384 research outputs found
The Release Kinetics of Melatonin from Innovative Dosage Forms: The Role of the Fractal Geometry of the “Vehicle”
Melatonin (N-acetyl-5-methoxytryptamine) is an antioxidant active pharmaceutical ingredient with numerous applications as medicine and nutraceutical. Melatonin, a hormone synthesized by the pineal gland, has a significant role in the regulation of the circadian biological clock. The aim of this chapter is to present the conventional solid and liquid forms (i.e., tables, capsules, suspensions, etc.) and the nanoformulations (i.e., liposomes, niosomes, polymeric nanoparticles, chitosomes, calcium alginate beads, etc.) of melatonin and to give special attention to its release kinetics from the pharmaceutical vehicle. These systems have been designed and developed as platforms for the delivery and release of melatonin. In all cases, the controlled release of melatonin is the main goal of its loading into drug delivery platforms. Fractal analysis is a mathematical tool to quantify nature and physical systems’ complexity. These systems have been characterized as fractal objects, due to their fractional dimensions. In this chapter, we are probing the interrelationship between the fractal dimension of pharmaceutical vehicle and the release profile of melatonin. Several examples will be given in order to understand in depth the reason of controlled-release profile of melatonin and its added value for the development of a new medicine and/or nutraceutical
Advanced nanocarriers for an antitumor peptide
In this work, tigapotide (PCK3145) was incorporated into novel nanocarriers based on polymeric, lipidic and dendrimeric components, in order to maximize the advantages of the drug delivery process and possibly its biological properties. PCK3145 was incorporated into lipidic nanocarriers composed of Eggphosphatidylcholine (EggPC) and dipalmytoylphosphatidylcholine (DPPC) (EggPC:PCK3145 and DPPC:PCK3145, 9:0.2 molar ratio), into cationic liposomes composed of EggPC:SA:PCK3145 and DPPC:SA:PCK3145 (9:1:0.2 molar ratio) into complexes with the block polyelectrolyte (quaternized poly[3,5bis(dimethylaminomethylene)hydroxystyrene]-b-poly(ethylene oxide) (QNPHOSEO) and finally into dendrimeric structures (i.e. PAMAM G4) . Light scattering techniques are used in order to examine the size, the size distribution and the z-potential of the nanocarriers in aqueous and biological media. Fluorescence spectroscopy was utilized in an attempt to extract information on the internal nanostructure and microenvironment of polyelectrolyte/PCK3145 aggregates. Therefore, these studies could be a rational roadmap for producing various effective nanocarriers in order to ameliorate the pharmacokinetic behavior and safety issues of antitumor and anticancer biomolecules
Complexation of cationic-neutral block polyelectrolyte with insulin and in vitro release studies
Insulin (INS) was incorporated into complexes with the block polyelectrolyte quaternized poly[3,5-bis(dimethylaminomethylene)hydroxystyrene]-b-poly(ethyleneoxide) (QNPHOSEO), which is a cationic-neutral block polyelectrolyte. Light scattering techniques are used in order to examine the size, the size distribution and the ζ-potential of the nanocarriers in aqueous and biological media, which are found to depend on the ratio of the components and the physicochemical parameters during and after complex preparation. Circular dichroism and infrared spectroscopy, employed to investigate the structure of the complexed INS, show no alteration of protein structure after complexation. In vitro release profiles of the entrapped protein are found to depend on the ratio of the components and the solution conditions used during preparation of the complexes
Insulin/Poly(ethylene glycol)-block-poly(L-lysine) Complexes: Physicochemical Properties and Protein Encapsulation
Insulin (INS) was encapsulated into complexes with poly(ethylene glycol)-block poly(L-lysine) (PEG-b-PLys), which is a polypeptide-based block copolymer (a neutral-cationic block polyelectrolyte). These macromolecules can encapsulate INS molecules in aqueous conditions via electrostatic interactions. Light scattering techniques are used in order to examine the complexation process of the hybrid nanoparticles in a gamut of buffers, as a function of protein concnetration. The physicochemical and structural characteristics of the complexes depend on the ionic strength of the aqueous medium, while the concentration of PEG-b-PLys was constant through the series of solutions. As INS concentration increased each polyelectrolyte chain interacts with an increasing number of INS molecules, the degree of charge neutralization becomes higher and the size distribution of the complexes decreased also, especially at the highest ionic strength. The size/structure of complexes diluted in biological medium indicated that the copolymer imparts stealth properties and colloidal and biological stability to the complexes, which could in turn affect the clearance properties in vivo. Therefore, these studies could be a rational roadmap for designing the optimum complexes/effective nanocarriers for proteins and peptides
