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1.
J AOAC Int ; 106(6): 1438-1442, 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37672013

ABSTRACT

BACKGROUND: Hypericin (HYP) is a natural compound widely used as a food supplement. The encapsulation of HYP into nanosystems, such as nanostructured lipid carriers (NLC), is a promising strategy for delivering this lipophilic molecule and protecting it from degradation. OBJECTIVE: This study aims to develop and validate an analytical method to quantify the encapsulation efficiency of HYP in NLC. METHOD: A reverse-phase high-performance liquid chromatography (HPLC) method was developed and validated according to the International Conference on Harmonization (ICH) guide Q2 (R1). NLC was prepared through the ultrasonication method, and HYP encapsulation efficiency was evaluated using the validated method. RESULTS: Separation was achieved using an isocratic mobile phase composed of acetonitrile, methanol, and ammonium acetate buffer (10 mM, pH 5.0) (54:36:10, v/v/v) and a reverse stationary phase. The specificity, linearity, precision, accuracy, and robustness of the method were assessed and confirmed during the validation. Furthermore, the validated method was able to determine the encapsulation efficiency of HYP in NLC. CONCLUSIONS: The HPLC method was validated, and the results indicated the ability of NLC to deliver HYP compounds for further application as a food supplement. HIGHLIGHTS: HYP is used as a food supplement and for photodynamic therapy (PDT). The developed method was specific, linear, precise, accurate, and robust. NLCs showed a high ability to encapsulate HYP.


Subject(s)
Nanostructures , Limit of Detection , Nanostructures/chemistry , Chromatography, High Pressure Liquid/methods , Lipids
2.
Pharmaceuticals (Basel) ; 16(8)2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37631009

ABSTRACT

BACKGROUND: Vulvovaginal candidiasis (VVC) is a worldwide public health problem caused predominantly by the opportunistic polymorphic fungus Candida albicans, whose pathogenicity is associated with its morphological adaptability. To potentiate the treatment of C. albicans-induced VVC by an alternative method as photodynamic therapy (PDT), hypericin (Hy), a potent photosensitizer compound was incorporated into a nanostructured lipid carrier (NLC) and dispersed in hydrogel (HG). METHODS: After preparation of the sonication process, an NLC loaded with Hy was dispersed in HG based on Poloxamer 407 and chitosan obtaining Hy.NLC-HG. This hydrogel system was physically and chemically characterized and its in vitro and in vivo photodynamic and antifungal effects were evaluated. RESULTS: Through scanning electron microscopy, it was possible to observe a hydrogel system with a porous polymeric matrix and irregular microcavities. The Hy.NLC-HG system showed mucoadhesive properties (0.45 ± 0.08 N) and a satisfactory injectability (15.74 ± 4.75 N.mm), which indicates that it can be easily applied in the vaginal canal, in addition to a controlled and sustained Hy release profile from the NLC-HG of 28.55 ± 0.15% after 720 min. The in vitro antibiofilm assay significantly reduced the viability of C. albicans (p < 0.001) by 1.2 log10 for Hy.NLC-HG/PDT and 1.9 log10 for PS/PDT, Hy.NLC/PDT, and free RB/PDT, compared to the PBS/PDT negative control. The in vivo antifungal evaluation showed that animals treated with the vaginal cream (non-PDT) and the PDT-mediated Hy.NLC-HG system showed a significant difference of p < 0.001 in the number of C. albicans colonies (log) in the vaginal canal, compared to the inoculation control group. CONCLUSIONS: Thus, we demonstrate the pharmaceutical, antifungal, and photodynamic potential of hydrogel systems for Hy vaginal administration.

