Alternative routes for parenteral nucleic acid delivery and related hurdles: highlights in RNA delivery.

Introduction: Nucleic acid-based therapies are promising advancements in medicine. They offer unparalleled efficacy in treating previously untreatable diseases through precise gene manipulation techniques. However, the challenge of achieving targeted delivery to specific cells remains a significant obstacle.

Evaluation of Silybin Nanoparticles against Liver Damage in Murine Infection.

Silybin (SIB) is a hepatoprotective drug known for its poor oral bioavailability, attributed to its classification as a class IV drug with significant metabolism during the first-pass effect. This study explored the potential of solid lipid nanoparticles with (SLN-SIB-U) or without (SLN-SIB) ursodeoxycholic acid and polymeric nanoparticles (PN-SIB) as delivery systems for SIB. The efficacy of these nanosystems was assessed through in vitro studies using the GRX and Caco-2 cell lines for permeability and proliferation assays, respectively, as well as in vivo experiments employing a murine model of infection in BALB/c mice.

Modification of chicha gum: Antibacterial activity, ex vivo mucoadhesion, antioxidant activity and cellular viability.

The aim of the present work was to modify the exuded gum of Sterculia striata tree by an amination reaction. The viscosity and zero potential of the chicha gum varied as a function of pH. The modification was confirmed by X-ray diffraction (XRD), infrared spectroscopy (FTIR), size exclusion chromatography (SEC), zeta potential, thermogravimetric analysis (TG), and differential scanning calorimetry (DSC).

Lipoplexes and polyplexes as nucleic acids delivery nanosystems: The current state and future considerations.

Introduction: Designing safe and effective nucleic acid delivery nanosystems presents a challenge that requires a good understanding of various biological barriers, whose impact is frequently neglected during assessments. Hence, the development of nanosizing non-viral vectors would benefit from a more thorough physicochemical characterization to establish structure-activity relationships and increase the preclinical data relevance.

Areas Covered: This review focused on major barriers of lipoplexes and polyplexes by systemic delivery such as blood and immune cells and is aimed to serve as a prescreening tool for the fast and safe development of both non-viral vectors .

Sterculia striata gum as a potential oral delivery system for protein drugs.

Natural polysaccharides have been investigated as vehicles for oral insulin administration. Because of their non-toxic, renewable, low cost and readily available properties, gums find multiple applications in the pharmaceutical industry. This work aimed to develop a Sterculia striata gum-based formulation associated with additional biopolymers (dextran sulfate, chitosan, and albumin), a crosslinking agent (calcium chloride) and stabilizing agents (polyethylene glycol and poloxamer 188), to increase the oral bioavailability of proteins.

Sonication-assisted Layer-by-Layer self-assembly nanoparticles for resveratrol delivery.

This paper advances the development of a novel drug nanodelivery solution to the oral administration of resveratrol (RSV), a low soluble drug whose recognized therapeutic applications are circumscribed when administered in the free compound form. Layer-by-Layer (LbL) self-assembly is an emergent nanotechnology proposed to address this concern with means to afford control over key formulation parameters, which are able to ultimately promote an improved pharmacokinetics. LbL self-assembly consists in the sequential adsorption of oppositely charged polyelectrolytes upon a low soluble drug nanoparticle (NP) template, giving rise to onion-like multilayered nanoarchitectures.

Nanotechnology-based formulations for resveratrol delivery: Effects on resveratrol in vivo bioavailability and bioactivity.

Resveratrol (RES), also known as 3,5,4'-trihydroxystilbene, is a polyphenolic phytoalexin that has been widely researched in the past decade due to its recognized numerous biological activities. Despite the potential benefits of RES, its effective use is limited due to its poor solubility, photosensitivity and rapid metabolism, which strongly undermine RES bioavailability and bioactivity. Thereby, recently, nanotechnology appeared as a potential strategy to circumvent RES physicochemical and pharmacokinetics constrains.

Targeting Cancer Via Resveratrol-Loaded Nanoparticles Administration: Focusing on In Vivo Evidence.

Resveratrol (RSV) is a polyphenol endowed with potential therapeutic effects in chronic diseases, particularly in cancer, the second leading cause of death worldwide in the twenty-first century. The advent of nanotechnology application in the field of drug delivery allows to overcome the constrains associated with the conventional anticancer treatments, in particular chemotherapy, reducing its adverse side effects, off target risks and surpassing cancer multidrug chemoresistance. Moreover, the use of nanotechnology-based carriers in the delivery of plant-derived anticancer agents, such as RSV, has already demonstrated to surpass the poor water solubility, instability and reduced bioavailability associated with phytochemicals, improving their therapeutic activity, thus prompting pharmaceutical developments.

