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Caffeic acid (CA), a hydrophobic polyphenol with various pharmacological activities, exhibits a low aqueous solubility and sensitivity to light. In order to improve its chemical properties and overcome the limits in its application, the compound was loaded in P123 micelles (MCs) prepared using two polymer concentrations (10 and 20% w/w, MC10 and MC20). The micelles were characterised in terms of the size distribution, zeta potential, drug encapsulation efficiency, rheology, and cumulative drug release. Micellar formulations exhibited sizes in the range of 11.70 and 17.70 nm and a good polydispersion, indicating the formation of relatively small-sized micelles, which is favourable for drug delivery applications. Additionally, the stability and antioxidant profiles of the free CA and the CA loaded in micelles were studied. The results obtained on the free CA showed the formation of photodegradation products endowed with higher DPPH scavenging activity with respect to the pure compound. Instead, it was found that the incorporation of CA into the micelles significantly increased its solubility and decreased the photodegradation rate. Overall, the results indicate the successful formation of P123 micelles loaded with CA, with promising characteristics such as a small size, good encapsulation efficiency, sustained release profile, and improved light stability. These findings suggest the potentiality of these micelles as a delivery system for CA, thus enhancing its bioavailability. [ABSTRACT FROM AUTHOR]

In the current study, a smart release system responsive to temperature was developed to improve the efficiency of tetracycline (TC) in antibacterial therapy. The nanovesicles designed consist of a non-ionic surfactant, SPAN60, cholesterol and a phase change material (PCM) as a thermoresponsive gating material. Niosomes were prepared using an increasing amount of PCM and characterized in terms of size, zeta potential, colloidal stability and thermoresponsive properties. The vesicles that developed were homogenous in size, had good biocompatibility and stability for up to 3 months and demonstrated thermoresponsive behavior. A low drug leakage was observed at 37 °C, while a rapid release occurred at 42 °C, due to the faster diffusion rate of the drug trough the melted PCM. This controllable drug release capacity allows us to avoid premature drug release, minimizing unwanted and toxic effects and ensuring a long retention time in the nanodevice so that it reaches the infected sites. In addition, TC-loaded niosomes were screened to investigate their antibacterial activity against various Gram-positive and Gram-negative bacteria by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. An interesting temperature-dependent antibacterial activity was observed against some bacterial strains: the niosomes activity against S. epidermis, for example, was improved by the temperature increase, as suggested by a reduction in MIC values from 112.81 to 14.10 μM observed at 37 and 42 °C, respectively. Taken together, the thermoresponsive platform developed allows us to use lower antibiotic amounts while ensuring therapeutic efficacy and, so, will advance the development of a novel antibacterial agent in clinical practice. [ABSTRACT FROM AUTHOR]

Background: This work proposes the development of new vesicular systems based on anesthetic compounds (lidocaine (LID) and capsaicin (CA)) and antimicrobial agents (amino acid-based surfactants from phenylalanine), with a focus on physicochemical characterization and the evaluation of antimicrobial and cytotoxic properties. Method: Phenylalanine surfactants were characterized via high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR). Different niosomal systems based on capsaicin, lidocaine, cationic phenylalanine surfactants, and dipalmitoyl phosphatidylcholine (DPPC) were characterized in terms of size, polydispersion index (PI), zeta potential, and encapsulation efficiency using dynamic light scattering (DLS), transmitted light microscopy (TEM), and small-angle X-ray scattering (SAXS). Furthermore, the interaction of the pure compounds used to prepare the niosomal formulations with DPPC monolayers was determined using a Langmuir balance. The antibacterial activity of the vesicular systems and their biocompatibility were evaluated, and molecular docking studies were carried out to obtain information about the mechanism by which these compounds interact with bacteria. Results: The stability and reduced size of the analyzed niosomal formulations demonstrate their potential in pharmaceutical applications. The nanosystems exhibit promising antimicrobial activity, marking a significant advancement in pharmaceutical delivery systems with dual therapeutic properties. The biocompatibility of some formulations underscores their viability. Conclusions: The proposed niosomal formulations could constitute an important advance in the pharmaceutical field, offering delivery systems for combined therapies thanks to the pharmacological properties of the individual components. [ABSTRACT FROM AUTHOR]

In this study, liposomes coated with novel multifunctional polymers were proposed as an innovative platform for tumor targeted drug delivery. Novel Folic acid–Cysteine-Thiolated chitosan (FTC) derivatives possessing active targeting ability and redox responsivity were synthesized, characterized, and employed to develop FTC-coated liposomes. Liposomes were characterized for size, surface charge and drug encapsulation efficiency before and after coating. The formation of a coating layer on liposomal surface was confirmed by the slight increase in particle size and by zeta-potential changes. FTC-coated liposomes showed a redox-dependent drug release profile: good stability at physiological conditions and rapid release of liposome-entrapped calcein in presence of glutathione. Moreover, the uptake and cytotoxic activity of doxorubicin-loaded FTC-coated liposomes was evaluated on murine B16-F10 and human SKMEL2 melanoma cancer cells. Results demonstrated enhanced uptake and antitumor efficacy of FTC-coated liposomes compared to control chitosan-coated liposomes in both cancer lines, which is attributed to higher cellular uptake via folate receptor-mediated endocytosis and to triggered drug release by the reductive microenvironment of tumor cells. The proposed novel liposomes show great potential as nanocarriers for targeted therapy of cancer. [ABSTRACT FROM AUTHOR]

Aqueous solution in the absence and presence of added lithium chloride, sodium chloride, and hydrochloric acid occurring when Bola C-16 operates in real systems is described. A reasonable agreement between experimental data and calculated intensities was obtained, taking into account amino group hydrolysis and assuming that the interaction potential is a sum of hard sphere and coulombic contributions.