3.
Lasers Med Sci ; 37(8): 3183-3191, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35723829

ABSTRACT

This study aims to develop and characterize NCL loaded with ZnF16Pc (Pc) for application in antimicrobial photodynamic therapy. For the development of the NLC, the fusion-emulsification technique followed by sonication was applied. NLC and Pc-NLC were characterized in terms of mean diameter (Dm.n), polydispersity index (PdI), zeta potential (ZP), encapsulation efficiency (%EE), transmission electron microscopy (TEM), differential scanning (DSC), photobleaching and singlet oxygen generation in cellular systems (SOSG), and in vitro release assays performed by the beaker method, using dialysis membranes. Cell viability was performed by colony forming units (CFU/mL). The mean size of NLC and Pc-NLC was 158 nm ± 1.49 to 161.80 nm and showed PdI < 0.3 and ZP between -17.8 and -19.9, and stable during storage time (90 days). The TEM presented spherical particles, the Pc-NLC promoted the encapsulation of 75.57% ± 0.58. DSC analysis confirmed that there was no incompatibility between Pc and NLC. The analysis of the photodegradation profile proved to be photostable after encapsulation and this corroborates the data obtained by SOSG. In vitro release showed controlled and prolonged release. PDT Pc-NLC exhibited greater antifungal effect against C. albicans (3 log10 reduction) than Pc-NLC without light (1 log10 reduction). NLC can be an alternative to the application of Pc and improve the effect during PDT treatment.


Subject(s)
Candida albicans , Nanostructures , Antifungal Agents/pharmacology , Drug Carriers/chemistry , Drug Carriers/pharmacology , Indoles , Lipids/chemistry , Nanostructures/chemistry , Organometallic Compounds , Particle Size , Singlet Oxygen
4.
J Mycol Med ; 32(4): 101296, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35660541

ABSTRACT

INTRODUCTION AND AIM: The indiscriminate use and adverse effects of the main conventional antifungal agents compromise the effectiveness of treating vulvovaginal candidiasis (VVC), mainly caused by the species Candida albicans. This study evaluated the effectiveness of photodynamic therapy (PDT) and the in vitro and in vivo anti-candida potential of the hypericin (HYP)-loaded nanostructured lipid carriers (NLC). MATERIALS AND METHODS: Empty NLC and NLC-HYP were characterized by the dynamic light scattering technique and transmission electron microscopy to evaluate the average particle size distribution and its morphologies. The in vitro inhibition photodynamic effect of the systems was tested to reduce the planktonic viability of C. albicans. The therapeutic assay photodynamic of the systems was performed to treat VVC in mice. RESULTS: Empty NLC and NLC-HYP presented values of average hydrodynamic diameter, polydispersity index, and ζ-potential from 136 to 133 nm, 0.16 to 0.22, and -18 to -30 mV, respectively, on day 30. Microscopically, the systems showed spherical morphologies and nanoscale particles. Furthermore, in the in vitro inhibition assay, the treatment of PDT with NLC-HYP (NLC-HYP+) showed a significant reduction of the C. albicans planktonic viability compared to YNB negative control after 5 min of LED light irradiation. In the in vivo therapeutic assay, the antifungal group (vaginal antifungal cream) and NLC-HYP+ evaluated in the dark and by PDT, respectively, had a significant log10 reduction in fungal burden compared to the infected group on day 8 of the VVC treatment. CONCLUSION: Due to the in vitro and in vivo anti-candida potential, PDT-mediated systems can be an effective strategy in VVC therapy.


Subject(s)
Candidiasis, Vulvovaginal , Photochemotherapy , Humans , Female , Mice , Animals , Candidiasis, Vulvovaginal/drug therapy , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Candida albicans , Candida , Lipids/pharmacology , Lipids/therapeutic use
5.
Curr Med Chem ; 29(31): 5212-5229, 2022 Aug 15.
Article in English | MEDLINE | ID: mdl-35352643

