Promising effect of propolis and a by-product on planktonic cells and biofilm formation by the main agents of human fungal infections.

Few antifungals available today are effective in treating biofilms. Thus, it is urgent to discover new compounds, such as natural products, that provide improvements to existing treatments or the development of new antifungal therapies. This study aimed to perform a comparative analysis between the green propolis extract (PE) and its by-product, a waste of propolis extract (WPE) through a screening with Candida sp., Fusarium sp. and Trichophyton sp. The antifungal property of PE and WPE was assessed by the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) determination in planktonic cells. The influence of both extracts on the inhibition of biofilm formation in these fungi was also tested. The WPE MIC and MFC values (68.75 to 275.0 µg/mL) were three to twelve times lower than the values obtained for PE (214.06 to 1712.5 µg/mL). PE was more efficient than WPE in inhibiting the biofilm initial phase, especially in C. albicans. Meanwhile, WPE had dose-dependent behavior for the three fungi, being more effective on filamentous ones. Both PE and WPE showed excellent antifungal activity on planktonic cells and demonstrated great efficacy for inhibiting biofilm formation in the three fungi evaluated.

Thermoresponsive Hydrogel-Loading Aluminum Chloride Phthalocyanine as a Drug Release Platform for Topical Administration in Photodynamic Therapy.

Phthalocyanine aluminum chloride (Pc) is a clinically viable photosensitizer (PS) to treat skin lesions worsened by microbial infections. However, this molecule presents a high self-aggregation tendency in the biological fluid, which is an in vivo direct administration obstacle. This study proposed the use of bioadhesive and thermoresponsive hydrogels comprising triblock-type Pluronic F127 and Carbopol 934P (FCarb) as drug delivery platforms of Pc (FCarbPc)-targeting topical administration. Carbopol 934P was used to increase the F127 hydrogel adhesion on the skin. Rheological analyses showed that the Pc presented a low effect on the hydrogel matrix, changing the gelation temperature from 27.2 ± 0.1 to 28.5 ± 0.9 °C once the Pc concentration increases from zero to 1 mmol L-1. The dermatological platform showed matrix erosion effects with the release of loaded Pc micelles. The permeation studies showed the excellent potential of the FCarb platform, which allowed the partition of the PS into deeper layers of the skin. The applicability of this dermatological platform in photodynamic therapy was evaluated by the generation of reactive species which was demonstrated by chemical photodynamic efficiency assays. The low effect on cell viability and proliferation in the dark was demonstrated by in vitro assays using L929 fibroblasts. The FCarbPc fostered the inhibition of Staphylococcus aureus strain, therefore demonstrating the platform's potential in the treatment of dermatological infections of microbial nature.

Thermo- and pH-Responsive Gelatin/Polyphenolic Tannin/Graphene Oxide Hydrogels for Efficient Methylene Blue Delivery.

Gelatin (GE), amino-functionalized polyphenolic tannin derivative (TN), and graphene oxide (GO) were associated to yield thermo- and pH-responsive hydrogels for the first time. Durable hydrogel assemblies for drug delivery purposes were developed using the photosensitizer methylene blue (MB) as a drug model. The cooling GE/TN blends provide brittle physical assemblies. To overcome this disadvantage, different GO contents (between 0.31% and 1.02% wt/wt) were added to the GE/TN blend at 89.7/10.3 wt/wt. FTIR and RAMAN spectroscopy analyses characterized the materials, indicating GO presence in the hydrogels. Incorporation studies revealed a total MB (0.50 mg/mL) incorporation into the GE/TN-GO hydrogel matrices. Additionally, the proposed systems present a mechanical behavior similar to gel. The GO presence in the hydrogel matrices increased the elastic modulus from 516 to 1650 Pa. SEM revealed that hydrogels containing MB present higher porosity with interconnected pores. Dissolution and swelling degree studies revealed less stability of the GE/TN-GO-MB hydrogels in SGF medium (pH 1.2) than SIF (pH 6.8). The degradation increased in SIF with the GO content, making the polymeric matrices more hydrophilic. MB release studies revealed a process controlled by Fickian diffusion. Our results point out the pH-responsible behavior of mechanically reinforced GE/TN-GO-MB hydrogels for drug delivery systems purposes.

Biomedical Platform Development of a Chlorophyll-Based Extract for Topic Photodynamic Therapy: Mechanical and Spectroscopic Properties.