A Novel Labda-7,13E-dien-15-ol-Producing Bifunctional Diterpene Synthase from Selaginella moellendorffii
Vascular plants invariably contain a class II diterpene cyclase (EC 5.5.1.x), as an ent-copalyl diphosphate synthase is required for gibberellin phytohormone biosynthesis. This has provided the basis for evolution of a functionally diverse enzymatic family.[1] These biocatalysts fold their substrate, the general diterpenoid precursor (E,E,E)-geranylgeranyl diphosphate (GGPP), to bring the terminal three carbon-carbon double bonds into proximity with each other, and then carry out bicyclization via a protonation-initiated carbocation cascade reaction. The resulting labda-15-en-8-yl+ diphosphate intermediate is most commonly quenched by deprotonation at an exocyclic methyl, as in the production of labdadienyl/copalyl diphosphate (Scheme 1). Alternatively, the bicyclized labda-15-en-8-yl+ diphosphate intermediate can be captured by water prior to deprotonation, to form hydroxylated compounds such as labda-15-en-8-ol diphosphate.[2] In addition, this intermediate can undergo subsequent rearrangement via 1,2-hydride and/or methyl shifts, starting with the hydrogen substituent on the neighboring endocyclic methine (C9).[3] However, terminating deprotonation at the neighboring endocyclic methylene (C7) has not previously been observed. Here we report that the lycophyte Selaginella moellendorffii contains a bifunctional diterpene synthase, SmCPSKSL1, which catalyzes just such a class II cyclization reaction. In particular, SmCPSKSL1 produces an endocyclic double bond isomer of copalyl diphosphate (CPP), as well as carries out subsequent replacement of the diphosphate by a hydroxyl group to form labda-7,13E-dien-15-ol. Although this is a known plant metabolite,[4] and a small family of bioactive derived natural products is known from a phylogenetically diverse group of plants,[4-5] its biosynthesis has not been previously investigated. Our results demonstrate that this diterpenoid can be generated by a single bifunctional diterpene synthase that directly generates the endocyclic double bond, as well as hydroxyl group
A study on the essential oil Ferulago campestris. How much does exstraction method influence the oil composition?
The essential oil of different parts of Ferulago campestris (Bess.) collected in Sicily has been
extracted by microwave-assisted hydrodistillation (MAHD) and by classic hydrodistillation
(HD). A comparative qualitative–quantitative study on the composition of the oils was
carried out. A total of 100 compounds were identified in the oils obtained by MAHD,
whereas 88 compounds characterized the HD oils. The most prominent components
were, in all different parts of F. campestris and in both extraction methods, 2,4,5-trimethylbenzaldehyde
and 2,4,6-trimethylbenzaldehyde isomers; the latter was not previously
found. The attempt to evaluate where the oil components are located in all parts of the
plant was carried out by means of a kinetic study. Then, electron microscopy observation
on the different parts before and after MAHD and HD was performed
Flavonoid Analyses and Antimicrobial Activity of Various Parts of Phaleria macrocarpa (Scheff.) Boerl Fruit
Phaleria macrocarpa (Scheff.) Boerl (Thymelaceae) is commonly known as ‘Crown of God’, ‘Mahkota Dewa’, and ‘Pau’. It originates from Papua Island, Indonesia and it grows in tropical areas. Empirically, it is potent in treating the hypertensive, diabetic, cancer and diuretic patients. It has a long history of ethnopharmacological usage, and the lack of information about its biological activities led us to investigate the possible biological activities by characterisation of flavonoids and antimicrobial activity of various part of P. macrocarpa against pathogenic bacteria and fungi. The results showed that kaempferol, myricetin, naringin, and rutin were the major flavonoids present in the pericarp while naringin and quercetin were found in the mesocarp and seed. Furthermore, the antibacterial activity of different parts of P. macrocarpa fruit showed a weak ability to moderate antibacterial activity against pathogenic tested bacteria (inhibition range: 0.93–2.17 cm) at concentration of 0.3 mg/disc. The anti fungi activity was only found in seed extract against Aspergillus niger (1.87 cm) at concentration of 0.3 mg/well. From the results obtained, P. macrocarpa fruit could be considered as a natural antimicrobial source due to the presence of flavonoid compounds
Docetaxel-loaded liposomes: The effect of lipid composition and purification on drug encapsulation and in vitro toxicity