ABSTRACT

Cephalosporins are ß-lactam antibiotics, classified into five generations and extensively used in clinical practice against infections caused by Gram-negative pathogens, including Enterobacteriaceae and P. aeruginosa. Commercially, conventional pharmaceutical forms require high doses to ensure clinical efficacy. Additionally, ß-lactam resistance mechanisms, such as the production of enzymes (called extended-spectrum ß-lactamases) and the low plasma half-life of these antibiotics, have been challenging in clinical therapy based on the use of cephalosporins. In this context, its incorporation into nanoparticles, whether organic or inorganic, is an alternative to temporally and spatially control the drug release and improve its pharmacokinetic and pharmacodynamic limitations. Considering this, the present review unites the cephalosporins encapsulated into organic and inorganic nanoparticles against resistant and nonresistant enterobacteria. We divide cephalosporin generation into subtopics in which we discuss all molecules approved by regulatory agencies. In addition, changes in the side chains at positions R1 and R2 of the central structure of cephalosporins for all semisynthetic derivatives developed were discussed and presented, as the changes in these groups are related to modifications in pharmacological and pharmacokinetic properties, respectively. Ultimately, we exhibit the advances and differences in the release profile and in vitro activity of cephalosporins incorporated in different nanoparticles.


Subject(s)
Anti-Bacterial Agents , Cephalosporins , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cephalosporins/pharmacology , Cephalosporins/therapeutic use , Gram-Negative Bacteria , Humans , Microbial Sensitivity Tests , Pseudomonas aeruginosa
6.
J Microencapsul ; 39(1): 61-71, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34984941

ABSTRACT

This study aimed to encapsulate and characterise a potential anti-tuberculosis copper complex (CuCl2(INH)2.H2O:I1) into polymeric nanoparticles (PNs) of polymethacrylate copolymers (Eudragit®, Eu) developed by nanoprecipitation method. NE30D, S100 and, E100 polymers were tested. The physicochemical characterisations were performed by DLS, TEM, FTIR, encapsulation efficiency and, in vitro release studies. Encapsulation of I1 in PN-NE30D, PN-E100, and PN-S100 was 26.3%, 94.5%, 22.6%, respectively. The particle size and zeta potentials were 82.3 nm and -24.5 mV for PNs-NE30D, 304.4 nm and +18.7 mV for PNs-E100, and 517.9 nm and -6.9 mV for PNs-S100, respectively. All PDIs were under 0.5. The formulations showed an I1 controlled release at alkaline pH with 29.7% from PNs-NE30D, 7.9% from PNs-E100 and, 28.1% from PNs-S100 at 1 h incubation. PNs were stable for at least 3 months. Particularly, PNs-NE30D demonstrated moderate inhibition of M. tuberculosis and low cytotoxic activity. None of the PNs induced mutagenicity.


Subject(s)
Copper , Nanoparticles , Anti-Bacterial Agents , Copper/pharmacology , Mutagens , Particle Size , Polymers
7.
Pharmaceutics ; 13(5)2021 May 08.
Article in English | MEDLINE | ID: mdl-34066727

ABSTRACT

Vulvovaginal candidiasis (VVC) is a vulvar/vaginal infection that affects approximately 75% of women worldwide. The current treatment consists of antimicrobials with hepatotoxic properties and high drug interaction probabilities. Therefore, this study aimed to develop a new treatment to VVC based on micelles containing curcumin (CUR) dispersed in a ureasil-polyether (U-PEO) hybrid. The physical-chemical characterization was carried out in order to observe size, shape, crystallinity degree and particle dispersion in the formulation and was performed by dynamic light scattering (DLS), scanning electron microscopy (SEM), X-ray diffraction (XRD) and through in vitro release study. The results of DLS and SEM exhibited micelles with 35 nm, and encapsulation efficiency (EE) results demonstrated 100% of EE to CUR dispersed in the U-PEO, which was confirmed by the DRX. The release results showed that CUR loaded in U-PEO is 70% released after 10 days, which demonstrates the potential application of this material in different pharmaceutical forms (ovules and rings), and the possibility of multidose based on a single application, suggesting a higher rate of adherence.