Photodynamic therapy (PDT) is a therapeutic modality that has shown effectiveness in the inactivation of cancer cell lines and microorganisms. Treatment consists of activating the photosensitizer (PS) upon light irradiation of adequate wavelength. After reaching the excited state, the PS can handle the intersystem conversion through energy transfer to the molecular oxygen, generating reactive oxygen species. This especially applies to singlet oxygen (1O2), which is responsible for the selective destruction of the sick tissue. Photosensitizing compounds (chlorophylls and derivatives) existing in the spinach extract have applicability for PDT. This study aimed to develop and characterize the thermoresponsive bioadhesive system composed of Pluronic F127 20.0%- and Carbopol 934P 0.2% (w/w) (FC)-containing chlorophyll-based extract 0.5% (w/w) (FC-Chl). Mechanical and rheological properties, in vitro release, sol-gel transition temperature, and ex vivo permeability of the spinach extract PS components (through pig ear skin) were investigated. Furthermore, photodynamic activity of the system was accessed through uric acid and time-solved measurements. The sol-gel transition temperature obtained for the FC-Chl system was 28.8 ± 0.3 °C. Rheological and texture properties of the platform were suitable for use as a dermatological system, exhibiting easy application and good characteristics of retention in the place of administration. In vitro release studies showed the presence of two distinct mechanisms that reasonably obey the zero-order and first-order kinetics models. PS components presented skin permeability and reached a permeation depth of 830 µm (between the epidermis and dermis). The photodynamic evaluation of the FC-Chl system was effective in the degradation of uric acid. The quantum yield (ΦΔ1O2) and life time (τ1O2) of singlet oxygen showed similar values for the spinach extract and the isolated chlorophyll a species in ethanol. These results allowed for the classification of the FC-Chl platform as potentially useful for the delivery of the chlorophyll-based extract in the topic PDT, suggesting that it is worthy for in vivo evaluation.

Functional Polymeric Systems as Delivery Vehicles for Methylene Blue in Photodynamic Therapy.

Antibiotic-resistant microorganisms have become a global concern, and the search for alternative therapies is very important. Photodynamic therapy (PDT) consists of the use of a nontoxic photosensitizer (PS), light, and oxygen. This combination produces reactive oxygen species and singlet oxygen, which can alter cellular structures. Methylene blue (MB) is a substance from the phenothiazine class often used as a PS. In this work, to facilitate the PS contact within the wounds, we have used Design of Experiments 2(3) plus central point to develop functional polymeric systems. The formulations were composed by poloxamer 407 [15.0, 17.5, or 20.0% (w/w)], Carbopol 934P [0.15, 0.20, or 0.25% (w/w)], and MB [0.25, 0.50, or 0.75% (w/w)]. The sol-gel transition temperature, flow rheometry, in vitro MB release, and ex vivo study of MB cutaneous permeation and retention were investigated. Moreover, the evaluation of photodynamic activity was also analyzed by in vitro degradation of tryptophan by singlet oxygen and using Artemia salina. The determination of the gelation temperature displayed values within the range of 25-37 °C, and the systems with better characteristics were subjected to rheological analysis and in vitro release profiling. The 20/0.15/0.25 formulation showed the best release profile (42.57% at 24 h). This system displayed no significant skin permeation (0.38% at 24 h), and the photooxidation of tryptophan test showed the production of reactive species of oxygen. The toxicity test using A. salina revealed that the MB associated with the light increased the mortality rate by 61.29%. Therefore, investigating the PDT efficacy of the functional polymeric system containing MB will be necessary in the future.

Development and characterization of gelatin and ethylcellulose microparticles designed as platforms to delivery fluoride.

PURPOSE: To develop and characterize microparticles containing fluoride sources (FS) from sodium fluoride, sodium monofluorophosphate (MFP) or aminofluoride and evaluate their characteristics as fluoride delivery systems. METHODS: Ethylcellulose microparticles containing fluoride (EM) were prepared by emulsification of ethyl acetate dispersion containing polymer and FS (ethylcellulose:FS ratio of 1:0.25 wt/wt) with aqueous external phase containing polysorbate 80 (0.8% vol/vol) using the volume ratio (organic:aqueous) of 1:5. The organic solvent was evaporated; microparticles were collected by centrifuging, washed with deionized water and freeze-dried. Gelatin microparticles containing FS (GM) was obtained by dispersion of the natural polymer in water, adding FS (6:1 wt/wt) and 20% (wt/wt) of mannitol. The final dispersions were spray-dried. Particle morphology and size were investigated using optical microscopy. The content of fluoride ions in the microparticles was quantified using a potentiometric method. The encapsulation efficiency and in vitro release profile of fluoride was also determined. RESULTS: Microparticles exhibited polydispersity and mean diameters <145.35 and <124.22 µm for EM and GM, respectively. Considering the entrapment efficiency, the spray-drying technique exhibited greater values than microencapsulation by emulsification and solvent evaporation. The release profile of fluoride ions from microparticles was shown to be modified, fitted first order and guided by Fickian diffusion. CONCLUSIONS: Microparticles prepared with ethylcellulose or gelatin can be used as platform for oral delivery of fluoride, providing a means to increase the local supply of this ion in a controlled manner, providing an increased protection against caries. Moreover, further investigations are needed to demonstrate this property in vivo.