Docetaxel (DTX)-loaded liposomes have been formulated to overcome DTX solubility issue, improve its efficacy and reduce its toxicity. This study investigated the effect of steric stabilisation, varying liposome composition, and lipid:drug molar ratio on drug loading and on the physicochemical properties of the DTX-loaded liposomes. Size exclusion chromatography (SEC) was used to remove free DTX from the liposomal formulation, and its impact on drug loading and in vitro cytotoxicity was also evaluated. Liposomes composed of fluid, unsaturated lipid (DOPC:Chol:DSPE-PEG2000) showed the highest DTX loading compared to rigid, saturated lipids (DPPC:Chol:DSPE-PEG2000 and DSPC:Chol:DSPE-PEG2000). The inclusion of PEG showed a minimum effect on DTX encapsulation. Decreasing lipid:drug molar ratio from 40:1 to 5:1 led to an improvement in the loading capacities of DOPC-based liposomes only. Up to 3.6-fold decrease in drug loading was observed after liposome purification, likely due to the loss of adsorbed and loosely entrapped DTX in the SEC column. Our in vitro toxicity results in PC3 monolayer showed that non-purified, DTX-loaded DOPC:Chol liposomes were initially (24h) more potent than the purified ones, due to the fast action of the surface- adsorbed drug. However, we hypothesize that over time (48 and 72h) the purified, DTX-loaded DOPC:Chol liposomes became more toxic due to high intracellular release of encapsulated DTX. Finally, our cytotoxicity results in PC3 spheroids showed the superior activity of DTX-loaded liposomes compared to free DTX, which could overcome the DTX poor tissue penetration, drug resistance, and improve its therapeutic efficacy following systemic administration
Chimeric Stimuli-Responsive Liposomes as Nanocarriers for the Delivery of the Anti-Glioma Agent TRAM-34
Nanocarriers are delivery platforms of drugs, peptides, nucleic acids and other therapeutic molecules that are indicated for severe human diseases. Gliomas are the most frequent type of brain tumor, with glioblastoma being the most common and malignant type. The current state of glioma treatment requires innovative approaches that will lead to efficient and safe therapies. Advanced nanosystems and stimuli-responsive materials are available and well-studied technologies that may contribute to this effort. The present study deals with the development of functional chimeric nanocarriers composed of a phospholipid and a diblock copolymer, for the incorporation, delivery and pH-responsive release of the antiglioma agent TRAM-34 inside glioblastoma cells. Nanocarrier analysis included light scattering, protein incubation and electron microscopy, and fluorescence anisotropy and thermal analysis techniques were also applied. Biological assays were carried out in order to evaluate the nanocarrier nanotoxicity in vitro and in vivo, as well as to evaluate antiglioma activity. The nanosystems were able to successfully manifest functional properties under pH conditions, and their biocompatibility and cellular internalization were also evident. The chimeric nanoplatforms presented herein have shown promise for biomedical applications so far and should be further studied in terms of their ability to deliver TRAM-34 and other therapeutic molecules to glioblastoma cells
Bioactive Constituents of Juniperus turbinata Gussone from La Maddalena Archipelago
A comprehensive phytochemical study of Juniperus turbinata (Cupressaceae) collected from La Maddalena Archipelago (Sardinia, Italy) is reported. Both the essential oil and the ethanolic extract obtained from the aerial parts were analyzed. The essential oil appears to belong to a new chemotype compared to other Mediterranean juniper accessions, as it was favored by geographic isolation of the isles. It showed a low content of monoterpene hydrocarbons and a-terpineol, entmanoyl oxide, 1,10-di-epi-cubenol as the major constituents. The ethanolic fraction contained mainly diterpenoids. Among these, 15-formyloxyimbricatolic acid (7) is a new natural product since it has hitherto been obtained only by synthetic route. The phenolic fraction contained biflavonoids: cupressuflavone (9), followed by minor amounts of amentoflavone (10) and hinokiflavone (11). The essential oil and six purified compounds (1 – 4, 8 and 9) were assessed for biological activities, namely antioxidant (assessed by DPPH·, ABTS·
+ and FRAP methods) and cytotoxic effects towards selected human tumor cell lines (MDA-MB 231, A375 and HCT116 cells). Compound 3 exhibited higher radical scavenging activity against ABTS·+ radical than the reference Trolox. Noteworthy, compound 8 showed powerful effects towards tumor cell lines, with IC50 values in the range of 0.060 – 0.201 lM, which make it a promising anticancer drug candidate
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