Production of galactan phthalates derivatives extracted from Gracilaria birdie: Characterization, cytotoxic and antioxidant profile.

The present work explores the esterification reaction in the polysaccharide extracted from the seaweed Gracilaria birdiae and investigates its antioxidant potential. The reaction process was conducted with phthalic anhydride at different reaction times (10, 20 and 30 min), using a molar ratio of 1:2 (polymer: phthalic anhydride). Derivatives were characterized by FTIR, TGA, DSC and XRD. The biological properties of derivatives were investigated by assays of cytotoxicity and antioxidant activity (2,2-diphenyl-1-picrylhydroxyl - DPPH and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt - ABTS). The results obtained by FT-IR confirmed the chemical modification, there was a reduction related to the presence of carbonyl and hydroxyl groups when compared to the in nature polysaccharide spectrum. TGA analysis showed a change in the thermal behavior of the modified materials. X-ray diffraction, it was shown that the in nature polysaccharide appeared as an amorphous material, while the material obtained after the chemical modification process had increased crystallinity, due to the introduction of phthalate groups. For the biological assays, it was observed that the phthalate derivative was more selective than the unmodified material for the murine metastatic melanoma tumor cell line (B16F10), revealing a good antioxidant profile for DPPH and ABTS radicals.

Sorbitan Monolaurate-Containing Liposomes Enhance Skin Cancer Cell Cytotoxicity and in Association with Microneedling Increase the Skin Penetration of 5-Fluorouracil.

Squamous cell carcinoma (SCC) represents 20% of cases of non-melanoma skin cancer, and the most common treatment is the removal of the tumor, which can leave large scars. 5-Fluorouracil (5FU) is a drug used in the treatment of SCC, but it is highly hydrophilic, resulting in poor skin penetration in topical treatment. Some strategies can be used to increase the cutaneous penetration of the drug, such as the combination of liposomes containing penetration enhancers, for instance, surfactants, associated with the use of microneedling. Thus, the present work addresses the development of liposomes with penetration enhancers, such as sorbtitan monolaurate, span 20, for topical application of 5-FU and associated or not with the use of microneedling for skin delivery. Liposomes were developed using the lipid film hydration, resulting in particle size, polydispersity index, zeta potential, and 5-FU encapsulation efficiency of 88.08 nm, 0.169, -12.3 mV, and 50.20%, respectively. The presence of span 20 in liposomes potentiated the in vitro release of 5-FU. MTT assay was employed for cytotoxicity evaluation and the IC50 values were 0.62, 30.52, and 24.65 µM for liposomes with and without span 20 and 5-FU solution, respectively after 72-h treatment. Flow cytometry and confocal microscopy analysis evidenced high cell uptake for the formulations. In skin penetration studies, a higher concentration of 5-FU was observed in the epidermis + dermis, corresponding to 1997.71, 1842.20, and 2585.49 ng/cm2 in the passive penetration and 3214.07, 2342.84, and 5018.05 ng/cm2 after pretreatment with microneedles, for solution, liposome without and with span 20, respectively. Therefore, herein, we developed a nanoformulation for 5-FU delivery, with suitable physicochemical characteristics, potent skin cancer cytotoxicity, and cellular uptake. Span 20-based liposomes increased the skin penetration of 5-FU in association of microneedling. Altogether, the results shown herein evidenced the potential of the liposome containing span 20 for topical delivery of 5-FU.

Nanoemulsion of cashew gum and clove essential oil (Ocimum gratissimum Linn) potentiating antioxidant and antimicrobial activity.