New approach to the use of propolis against dermatomycosis.

In recent years, propolis extract (PE) has demonstrated antimicrobial and anti-inflammatory properties. The aim of this study was to evaluate the antifungal activity of a bioadhesive thermoresponsive system containing 16% propolis (BTSP 16%) against Microsporum canis, Nannizzia gypsea, Trichophyton mentagrophytes and T. rubrum. We also evaluated PE alone against the same strains. The results showed that both PE and BTSP 16% significantly reduced the fungal viability of all evaluated strains. In addition, they interacted with the biofilm of these species in different stages of biofilm formation. We observed that the bioadhesive and thermoresponsive properties of BTSP 16% prolonged propolis presence at infection sites, leading to positive results against planktonic fungal cells and mature biofilms. These characteristics make this formulation a valuable alternative treatment for dermatomycosis.

Silver nanoparticles stabilized with propolis show reduced toxicity and potential activity against fungal infections.

Aim: Elucidate the antifungal efficacy of biologically synthesized silver nanoparticles with ethanolic propolis extract (AgNPs PE) against the planktonic forms and biofilms of clinically important fungi. Materials & methods: AgNPs were synthesized, characterized and evaluated for cytotoxicity, mutagenicity and antimicrobial activity. Results: AgNPs PE displayed a colloidal appearance, good stability and size of 2.0-40.0 nm. AgNPs PE demonstrated lower cytotoxicity and nonmutagenic potential. In addition, AgNPs PE displayed antifungal properties against all tested isolates, inhibiting growth at concentrations lower than the cytotoxic effect. Mature biofilms treated for 48 h with AgNPs PE showed significant reduction of viable cells, metabolic activity and total biomass. Conclusion: This is the first time that AgNPs have been synthesized from an ethanolic extract of propolis only, proving antifungal, antibiofilm, atoxic and nonmutagenic properties.

Propolis extract has bioactivity on the wall and cell membrane of Candida albicans.

ETHNOPHARMACOLOGICAL RELEVANCE: The use of natural products such as propolis extract (PE) is a promising alternative when topically administered to replace conventional antifungals, mostly due to its therapeutic applications, ease of access and low toxicity. However, despite being the subject of several mycology studies, they focus primarily on exploiting their antimicrobial activity, lacking information on the mechanisms of action of PE on Candida spp., characterizing its antifungal potential. AIM OF THE STUDY: To elucidate the bioactivity of PE on the cellular structure of Candida albicans. MATERIALS AND METHODS: A total of seven C. albicans clinical isolates plus a reference strain of C. albicans ATCC 90028 were used in this study. The PE was characterized and its effect on C. albicans was determined by susceptibility and growth kinetics assays; interference on C. albicans germination and filamentation; evaluation of the integrity of the C. albicans cell wall and membrane, as well as its mutagenic potential. RESULTS: The PE presented strong inhibitory activity, which showed its greatest antifungal activity at 12 h with dose and time dependent fungistatic characteristics, effectively inhibiting and interfering on C. albicans filamentation. In addition, PE caused membrane and cell wall damage with intracellular content extravasation. Moreover, PE was not mutagenic. CONCLUSIONS: The bioactivity of PE is mainly related to the loss of integrity membrane as well as the integrity of the cell wall and consequent increase in permeability, without mutagenic effects.

Properties of a commercial κ-carrageenan food ingredient and its durable superabsorbent hydrogels.