First-time oral administration of resveratrol-loaded layer-by-layer nanoparticles to rats - a pharmacokinetics study.

trans-Resveratrol (RSV) is a plant-derived polyphenol endowed with a broad spectrum of promising therapeutic activities. The applicability of RSV in vivo has, however, had limited success so far, largely due to its inefficient systemic delivery resulting from its low water solubility. Layer-by-Layer (LbL) nanotechnology constitutes an innovative formulation strategy to address this concern, and is based on the design of tunable onion-like multilayered nanoarchitectures on the surface of low solubility drug nanocores, such as RSV.

Subcutaneous delivery of biotherapeutics: challenges at the injection site.

Introduction: Biotherapeutics are primarily delivered subcutaneously due to better compliance and prolonged rate of absorption compared to other parenteral administration routes. Recent research has allowed for the development of biotherapeutic formulations for subcutaneous delivery that require a lower frequency of administration by increasing drug half-life. Formulations determine shelf-life stability as well as features and transient behaviors that influence stability once implanted in the subcutaneous space.

Solvent-free synthesis of acetylated cashew gum for oral delivery system of insulin.

Cashew gum (CG) is a biopolymer that presents a favorable chemical environment for structural modifications, which leads to more stable and resistant colloidal systems. The gum was subjected to an acetylation reaction using a fast, simple, solvent-free and low cost methodology. The derivative was characterized by infrared and NMR spectroscopy, elemental analysis, coefficient of solubility and zeta potential.

Subcutaneous delivery of monoclonal antibodies: How do we get there?

The convenience of subcutaneous (SC) administration and the increasing interest in monoclonal antibody (mAb)-based therapies for chronic diseases, hint their potential for SC delivery in a near future. In addition, there is a common interest among patients, clinicians and pharmaceutical industry in moving from intravenous to SC administration of mAbs due to benefits of improved patient compliance and reduced costs to the healthcare system. Despite the wide use of this route of administration in diseases like diabetes and rheumatoid arthritis, SC bioavailability of mAbs has been shown to be incomplete and variable in most preclinical and clinical studies.

Halloysite clay nanotubes for life sciences applications: From drug encapsulation to bioscaffold.

Natural forming clay halloysite is an emerging nanomaterial carrier for sustained drug delivery. These 50 nm diameter aluminosilicate tubes, with inner - alumina and outer - silica surface layers, can be loaded with 10-30 wt% of drug molecules, DNA and enzymes. The opposite charge of the inner and outer halloysite surface allow for selective drug adsorption inside or outside the clay nanotubes.

Unique Triphenylphosphonium Derivatives for Enhanced Mitochondrial Uptake and Photodynamic Therapy.

In this study, unique methyl-functionalized derivatives (T*PP) of the drug carrier triphenylphosphonium (TPP) that exhibit significant enhancement of the accumulation of both the cation and its conjugated cargo in cell mitochondria are designed. We show that the presence of methyl group(s) at key positions within the phenyl ring results in an increase in the hydrophobicity and solvent accessible surface area of T*PP. In particular, when the para position of the phenyl ring in T*PP is functionalized with a methyl group, the cation is most exposed to the surrounding environment, leading to a large decrease in water entropy and an increase in the level of van der Waals interaction with and partition into a nonpolar solvent.

Characterization of polymeric nanoparticles for intravenous delivery: Focus on stability.

The nano-bio interaction has been of increased focus in the past years but very limited results have been obtained for polymeric nanoparticles (NP). Not only is needed to broaden the results obtained with model NP towards other nano-materials used for clinical application but the colloidal stability of NP as a variable consequence of the formation of the protein corona has been significantly understated. The lack and heterogeneity of assays to study NP stability and represent the biological environment call for the standardization of assays to improve the representativeness and comparability of results.

Binding free energy calculations on E-selectin complexes with sLe oligosaccharide analogs.