Chemotherapy is a vital option for cancer treatment; however, its therapeutic outcomes are limited by dose-dependent toxicity and the occurrence of chemoresistance. siRNAs have emerged as an attractive therapeutic option enabling specific interference with target genes. Combination therapy using chemotherapeutic agents along with gene therapy could be a potential strategy for cancer management, which not only improves therapeutic efficacy but also decreases untoward effects from dose reduction. In this study, a cationic niosome containing plier-like cationic lipid B was used to convey siRNA against anti-apoptotic mRNA into MCF-7 and MDA-MB-231 cells. Mcl-1 silencing markedly decreased the viability of MCF-7 cells and triggered apoptosis. Moreover, computer modeling suggested that the combination of doxorubicin (Dox) and Mcl-1 siRNA exhibited a synergistic relationship and enabled a dose reduction of each agent at 1.71 and 3.91 folds, respectively, to reach a 90% inhibitory effect when compared to single-agent treatments. Synergistic antitumor activity was further verified in a 3D spheroid culture which revealed, in contrast to single-agent treatment, the combination markedly decreased spheroid volume over time. Together, the combination therapy between Mcl-1 silencing and Dox exhibits a synergistic effect that may be exploited for novel breast cancer treatment. [ABSTRACT FROM AUTHOR]

Simvastatin (SIM) is a HMG-CoA reductase inhibitor employed in the management of hyperlipidemia. However, its low bioavailability limits its clinical efficacy. The objective of this study was to overcome the poor bioavailability of SIM via the transdermal application of a SIM-loaded niosomal gel. Niosomes loaded with SIM were fabricated by means of the thin-film hydration method and optimized through a 33-factorial design utilizing Design Expert® software. The prepared niosomes were evaluated for entrapment efficiency (EE%), zeta potential, vesicle size, and cumulative percentage of drug release. The optimum niosomal formulation was loaded on the gel and evaluated for physical properties such as color, clarity, and homogeneity. It was also evaluated for spreadability, and the cumulative % drug release. The best niosomal gel formula was appraised for ex vivo permeation as well as pharmacokinetic study. The SIM-loaded niosomes showed EE% between 66.7–91.4%, vesicle size between 191.1–521.6 nm, and zeta potential ranged between −0.81–+35.6 mv. The cumulative percentage of drug released was ranged from 55% to 94% over 12 h. SIM-loaded niosomal gels were clear, homogenous, spreadable, and the pH values were within the range of physiological skin pH. Furthermore, about 73.5% of SIM was released within 24 h, whereas 409.5 µg/cm2 of SIM passed through the skin over 24 h in the ex vivo permeation study. The pharmacokinetic study revealed higher AUC0–∞ and Cmax with topical application of SIM-loaded niosomal gel compared to topical SIM gel or oral SIM suspension. The topical application of SIM-loaded niosomal gel ascertained the potential percutaneous delivery of SIM. [ABSTRACT FROM AUTHOR]

The clinical efficacy of methotrexate (MTX) is limited by its poor water solubility, its low bioavailability, and the development of resistance in cancer cells. Herein, we developed novel folate redox-responsive chitosan (FTC) nanoparticles for intracellular MTX delivery. l-Cysteine and folic acid molecules were selected to be covalently linked to chitosan in order to confer it redox responsiveness and active targeting of folate receptors (FRs). NPs based on these novel polymers could possess tumor specificity and a controlled drug release due to the overexpression of FRs and high concentration of reductive agents in the microenvironment of cancer cells. Nanoparticles (NPs) were prepared using an ionotropic gelation technique and characterized in terms of size, morphology, and loading capacity. In vitro drug release profiles exhibited a glutathione (GSH) dependence. In the normal physiological environment, NPs maintained good stability, whereas, in a reducing environment similar to tumor cells, the encapsulated MTX was promptly released. The anticancer activity of MTX-loaded FTC-NPs was also studied by incubating HeLa cells with formulations for various time and concentration intervals. A significant reduction in viability was observed in a dose- and time-dependent manner. In particular, FTC-NPs showed a better inhibition effect on HeLa cancer cell proliferation compared to non-target chitosan-based NPs used as control. The selective cellular uptake of FTC-NPs via FRs was evaluated and confirmed by fluorescence microscopy. Overall, the designed NPs provide an attractive strategy and potential platform for efficient intracellular anticancer drug delivery. [ABSTRACT FROM AUTHOR]