Physical kappa-carrageenan-based hydrogels are often prepared from dilute aqueous kappa-carrageenan (κ-carrageenan) solutions at the presence of metallic ions or by mixing these solutions with proteins and other polysaccharides. The κ-carrageenan hydrogels have been used for technological purposes; however, there are no reports about the properties of a commercial GENUGEL® κ-carrageenan produced by the CP Kelco. The flame atomic absorption spectrometry shows that the commercial κ-carrageenan comprises a high content of metallic ions (K+ = 216.1 g kg-1, Na+ = 6.3 g kg-1 and Ca2+ = 12.5 g kg-1). The X-ray photoelectron spectroscopy (XPS) indicates the presence of sodium, calcium, and potassium atoms on the as-received κ-carrageenan and its physical hydrogel surfaces. XPS supports the occurrence of a low protein content onto the sample surfaces, as well. The metallic level (especially for K+) in the commercial κ-carrageenan plays an essential role in the preparation of durable hydrogels. These materials are prepared by cooling aqueous κ-carrageenan solutions at 4.0 and 5.0 wt%. The gelation temperature is determined by measuring G' &G″ as a function of the temperature. The gelation behavior depends on the κ-carrageenan concentration, as well as the metallic content in the commercial sample. Scanning electron microscopy shows that hydrogels have porous and smooth surfaces. The dried materials swell from 2400 to 3100%, while the disintegration/dissolution test confirms that the samples present high stability in distilled water throughout 14 days. These hydrogels are superabsorbent materials and can be applied in agriculture as soil conditioners.

Photodynamic Therapy of Psoriasis Using Photosensitizers of Vegetable Origin.

Psoriasis is an immune-mediated, chronic and recurrent inflammatory skin disease, prevalent worldwide, and represents an important burden in life quality of patients. The most common clinical variant is termed as psoriasis vulgaris or plaque psoriasis, which with an individualized and carefully monitored therapy can decrease the patients' morbidity and improving their life quality. The aim is to achieve disease control, minimize the adverse drug effects, and tailor the treatment to individual patient factors. Photodynamic therapy (PDT) is based on local or systemic administration of a non-toxic photosensitizer followed by irradiation with a particular wavelength to generate reactive oxygen species (ROS), mainly highly cytotoxic singlet oxygen (1O2). The generation of these species results in the attack to substrates involved in biological cycles causing necrosis and apoptosis of affected tissues. Photosensitizers are found in natural products and also obtained by partial syntheses from abundant natural starting compounds. They can be isolated at low cost and in large amounts from plants or algae. Therefore, this manuscript reviews the use of molecules from vegetal sources as photosensitizer agents for the PDT of psoriasis. Psoriasis pathogenesis, management and treatment were reviewed. PDT principles, fundamentals and utilization for the treatment of psoriasis were also discussed. Photosensitizers for PDT of psoriasis are also reviewed focusing on those from vegetal sources. Despite the PDT is utilized for the treatment of psoriasis, very little amount of photosensitizers from plant sources are utilized, such as chlorophyll derivatives and hypericin; however, other natural photosensitizers such as curcumin, could also be investigated. They could constitute a very important, safe and cheap alternative for the successful photodynamic treatment of psoriasis.

Design and Characterization of Mucoadhesive Gelatin-Ethylcellulose Microparticles for the Delivery of Curcumin to the Bladder.

BACKGROUND: Bladder cancer is the second type of malignant carcinoma of the urinary tract. The treatment is time-consuming and requires maintenance doses of the drug for long period of time with important side effects. Curcumin has shown evident clinical advances in the treatment of cancer. The technology of microencapsulation and the use of mucoadhesive materials can contribute to modify the delivery and improve the bioavailability of curcumin. OBJECTIVE: The aim of this study was to design and characterize mucoadhesive microparticles containing curcumin using multivariate analysis and the spray-drying technique. METHODS: A factorial design 32+1 was employed to investigate the influence of gelatin, ethylcellulose, and curcumin on size, polydispersity index, drug content and entrapment efficiency. Microparticles were also evaluated by ATR-FTIR, X-ray diffraction, antioxidant activity, in-vitro release profile, exvivo mucoadhesion performance, and in-vitro cytotoxicity. RESULTS: Microparticles showed non-uniform surface, mean diameter from 2.73 µm to 4.62 µm and polydispersity index from 0.72 to 1.09, according to the different combinations of the independent factors. These independent variables also had a significant effect on the drug content. The highest values of drug trapping efficiency were obtained with the highest concentration of curcumin and polymers. Formulations displayed slow drug release and important antioxidant activity. The good mucoadhesive performance of microparticles was assessed by the falling film technique. Moreover, the formulations did not display in vitro toxicity against Artemia salina and Fibroblasts LM(TK). CONCLUSION: The design results were useful for developing of curcumin dosage form with good physicochemical characteristics and mucoadhesive properties for the bladder administration.