Molecular dynamics simulations and binding free energy calculations were employed to examine the interaction between E-selectin and six structurally related oligosaccharides including the physiological ligand sialyl Lewis x. Molecular dynamics simulations revealed that sialyl Lewis x and its mimics share a common binding region and similar interactions with E-selectin involving the formation of hydrogen bonds with Glu80, Asn82, Asn83, Arg97, Asn105, Asp106, and Glu107 residues and electrostatic contacts with Ca and the positively charged Lys111 and Lys 113 residues. Regarding binding free energy calculations, the performance of the rigorous but computationally expensive pathway methods TI, BAR, and MBAR was compared to the less rigorous but faster end-point methods MM/PBSA and MM/GBSA aimed at identifying a suitable approach to deal with the very subtle binding free energy differences within the ligands under study.

Preparation methods and applications behind alginate-based particles.

Alginate-based particles have emerged as one of the most extensively searched drug delivery platforms due to their inherent properties, including good biocompatibility and biodegradability. Moreover, the low price, easy availability, natural origin, versatility and sol-gel transition properties, make alginate an ideal candidate to produce particles with different applications. Several techniques have been developed and optimized to prepare microparticles and nanoparticles in order to achieve more rational, coherent, efficient and cost-effective procedures.

Recent Advances in Nucleic Acid-Based Delivery: From Bench to Clinical Trials in Genetic Diseases.

Delivery of nucleic acids is the most promising therapy for many diseases that remain untreatable. Therefore, many research efforts have been put on finding a safe and efficient delivery system able to provide a sustained response. Viral vectors have proved to be the most efficient for delivery of nucleic acids and, thus, stand as the foremost vector used in current clinical trials.

Gums' based delivery systems: Review on cashew gum and its derivatives.

The development of delivery systems using natural polymers such as gums offers distinct advantages, such as, biocompatibility, biodegradability, and cost effectiveness. Cashew gum (CG) has rheological and mucoadhesive properties that can find many applications, among which the design of delivery systems for drugs and other actives such as larvicide compounds. In this review CG is characterized from its source through to the process of purification and chemical modification highlighting its physicochemical properties and discussing its potential either for micro and nanoparticulate delivery systems.

Improving the Biodesulfurization of Crude Oil and Derivatives: A QM/MM Investigation of the Catalytic Mechanism of NADH-FMN Oxidoreductase (DszD).

The development of biocatalytic desulfurization strategies of petroleum and its derivatives could result in more economic alternatives than the widely used chemical desulfurization. The organism Rhodococcus erythropolis IGTS8 has been shown to metabolize organic sulfur compounds through a mechanism known as 4S pathway, which involves four enzymes (DszA, DszB, DszC, and DszD) and has been explored in biodesulfurization. Here we have applied QM/MM methods to study the catalytic mechanism of the enzyme DszD, a NADH-FMN oxidoreductase that occupies a central place on the 4S pathway by catalyzing the formation of the FMNH2 that is used by the two monooxynases in the cycle: DszA and DszC.

Catalytic Mechanism of Retroviral Integrase for the Strand Transfer Reaction Explored by QM/MM Calculations.

Integrase (IN) is one of the three fundamental enzymes for the HIV life cycle. It irreversibly inserts the viral DNA into the host DNA, infecting the host cells. Although there are 37 compounds currently used in the HIV-1 antiretroviral therapy, only three have IN as a target.

Probing insulin bioactivity in oral nanoparticles produced by ultrasonication-assisted emulsification/internal gelation.

Alginate-dextran sulfate-based particles obtained by emulsification/internal gelation technology can be considered suitable carriers for oral insulin delivery. A rational study focused on the emulsification and particle recovery steps was developed in order to reduce particles to the nanosize range while keeping insulin bioactivity. There was a decrease in size when ultrasonication was used during emulsification, which was more pronounced when a cosurfactant was added.

Synthesis and Hydrolytic Studies on the Air-Stable [(4-CN-PhO)(E)P(μ-N(t)Bu)]2 (E = O, S, and Se) Cyclodiphosphazanes.

Reaction of 4-CN-PhOH with [ClP(μ-N(t)Bu)]2 (1) (2:1 ratio) in the presence of Et3N produced the functionalized cyclodiphosph(III/III)azane [(4-CN-PhO)P(μ-N(t)Bu)]2 (2). Oxidation of 2 produced cyclodiphosph(V/V)azanes [(4-CN-PhO)(E)P(μ-N(t)Bu)]2 [E = O (3), S (4), and Se (5)]. This is the first example of a series of cyclodiphosph(V/V)azane derivatives obtained from a single cyclophosph(III/III)azane precursor where all the accessible chalcogen oxidized products are air-stable over prolonged periods of time.