In this study, nanoemulsions of essential oil from Ocimumgratissimum (Linn) (EO) were produced using low and high energy techniques using cashew gum (CG) as a co-surfactant. The main constituents of the EO were determined by Gas Chromatography coupled with Mass Spectrometry (GC-MS), and their presence in the EO and in the formulations verified by Fourier Transform Infrared Spectroscopy (FTIR) and UV-visible spectrophotometry was observed the encapsulation efficiency (EE%), with colloidal stability. Nuclear magnetic resonance (NMR) was used to study cashew gum. Dynamic light scattering analysis (DLS) determined the nanoemulsion Z means, polydispersity index and the Zeta potential value, nanoparticle tracking analysis (NTA) were determined. The nanostructured EO showed better antibacterial action against the pathogenic gastroenteritis species Staphylococcus aureus, Escherichia coli and Salmonella enterica when compared to free EO. Atomic Force Microscopy (AFM) was used for morphological analysis of the nanoparticle and study of the action of the nanoemulsion through images of the cellular morphology of S. enterica. The antioxidant activity was evaluated against the ABTS radical (2,2'-azino-bis diazonium salt (3-ethylbenzothiazoline-6-sulfonic acid)). The encapsulation of EO in a nanostructured system improved its antibacterial and antioxidant activity, the low energy synthesis showed greater storage stability, remaining stable for 37 days.

Synthesis of Eudragit® L100-coated chitosan-based nanoparticles for oral enoxaparin delivery.

Enoxaparin is an effective biological molecule for prevention and treatment of coagulation disorders. However, it is poorly absorbed in the gastrointestinal tract. In this study, we developed an Eudragit® L100 coated chitosan core shell nanoparticles for enoxaparin oral delivery (Eud/CS/Enox NPs) through a completely eco-friendly method without employing any high-energy homogenizer technique and any organic solvents. Spherical nanocarriers were successfully prepared with particle size lower than 300 nm, polydispersity index about 0.12 and zeta potential higher than +25 mV, entrapment efficiency greater than 95% and the in vitro release behavior confirms the good colloidal stability and the successful Eudragit® L100 coating process demonstrated by negligible cumulative enoxaparin release (<10%) when the particles are submitted to simulated gastric fluid conditions. Finally, we demonstrated that the core-shell structure of the particle influenced the drug release mechanism of the formulations, indicating the presence of the Eudragit® L100 on the surface of the particles. These results suggested that enteric-coating approach and drug delivery nanotechnology can be successfully explored as potential tools for oral delivery of enoxaparin.

Acetylated cashew gum and fucan for incorporation of lycopene rich extract from red guava (Psidium guajava L.) in nanostructured systems: Antioxidant and antitumor capacity.

Industrial application of lycopene is limited due to its chemical instability and low bioavailability. This study proposes the development of fucan-coated acetylated cashew gum nanoparticles (NFGa) and acetylated cashew gum nanoparticles (NGa) for incorporation of the lycopene-rich extract from red guava (LEG). Size, polydispersity, zeta potential, nanoparticles concentration, encapsulation efficiency, transmission electron microscopy (TEM) and atomic force microscopy (AFM) were used to characterize nanoparticles. The antioxidant activity was determinated and cell viability was evaluated in the human breast cancer cells (MCF-7) and human keratinocytes (HaCaT) by MTT assay. The toxic effect was evaluated by hemolysis test and by Galleria mellonella model. NFGa showed higher stability than NGa, having a size of 162.10 ± 3.21 nm, polydispersity of 0.348 ± 0.019, zeta potential -30.70 ± 0.53 mV, concentration of 6.4 × 109 nanoparticles/mL and 60% LEG encapsulation. Microscopic analysis revealed a spherical and smooth shape of NFGa. NFGa showed antioxidant capacity by ABTS method and ORAC assay. The NFGa presented significant cytotoxicity against MCF-7 from the lowest concentration tested (6.25-200 µg/mL) and did not affect the cell viability of the HaCaT. NFGa showed non-toxic effect in the in vitro and in vivo models. Therefore, NFGa may have a promising application in LEG stabilization for antioxidant and antitumor purposes.

Alendronate sodium-polymeric nanoparticles display low toxicity in gastric mucosal of rats and Ofcol II cells.

