Development Of Novel Carriers Research Articles

Density functional theory analyses of an iron-doped nanocage for the adsorption of allopurinol drug towards the development of novel carriers

An iron-doped nanocage (FeC22) was assessed in this work based on density functional theory (DFT) calculations to work as a carrier of allopurinol (ALP) drug during its adsorption. The structural and electronic specifications were evaluated to analyze the formation of ALP@FeC22 conjugation yielding A1, A2, and A3 configurations with different featured properties. The existences of O…Fe, N…Fe, and H…C interactions were found for the conjugation formation in a physical non-covalent mode, in which the collaboration of N…Fe and H…C interactions yielded the strongest A3 conjugation with −49.31 kcal/mol strength. Interactions details also confirmed the formation of such strong conjugation. The electronic specifications based on the dominant frontier molecular orbitals showed measurable variations of features from the parental nanocage to the conjugation and also among the configurations. Finally, the FeC22 nanocage was proposed as a possible carrier of ALP by the formation of ALP@FeC22 conjugation for a smart drug delivery platform.

Review of Advances and Avenues in the Development of Novel Carriers for Bioactives and Biological Agents

Review of Advances and Avenues in the Development of Novel Carriers for Bioactives and Biological Agents

Dark cytotoxicity of submicrometer vaterite particles loaded with photosensitizer Fotoditazin and the vaterite-based core – shells structures

Photodynamic therapy (PDT) is based on the use of photosensitizers together with a light at the wavelength corresponding to its absorption maximum. Photosensitizers are able to generate reactive oxygen species under the visible or infrared light irradiation. They are broadly used for the treatment of cancer and infections due to their physical and chemical properties. Dose-dependent light induced cytotoxicity of photosensitizers shows the strong relation between its concentration in the treatment area and PDT efficiency. With this regard, the development of novel carriers for targeted delivery of photosensitizers is a very prospective research direction, as allows for the enhancement of the local drug concentration in the treatment area and the reduction of the incidental dark toxicity in healthy tissue associated with a classic PDT. Mesoporous vaterite particles are considered as a promising tool for biomedical application due to their biodegradability, high payload ability, as well as to the simplicity and cheapness of their fabrication. The efficiency of vaterite carrier application for a PDT delivery system design has been previously demonstrated. With this regard, the current study was aimed at the evaluation of dark cytotoxicity of the submicron vaterite particles and the vaterite-based core-shells, both loaded with Fotoditazin photosensitizer.

Cytotoxicity of cationic NHC copper(I) complexes coordinated to 2,2'-bis-pyridyl ligands

Cytotoxicity of cationic (NHC)Cu(I) complexes bearing 2,2′-dipyridylamine (dpa) type ligands has been evaluated toward 4 cancer cell lines, and compared to the one of neutral (NHC)Cu(I) complexes. The high cytotoxicity of these novel cationic (NHC)Cu(I) complexes, combined with the straightforward synthesis, and versatility of dpa type ligands may offer new prospects in cancer research, toward the development of novel carrier linked prodrugs.

Rutin–phospholipid complex in polymer matrix for long-term delivery of rutin via skin for the treatment of inflammatory diseases

The drug with poor oral bioavailability necessitates the development of novel carrier for efficient drug delivery. This paper reports the rutin–phospholipid complex in polymer matrix for sustained delivery of rutin via the skin for the treatment of acute and chronic inflammatory diseases. Rutin in phospholipid complex (RNPs) are better soluble and permeable than the free rutin. The RNPs-loaded polymeric matrix patch with moderate adhesiveness was developed for convenient means of long term drug application on the skin. The patch was analysed for physicochemical properties, ex vivo skin permeability and in vivo efficacy in rat paw oedema model. The skin targeting efficacy was analysed by CLSM study. Optimized formulation (F2) showed 31 ± 2.32% and 26.56 ± 5.52% skin permeation at 24 h across excised rat skin and human cadaver skin, respectively. The sustained anti-inflammatory effect of the patch formulation in rat paw oedema model confirmed its unique in vivo efficacy over the conventional diclofenac gel. The CLSM study confirmed the localization of RNPs in the dermis for sustained anti-inflammatory effect. Our results suggest that the developed patch has a potential for long term site specific delivery of rutin in arthritic patients.

Shape matters when engineering mesoporous silica-based nanomedicines.

Mesoporous silica nanomaterials have been successfully employed in the development of novel carriers for drug delivery. Numerous studies have been reported on engineering mesoporous silica-based carriers for drug loading, release, cellular uptake, and biocompatibility. A number of design parameters that govern the in vitro and in vivo performance of the carriers, including particle diameter, surface chemistry, and pore size, have been tuned to optimize nanomedicine efficacy. However, particle shape, which may generate a high impact on nanomedicine performance, has still not been thoroughly investigated. This is probably due to the limited availability of strategies and techniques to produce non-spherical mesoporous silica nanomaterials. Recent breakthroughs in controlling the particle shape of mesoporous silica nanomaterials have confirmed the important roles of shape on nanomedicine development. This review article introduces various fabrication methods for non-spherical mesoporous silica nanomaterials, including rod, ellipsoid, film, platelet/sheet, and cube, and the roles of particle shape in nanomedicine applications.