Artepillin C Induces Selective Oxidative Stress and Inhibits Migration and Invasion in a Comprehensive Panel of Human Cervical Cancer Cell Lines.

BACKGROUND: Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) is the main bioactive component of Brazilian green propolis, and possesses, among other things, anticancer properties. However, to the best of our knowledge, there are no studies of artepillin C in cervical cancer. METHOD: To explore a new therapeutic candidate for cervical cancer, we have evaluated the effects of artepillin C on cellular viability in a comprehensive panel of human cervical cancer-derived cell lines including HeLa (human papillomavirus/HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16- and 18-positive) and C33A (HPV-negative) cells compared to a spontaneously immortalized human epithelial cell line (HaCaT). RESULTS: Our results demonstrated that artepillin C had a selective effect on cellular viability and could induce apoptosis possibly by intrinsic pathway, likely a result of oxidative stress, in all cancer-derived cell lines but not in HaCaT. Additionally, artepillin C was able to inhibit the migration and invasion of cancer cells. CONCLUSION: Thus, artepillin C appears to be a promising new candidate as an anticancer drug for cervical cancer induced by different HPV types.

Propolis Extract for Onychomycosis Topical Treatment: From Bench to Clinic.

Onychomycosis is a chronic fungal infection of nails, commonly caused by dermatophyte fungi, primarily species of Trichophyton. Because of the limited drug arsenal available to treat general fungal infections and the frequent failure of onychomycosis treatment, the search for new therapeutic sources is essential, and topical treatment with natural products for onychomycosis has been encouraged. Propolis, an adhesive resinous compound produced by honeybees (Apis mellifera), has shown multiple biological properties including significant antifungal and anti-biofilm activities in vitro. In spite of promising in vitro results, in vivo results have not been reported so far. This study assessed an ethanol propolis extract (PE) as a topical therapeutic option for onychomycosis, including its characterization in vitro and its applicability as a treatment for onychomycosis (from bench to clinic). The in vitro evaluation included analysis of the cytotoxicity and the antifungal activity against the planktonic cells and biofilm formed by Trichophyton spp. We also evaluated the capacity of PE to penetrate human nails. Patients with onychomycosis received topical PE treatments, with a 6-month follow-up period. The results of the in vitro assays showed that PE was non-toxic to the cell lines tested, and efficient against both the planktonic cells and the biofilm formed by Trichophyton spp. The results also showed that PE is able to penetrate the human nail. The results for PE applied topically to treat onychomycosis were promising, with complete mycological and clinical cure of onychomycosis in 56.25% of the patients. PE is an inexpensive commercially available option, easy to obtain and monitor. Our results indicated that PE is a promising natural compound for onychomycosis treatment, due to its ability to penetrate the nail without cytotoxicity, and its good antifungal performance against species such as Trichophyton spp. that are resistant to conventional antifungals, both in vitro and in patients.

Semisolid systems containing propolis for the treatment of periodontal disease: in vitro release kinetics, syringeability, rheological, textural, and mucoadhesive properties.

Formulations containing poloxamer 407 (P407), carbopol 934P (C934P), and propolis extract (PE) were designed for the treatment of periodontal disease. Gelation temperature, in vitro drug release, rheology, hardness, compressibility, adhesiveness, mucoadhesion, and syringeability of formulations were determined. Propolis release from formulations was controlled by the phenomenon of relaxation of polymer chains. Formulations exhibited pseudoplastic flow and low degrees of thixotropy or rheopexy. In most samples, increasing the concentration of C934P content significantly increased storage modulus (G'), loss modulus (G''), and dynamic viscosity (eta'), at 5 degrees C, G'' exceeded G'. At 25 and 37 degrees C, eta' of each formulation depended on the oscillatory frequency. Formulations showed thermoresponsive behavior, existing as a liquid at room temperature and gel at 34-37 degrees C. Increasing the C934P content or temperature significantly increased formulation hardness, compressibility, and adhesiveness. The greatest mucoadhesion was noted in the formulation containing 15% P407 (w/w) and 0.25% C934P (w/w). The work of syringeability values of all formulations were similar and very desirable with regard to ease of administration. The data obtained in these formulations indicate a potentially useful role in the treatment of periodontitis and suggest they are worthy of clinical evaluation.