The use of bisphosphonates constitutes the gold-standard therapy for the control and treatment of bone diseases. However, its long-term use may lead to gastric problems, which limits the treatment. Thus, this study aimed to formulate a nanostructured system with biodegradable polymers for the controlled release of alendronate sodium. The nanoparticles were characterized, and its gastric toxicity was investigated in rats. The synthesis process proved to be effective for encapsulating alendronate sodium, exhibiting nanoparticles with an average size of 51.02 nm and 98.5% of alendronate sodium incorporation. The release tests demonstrated a controlled release of the drug in 420 min, while the morphological analyzes showed spherical shapes and no apparent roughness. The biological tests demonstrated that the alendronate sodium nanoformulation reversed the gastric lesions, maintaining the normal levels of malondialdehyde and myeloperoxidase. Also, the encapsulated alendronate sodium showed no toxicity in murine osteoblastic cells, even at high concentrations.

Anti-proliferative profile of Anacardium occidentale polysaccharide and characterization by AFM.

This paper explores the application of cashew gum (CG) as an in vitro antiproliferative, firstly by isolating and characterizing the gum using elemental analysis, gel-permeation chromatography, nuclear magnetic resonance (NMR) and atomic force microscopy (AFM). The molar mass of isolated CG was in the order of 103-104 g/mol, with small protein traces present. Polymer characterization by NMR identified key signals correlating to galactose, glucose, rhamnose and acid-related groups. Three distinct conformational stages were observed by AFM. The impact of CG on cell morphology and viability with both tumor and non-tumor cell lines was studied by AFM and 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay respectively. Antiproliferative activity was confirmed for HCT116 (colorectal carcinoma), B16F10 (melanoma) and HL60 (promyelocytic leukemia) cancer cell lines. A change in cell morphology was demonstrated as an increased surface roughness for HL60. Considering that a CG does not exhibit cytotoxicity to non-tumor lines, it can be seen that the CG shows selectivity for tumor cells and can be a promising biomaterial for future studies.

Development of amphotericin B-loaded propionate Sterculia striata polysaccharide nanocarrier.

This work was aimed at the production and characterization of a new nanocarrier based on a Sterculia striata polysaccharide (SSP) modified via acylation reaction with propionic anhydride. Nanocapsules of propionated SSP (PSSP) were produced via spontaneous nanoemulsification process and tested as a potential amphotericin B (AMB) nanocarrier. Stable nanoparticles with a very low polydispersity index (0.08-0.29) and high zeta potential (ζ -42.7 to -53.8 mV) were obtained. Particle size was dependent on the degree of substitution and ranged from 205 to 286 nm. A nanocapsule with a degree of substitution (DS) of 2.53 (NCP 2.53) was selected for encapsulation, biocompatibility, and antifungal evaluation against Candida albicans strains. A maximum of 98.3% AMB encapsulation was achieved. Encapsulated AMB was in its monomeric form and showed good biocompatibility and antifungal activity against four C. albicans strains. Data indicate that PSSP has potential as a nanocarrier system for AMB.

Nanocapsules of Sterculia striata acetylated polysaccharide as a potential monomeric amphotericin B delivery matrix.

Stable oil nanocapsules based on acetylated Sterculia striata polysaccharide (ASSP) were produced without the use of a surfactant, and derivatives of ASSP with four different degrees of substitution (DS) were synthesised. The data revealed that only derivatives with high DS were able to produce nanocapsules (NC), which exhibited monomodal size distribution profiles with a Z-average particle size, ζ-potential, and polydispersity index (PDI) that were dependent on ASSP DS and concentration. Nanocapsules were loaded with amphotericin B (AMB) with encapsulation efficiencies (EE%) that were dependent on drug and ASSP concentrations and DS. A maximum EE% value of 99.2% was achieved, and the loaded AMB was found to be in a monomeric form, even with a concentration one hundredfold higher than that usually observed for commercial AMB aqueous solutions. Loaded nanocapsules show an in vitro controlled release of AMB. As the monomeric AMB state decreased drug toxicity, ASSP nanocapsules loaded with AMB (NC1.68) have potential for use as a drug delivery system. AMB loaded NC 1.68 keeps its activity against 5 strains of Candida albicans tested.