8.
Med Mycol ; 59(8): 821-827, 2021 Jul 14.
Article in English | MEDLINE | ID: mdl-33626136

ABSTRACT

The present study reports the performance of the pigment hypericin (HYP)-loaded poloxamer-based mucoadhesive in situ gelling liquid crystalline precursor system (LCPS) for the treatment of vulvovaginal candidiasis (VVC) in mice. LCPS composed of 40% of ethoxylated and propoxylated cetyl alcohol, 30% of oleic acid and cholesterol (7:1), 30% of a dispersion of 16% poloxamer 407 and 0.05% of HYP (HYP-LCPS) was prepared and characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS) and ex vivo permeation and retention studies across vaginal porcine mucosa were performed. In addition, the antifungal properties of the HYP-LCPS were evaluated in a murine in vivo model; for this, infected C57BL female mice groups were treated with both HYP in solution and HYP-LCPS, and after 6 days colony forming unit (CFU)/ml count was performed. PLM and SAXS confirmed that HYP-LCPS is a microemulsion situated in boundary transition region confirming its action as an LCPS. When in contact with simulated vaginal fluid, HYP-LCPS became rigid and exhibited maltase crosses and bragg peaks characteristics of lamellar phase. Ex vivo permeation and retention studies showed that HYP-LCPS provides a localized treatment on the superficial layers of porcine vaginal mucosa. HYP-LCPS induced a significant reduction in the number of CFU/ml in the mice; thus this formulation indicated it is as effective as a commercial dosage form. It was concluded that LCPS maintains the biological activity of HYP and provides an adequate drug delivery system for this lipophilic molecule at the vaginal mucosa, being a promising option in cases of VVC.


Subject(s)
Anthracenes/administration & dosage , Antifungal Agents/administration & dosage , Candida albicans/drug effects , Candidiasis, Vulvovaginal/drug therapy , Perylene/analogs & derivatives , Vagina/metabolism , Adhesives/administration & dosage , Animals , Anthracenes/metabolism , Antifungal Agents/metabolism , Chromatography, High Pressure Liquid , Disease Models, Animal , Female , Mice , Mice, Inbred C57BL , Microscopy, Polarization , Mucous Membrane/metabolism , Mucous Membrane/microbiology , Mucous Membrane/pathology , Perylene/administration & dosage , Perylene/metabolism , Poloxamer/administration & dosage , Radiation-Sensitizing Agents , Scattering, Small Angle , Swine , Vagina/microbiology , Vagina/pathology , X-Ray Diffraction
9.
Photodiagnosis Photodyn Ther ; 32: 102032, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33017659

ABSTRACT

Phthalocyanines are second-generation photosensitizers with photophysical and photochemical properties improved, in comparison to the first-generation. Also, these have shown to be phototoxic against several types of microorganisms and tumor cells. However, challenges such as low solubility in the physiological environment make its single administration unfeasible. Therefore, this review discusses a unique combination of phthalocyanine-loaded in drug delivery carriers for photodynamic therapy in different pathologies' treatment, including nanoemulsion, liposomes, and lipid nanoparticles in an attempt to overcome low solubility drawback. Furthermore, the latest advances to elucidating its mechanisms of action are shown. Subsequently, the manuscript was divided into ten different types of phthalocyanines for medical applications, with a description of their definitions and applications, summarizing the latest preclinical results founded in recent literature.


Subject(s)
Indoles , Photochemotherapy , Photosensitizing Agents , Indoles/pharmacology , Indoles/therapeutic use , Isoindoles , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Prospective Studies
10.
Pharmaceutics ; 12(8)2020 Jul 23.
Article in English | MEDLINE | ID: mdl-32718016

ABSTRACT

Bacterial resistance has become an important public health problem. Bacteria have been acquiring mechanisms to resist the action of antimicrobial active pharmaceutical ingredients (API). Based on this, a promising alternative is the use of nanotechnology, since when the systems are presented in nanometric size, there is an increase in the interaction and concentration of the action at the target site improving the activity. Thus, this study aims to develop a polymeric nanoparticle (PN) composed of chitosan and hydroxypropylmethylcellulose, as an innovative strategy for the administration of an association between ceftriaxone and extract of S. brasiliensis, for the treatment of Enterobacteriaceae. From a Box-Behnken design, nanoparticles were obtained and evaluated using the DLS technique, obtaining the particle size between 440 and 1660 nm, IPD from 0.42 to 0.92, and positive charges. Morphological characteristics of PN by SEM revealed spherical morphology and sizes similar to DLS. Infrared spectroscopy showed no chemical interaction between the components of the formulation. The broth microdilution technique evaluated their antimicrobial activity, and a considerable improvement in the activity of the extract and the API compared to the free compounds was found, reaching an improvement of 133 times in the minimum inhibitory activity CRO.