A mucosa-mimetic material for the mucoadhesion testing of thermogelling semi-solids.

Mucosa-mimetic materials are synthetic substrates which aim to replace animal tissue in mucoadhesion experiments. One potential mucosa-mimetic material is a hydrogel comprised of N-acryloyl-d-glucosamine and 2-hydroxyethylmethacrylate, which has been investigated as a surrogate for animal mucosae in the mucoadhesion testing of tablets and solution formulations. This study aims to investigate the efficacy of this mucosa-mimetic material in the testing of thermogelling semi-solid formulations, which transition from solution to gel upon warming. Two methods for assessing mucoadhesion have been used; tensile testing and a flow-through system, which allow for investigation under dramatically different conditions. It was found that the mucosa-mimetic material was a good surrogate for buccal mucosa using both testing methods. This material may be used to replace animal tissue in these experiments, potentially reducing the number of laboratory animals used in studies of this type.

Environmentally Responsive Systems for Drug Delivery.

BACKGROUND: In recent decades, the development of the environmentally responsive systems for drug delivery has been well regarded, with enormous potential in different applications. <P><P> Methods: These environmentally sensitive, smart, intelligent formulations have the ability to alter their physical properties in response to small changes in physical or chemical conditions, such as temperature, glucose, pH, ultrasound, light, electric field and redox potential with a huge potential in drug delivery systems. The use of formulations containing smart materials enables to carry the drug to the target tissue, cells and release in a triggered way. Consequently, they have demonstrated several advantages like decreased dose frequency, ease of preparation and administration, prolonged release with reduced side effects, as well as, reduced costs when compared to conventional processes for industrial applications. In this sense, many patents have deposited, displaying different pharmaceutical devices using responsive systems. <P><P> Results: There are more than twenty-five patents deposited about thermoresponsive systems. Furthermore, a few number of patents within glucose responsive, ultrasound responsive and light responsive deposited. There also are about eight patents that are pH-responsive, four as electric-field responsive. Most of them cover more than one type of stimuli. <P><P> Conclusion: Therefore, in this review, since 1975 to 2016, we have categorized, reviewed and discussed the patents, applications, pharmaceutical dosage forms, the importance and perspectives of this environmentally responsive approach as potentially useful therapeutic modality.

Oxidative Stress Triggered by Apigenin Induces Apoptosis in a Comprehensive Panel of Human Cervical Cancer-Derived Cell Lines.

Recently, the cytotoxic effects of apigenin (4',5,7-trihydroxyflavone), particularly its marked inhibition of cancer cell viability both in vitro and in vivo, have attracted the attention of the anticancer drug discovery field. Despite this, there are few studies of apigenin in cervical cancer, and these studies have mostly been conducted using HeLa cells. To evaluate the possibility of apigenin as a new therapeutic candidate for cervical cancer, we evaluated its cytotoxic effects in a comprehensive panel of human cervical cancer-derived cell lines including HeLa (human papillomavirus/HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and HPV 18-positive), and C33A (HPV-negative) cells in comparison to a nontumorigenic spontaneously immortalized human epithelial cell line (HaCaT). Our results demonstrated that apigenin had a selective cytotoxic effect and could induce apoptosis in all cervical cancer cell lines which were positively marked with Annexin V, but not in HaCaT (control cells). Additionally, apigenin was able to induce mitochondrial redox impairment, once it increased ROS levels and H2O2, decreased the Δψm, and increased LPO. Still, apigenin was able to inhibit migration and invasion of cancer cells. Thus, apigenin appears to be a promising new candidate as an anticancer drug for cervical cancer induced by different HPV genotypes.

The Use of Propolis in Micro/Nanostructured Pharmaceutical Formulations.

BACKGROUND: Propolis is a resinous material with complex chemical structure, produced by bees using plant sources, displaying a wide spectrum of biological activities. METHODS: Many studies have reported the use of this compound in pharmaceutical, medicinal, veterinary and dentistry areas, and the results have reported its pharmacological activities. RESULTS: Moreover, many propolis delivery systems have been proposed and evaluated, indicating that they can be used. On the other hand, considering its chemical and physical characteristics, propolis could be used as a material to produce micro/nano-structured pharmaceutical formulations. CONCLUSION: This work reviews the recent studies of development of micro/nanostructured systems using propolis or its byproduct. In addition, patents were reviewed and categorized.