curcumin by LNC provides an intelligent way for immediate and sustained polyphenol delivery for skin disease treatment.

Co-encapsulation of Daphnia magna and microalgae in silica matrices, a stepping stone toward a portable microcosm.

We report on the first silica encapsulation of a metazoan (Daphnia magna), with a high initial viability (96% of the population remained active 48 h after encapsulation). Moreover, the co-encapsulation of this crustacean and microalgae (Pseudokirchneriella subcapitata) was achieved, creating inside a silica monolith, the smallest microcosm developed to present. This artificial ecosystem in a greatly diminished scale isolated inside a silica nanoporous matrix could have applications in environmental monitoring, allowing ecotoxicity studies to be carried out in portable devices for on-line and in situ pollution level assessment.