11.
Mater Sci Eng C Mater Biol Appl ; 108: 110462, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31923986

ABSTRACT

Breast cancer is a serious public health problem that causes thousands of deaths annually. Chemotherapy continues to play a central role in the management of breast cancer but is associated with extreme off-target toxicity. Therefore, treatments that directly target the tumor and display reduced susceptibility to resistance could improve the outcome and quality of life for patients suffering from this disease. Photodynamic therapy is a targeted treatment based on the use of light to activate a photosensitizer (PS) that then interacts with molecular oxygen and other biochemical substrates to generate cytotoxic levels of Reactive Oxygen Species. Currently approved PS also tends to have poor aqueous solubility that can cause problems when delivered intravenously. In order to circumvent this limitation, in this manuscript, we evaluate the potential of a phthalocyanine-loaded nanostructured lipid carrier (NLC) functionalized with folic acid (FA). To prepare the FA labelled NLC, the polymer PF127 was first esterified with FA and emulsified with an oil phase containing polyoxyethylene 40 stearate, capric/caprylic acid triglycerides, ethoxylated hydrogenated castor oil 40 and the PS zinc phthalocyanine. The resulting PS loaded FA-NLC had a hydrodynamic diameter of 180 nm and were stable in suspension for >90 days. Interestingly, the amount of singlet oxygen generated upon light activation for the PS loaded FA-NLC was substantially higher than the free PS, yet at a lower PS concentration. The PS was released from the NLC in a sustained manner with 4.13 ±â€¯0.58% and 27.7 ±â€¯3.16% after 30 min and 7 days, respectively. Finally, cytotoxicity assays showed that NLC in the concentrations of 09.1 µM of PS present non-toxic with >80 ±â€¯6.8% viable and after 90 s of the light-exposed the results show a statistically significant decrease in cell viability (57 ±â€¯4%). The results obtained allow us to conclude that the functionalized NLC incorporated with PS associated with the PDT technique have characteristics that make them potential candidates for the alternative treatment of breast cancer.


Subject(s)
Drug Carriers , Folic Acid , Indoles , Lipids , Nanostructures , Neoplasms/drug therapy , Photochemotherapy , Drug Carriers/chemical synthesis , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Carriers/pharmacology , Folic Acid/chemistry , Folic Acid/pharmacokinetics , Folic Acid/pharmacology , Humans , Indoles/chemistry , Indoles/pharmacokinetics , Indoles/pharmacology , Isoindoles , Lipids/chemistry , Lipids/pharmacokinetics , Lipids/pharmacology , MCF-7 Cells , Nanostructures/chemistry , Nanostructures/therapeutic use , Neoplasms/metabolism , Neoplasms/pathology , Poloxamer/chemistry , Poloxamer/pharmacokinetics , Poloxamer/pharmacology
12.
Curr Med Chem ; 27(22): 3623-3656, 2020.
Article in English | MEDLINE | ID: mdl-31232233

ABSTRACT

Colloidal carriers diverge depending on their composition, ability to incorporate drugs and applicability, but the common feature is the small average particle size. Among the carriers with the potential nanostructured drug delivery application there are SLN and NLC. These nanostructured systems consist of complex lipids and highly purified mixtures of glycerides having varying particle size. Also, these systems have shown physical stability, protection capacity of unstable drugs, release control ability, excellent tolerability, possibility of vectorization, and no reported production problems related to large-scale. Several production procedures can be applied to achieve high association efficiency between the bioactive and the carrier, depending on the physicochemical properties of both, as well as on the production procedure applied. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes Lipid-based nanocarriers (LNCs) versatile delivery system for various routes of administration. The route of administration has a significant impact on the therapeutic outcome of a drug. Thus, the non-invasive routes, which were of minor importance as parts of drug delivery in the past, have assumed added importance drugs, proteins, peptides and biopharmaceuticals drug delivery and these include nasal, buccal, vaginal and transdermal routes. The objective of this paper is to present the state of the art concerning the application of the lipid nanocarriers designated for non-invasive routes of administration. In this manner, this review presents an innovative technological platform to develop nanostructured delivery systems with great versatility of application in non-invasive routes of administration and targeting drug release.


Subject(s)
Nanoparticles , Nanostructures , Administration, Cutaneous , Drug Carriers , Drug Delivery Systems , Lipids , Particle Size
13.
Mol Pharm ; 15(10): 4491-4504, 2018 10 01.
Article in English | MEDLINE | ID: mdl-30184431

ABSTRACT

Vulvovaginal candidiasis (VVC) is the most common infection caused by Candida albicans and greatly reduces the quality of life of women affected by it. Due to the ineffectiveness of conventional treatments, there is growing interest in research involving compounds of natural origin. One such compound is curcumin (CUR), which has been proven to be effective against this microorganism. However, some of CUR's physicochemical properties, especially its low aqueous solubility, make the therapeutic application of this compound difficult. Thus, the incorporation of CUR in mucoadhesive liquid crystalline systems (MLCSs) for vaginal administration may be an efficient strategy for the treatment of VVC. MLCSs are capable of potentiating the compound's action, releasing it in a controlled manner, and can enable longer exposure at the site of infection. In this study, MLCSs consisting of oleic acid and ergosterol 5:1 (w/w) as the oily phase, PPG-5-CETETH-20 as the surfactant, and a polymer dispersion of 1% chitosan as the aqueous phase, were developed for the application of CUR (MLCS-CUR) in VVC treatment. The formulations were characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), oscillatory rheometry, continuous shear rheometry, texture profile analysis, and in vitro mucoadhesion. In addition, the antimicrobial activity was evaluated in vitro, and the effects on local fungal burden and cytokine profiles were investigated in a murine model of VVC. PLM and SAXS showed that the developed formulations presented a characteristic of a microemulsion. However, after the addition of artificial vaginal mucus (AVM), PLM showed that the formulations had structures similar to the "Maltese cross" characteristic of lamellar MLCS. Mucoadhesive test results showed an increase in the mucoadhesive strength of these formulations. Rheology analyses suggested long-lasting action of the formulation at the infected site. The in vitro antimicrobial activity assays suggested that CUR possesses antifungal activity against Candida albicans, determined after its incorporation into the MLCS. Further, MLCS-CUR was also more effective in vivo in the control of vaginal infection than treatment with fluconazole. Immunological assays showed that the ratio of pro-inflammatory (IL-1ß) to anti-inflammatory (TGF-ß) cytokines has decreased and that there is a reduction in the number of polymorphonuclear neutrophils recruited to the vaginal lumen, showing that treatment with MLCS-CUR was effective in modulating the inflammatory reaction associated with the infection. The results suggest that MLCSs could potentially be used in the treatment of VVC with CUR.


Subject(s)
Candidiasis, Vulvovaginal/drug therapy , Curcumin/pharmacology , Curcumin/therapeutic use , Liquid Crystals/chemistry , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Candida albicans/drug effects , Candida albicans/pathogenicity , Cell Line , Curcumin/chemistry , Drug Liberation , Female , Humans , Vagina/microbiology
14.
AAPS PharmSciTech ; 19(3): 1401-1409, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29404955

ABSTRACT

Trans-resveratrol (RSV) is a natural compound with several properties, such as the ability to inhibit the tyrosinase enzyme, with potential application as a skin-lightning agent and for the treatment of skin disorders associated with hyperpigmentation and melanogenesis. However, the drug faces several drawbacks which altogether limit its therapeutic application. Thus, drug loading into nanocarriers emerge as an alternative to circumvent these problems. Herein, nanostructured lipid carriers (NLCs) have been employed for RSV encapsulation, with comparison of two different lipids, glyceryl behenate (more hydrophobic), and polyoxyethylene 40 (PEG 40) stearate. PEG 40 stearate-containing NLCs presented smaller particle size and polydispersity compared with glyceryl behenate, attributed to better emulsification and nanoparticle formation, resulting in higher RSV encapsulation efficiency. Drug was loaded in both carriers as a molecular dispersion. Furthermore, the formulations had very low RSV release, which occurred due to the crystallinity degree of lipid matrix, in accordance with the DSC data. Moreover, RSV cytotoxicity against L-929 cells was not increased when loaded into nanocarriers. Interestingly, RSV-loaded formulation prepared with PEG-40 stearate resulted on greater tyrosinase inhibition than RSV solution and formulation containing glyceryl behenate, equivalent to 1.31 and 1.83 times higher, respectively, demonstrating that the incorporation of RSV into NLC allowed an enhanced tyrosinase inhibitory activity. Overall, the results obtained herein evidence potential for future in vivo evaluation of RSV-loaded NLCs.


Subject(s)
Drug Carriers/chemistry , Enzyme Inhibitors/administration & dosage , Fatty Acids/chemistry , Monophenol Monooxygenase/antagonists & inhibitors , Polyethylene Glycols/chemistry , Stilbenes/administration & dosage , Animals , Cell Line , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/toxicity , Nanostructures/chemistry , Particle Size , Resveratrol , Stilbenes/pharmacology , Stilbenes/toxicity
15.
Curr Protein Pept Sci ; 18(8): 850-863, 2017.
Article in English | MEDLINE | ID: mdl-28355998

ABSTRACT

Bioactive molecules such as peptides and proteins can optimize the repair of bone tissue; however, the results are often unpredictable when administered alone, owing to their short biological half-life and instability. Thus, the development of bioactive molecule-loaded drug delivery systems (DDS) to repair bone tissue has been the subject of intense research. DDS can optimize the repair of bone tissue owing to their physicochemical properties, which improve cellular interactions and enable the incorporation and prolonged release of bioactive molecules. These characteristics are fundamental to favor bone tissue homeostasis, since the biological activity of these factors depends on how accessible they are to the cell. Considering the importance of these DDS, this review aims to present relevant information on DDS when loaded with osteogenic growth peptide and bone morphogenetic protein. These are bioactive molecules that are capable of modulating the differentiation and proliferation of mesenchymal cells in bone tissue cells. Moreover, we will present different approaches using these peptide and protein-loaded DDS, such as synthetic membranes and scaffolds for bone regeneration, synthetic grafts, bone cements, liposomes, and micelles, which aim at improving the therapeutic effectiveness, and we will compare their advantages with commercial systems.


Subject(s)
Bone Morphogenetic Protein 2/pharmacology , Bone Regeneration/drug effects , Bone and Bones/drug effects , Drug Delivery Systems/methods , Histones/pharmacology , Intercellular Signaling Peptides and Proteins/pharmacology , Osteoblasts/drug effects , Animals , Biocompatible Materials/administration & dosage , Biocompatible Materials/metabolism , Bone Morphogenetic Protein 2/metabolism , Bone Regeneration/physiology , Bone Transplantation/methods , Bone and Bones/injuries , Bone and Bones/pathology , Cell Differentiation/drug effects , Histones/metabolism , Humans , Intercellular Signaling Peptides and Proteins/metabolism , Liposomes/administration & dosage , Liposomes/metabolism , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Micelles , Osteoblasts/cytology , Osteoblasts/metabolism , Osteogenesis/drug effects , Osteogenesis/physiology , Tissue Engineering/methods , Tissue Scaffolds
16.
J Biomed Nanotechnol ; 12(2): 241-60, 2016 Feb.
Article in English | MEDLINE | ID: mdl-27305759

ABSTRACT

Tuberculosis (TB) is an infectious and transmissible disease that is caused by Mycobacterium tuberculosis and primarily affects the lungs, although it can affect other organs and systems. The pulmonary presentation of TB, in addition to being more frequent, is also the most relevant to public health because it is primarily responsible for the transmission of the disease. The to their low World Health Organization (WHO) recommends a combined therapeutic regimen of several drugs, such as rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA) and ethambutol (ETB). These drugs have low plasma levels after oral administration, due to their low water solubility, poor permeability and ability to be rapidly metabolized by the liver and at high concentrations. Furthermore, they have short t1/2 (only 1-4 hours) indicating a short residence in the plasma and the need for multiple high doses, which can result in neurotoxicity and hepatotoxicity. Nanotechnology drug delivery systems have considerable potential for the treatment of TB. The systems can also be designed to allow for the sustained release of drugs from the matrix and drug delivery to a specific target. These properties of the systems enable the improvement of the bioavailability of drugs, can reduce the dosage and frequency of administration, and may solve the problem of non-adherence to prescribed therapy, which is a major obstacle to the control of TB. The purpose of this study was to systematically review nanotechnology-based drug delivery systems for the treatment of TB.


Subject(s)
Drug Delivery Systems/methods , Nanotechnology/methods , Tuberculosis/drug therapy , Drug Carriers/chemistry , Humans , Lipids/chemistry , Nanoparticles/chemistry
17.
Curr Top Med Chem ; 15(4): 287-97, 2015.
Article in English | MEDLINE | ID: mdl-25579344

ABSTRACT

Coordination compounds are substances in which a central metal atom is bonded to nonmetal atoms, or groups of atoms, called ligands. Examples include vitamin B12, hemoglobin, chlorophyll, dyes and pigments, as well as catalysts used in organic synthesis. Coordination compounds have received much attention in recent years. This interest was prompted by the discovery that several coordination compounds exhibit activity against bacteria, fungi and cancer. Some coordination compounds are not in clinical use, because of poor water solubility. Because they are unable to cross the lipid membranes of cells, bioavailability and efficacy are low. Some researchers have applied nanotechnology to coordination compounds, hoping to reduce the number of doses required and the severity of side effects, and also to improve biological activity. Nanotechnology can deliver active components in sufficient concentrations throughout treatment, guiding it to the desired location of action; conventional treatments do not meet these requirements. In this study we review some drug delivery systems based on nanotechnology, such as microemulsions (MEs), cyclodextrin (CD), polymeric nanoparticles (PN), solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), magnetic and gold nanoparticles (MNPs / AuNPs) and liquid crystalline systems (LC), and coordination compounds.


Subject(s)
Coordination Complexes/chemistry , Drug Carriers/chemistry , Nanoparticles/chemistry , Humans , Nanotechnology
18.
J Biomed Nanotechnol ; 10(9): 2218-43, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25992455

ABSTRACT

Women frequently develop disorders related to the vaginal area, including problems with the immune system, hygiene, genetic aspects and sexually transmitted diseases. Compared with other mucosal application sites, the vagina represents local effect as well as systemic drug delivery and is able to avoid the first-pass effect due to its large surface area, high blood supply and permeability to many active ingredients. It has been widely proposed that the use of drugs to treat vaginal disorders be combined with nanotechnology because nanosystems often potentiate the action of most active constituents, reducing the required dosage and side effects and improving the resulting activity in comparison with conventional treatments. Following the trend of using drug delivery systems based on nanotechology, many studies have encouraged the scientific community to turn to the development of new strategies for the vaginal administration of drugs. This study proposes to review the most common nanotechnology-based drug delivery systems that have been used to improve the effectiveness of active compounds administrated to treat vaginal disorders.


Subject(s)
Nanotechnology/methods , Pharmaceutical Preparations/administration & dosage , Administration, Intravaginal , Animals , Emulsions/chemistry , Female , Humans , Liposomes/chemistry , Nanoparticles/chemistry
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