Topical delivery of clobetasol propionate loaded microemulsion based gel for effective treatment of vitiligo – Part II: Rheological characterization and in vivo assessment through dermatopharmacokinetic and pilot clinical studies

Vitiligo is a non contagious acquired pigmentation disorder with limited treatment possibilities. Clobetasol propionate (CP) is the drug-of-choice for vitiligo which suppresses the immune system by reducing immunoglobulin action and causes the restoration of melanocytes leading to repigmentation of skin. However, despite being effective, its low and variable bioavailability prompt for development of novel carrier that could effectively target CP to site of action without producing undesirable side-effects. Low solubility of CP in subsequent poor in vivo bioavailability was overcome by formulating microemulsion based gel of CP (MBC) which would enhance the percutaneous transport of CP into and across the skin barrier. Comprehensive characterization of MBC was carried out for viscosity, gel strength and rheological behavior. In vitro studies revealed much higher drug release, skin penetration and enhanced skin accumulation as compared to control (Cream of CP). In vitro and in vivo occlusion studies demonstrated similar occlusiveness for MBC and control. MBC exhibited 3.16 times higher stratum corneum CP levels compared to control. Visualization of cutaneous uptake in vivo using laser scanning microscopy confirmed targeting of CP to epidermis and dermis. Dermatopharmacokinetic studies of MBC showed enhanced drug deposition of CP in skin layers. MBC was assessed for in vivo efficacy by single blind randomized pilot clinical study. The efficacy was assessed by vitiligo area scoring index (VASI) method. After completion of trial, repigmentation of vitiligo patches in patients were evaluated and scored. MBC was superior in terms of faster repigmentation and efficacy when compared with control (p value<0.5). Hence, it was concluded that CP loaded MBC possess enhanced skin localization as well as therapeutic activity in vitiligo patients.

Size-Dependent Uptake of Particles by Pulmonary Antigen-Presenting Cell Populations and Trafficking to Regional Lymph Nodes

The respiratory tract is an attractive target organ for novel diagnostic and therapeutic applications with nano-sized carriers, but their immune effects and interactions with key resident antigen-presenting cells (APCs) such as dendritic cells (DCs) and alveolar macrophages (AMs) in different anatomical compartments remain poorly understood. Polystyrene particles ranging from 20 nm to 1,000 nm were instilled intranasally in BALB/c mice, and their interactions with APC populations in airways, lung parenchyma, and lung-draining lymph nodes (LDLNs) were examined after 2 and 24 hours by flow cytometry and confocal microscopy. In the main conducting airways and lung parenchyma, DC subpopulations preferentially captured 20-nm particles, compared with 1,000-nm particles that were transported to the LDLNs by migratory CD11blow DCs and that were observed in close proximity to CD3⁺ T cells. Generally, the uptake of particles increased the expression of CD40 and CD86 in all DC populations, independent of particle size, whereas 20-nm particles induced enhanced antigen presentation to CD4⁺ T cells in LDLNs in vivo. Despite measurable uptake by DCs, the majority of particles were taken up by AMs, irrespective of size. Confocal microscopy and FACS analysis showed few particles in the main conducting airways, but a homogeneous distribution of all particle sizes was evident in the lung parenchyma, mostly confined to AMs. Particulate size as a key parameter determining uptake and trafficking therefore determines the fate of inhaled particulates, and this may have important consequences in the development of novel carriers for pulmonary diagnostic or therapeutic applications.

In vitro reconstitution of SV40 particles that are composed of VP1/2/3 capsid proteins and nucleosomal DNA and direct efficient gene transfer

SV40 is comprised of the viral minichromosome and the capsid proteins VP1, VP2, and VP3. Complete reconstitution of SV40 virions in vitro remains a challenge. Here we describe in vitro reconstitution of SV40 particles that contain ~ 5-kb circular nucleosomal DNA with hyperacetylated histones and are encapsidated in a coat composed of VP1, VP2, and VP3, closely mimicking the characteristics of authentic SV40 virions. When inoculated into mammalian cells, VP1/2/3 particles containing nucleosomal DNA carrying a reporter gene yielded a significantly higher level of gene expression than VP1-only particles containing the corresponding naked DNA. The elevated gene expression resulted mainly from enhanced association of the particles with the cell surface and from facilitation of subsequent uptake into cells. Thus, the in vitro reconstitution system reported here should be useful for the elucidation of Polyomaviridae assembly mechanisms and for the development of novel carriers for gene delivery.

Safer Than Safe: Lipid Nanoparticulate Encapsulation of Tacrolimus with Enhanced Targeting and Improved Safety for Atopic Dermatitis

Atopic dermatitis (AD) is a skin disorder having significant impact worldwide, characterized by itchy, erythematous and intensely pruritic rash with periods of remission. Tacrolimus is the drug-of-choice in treatment of many immune mediated dermatoses including AD. Despite being effective, most common adverse events of tacrolimus are burning sensation and pruritus at the application site prompting for development of novel carrier that could effectively target tacrolimus to site-of-action without producing undesirable toxic-effects. Tacrolimus loaded lipid nanoparticles (T-LN) were developed and evaluated comparatively for enhanced targeting potential to site of action and improved safety with commercially available ointment product, Protopic as reference. T-LN was successfully developed by high pressure homogenization technique. Significantly higher drug release and skin permeating properties were observed for T-LN as compared to reference. T-LN suppressed inflammatory response in vivo by 3.5 times more efficiently than reference, demonstrating its improved efficacy. Entrapment of tacrolimus in lipid nanoparticles avoided direct contact of drug with skin; alleviating drug related local side effects.

Targeting tacrolimus to deeper layers of skin with improved safety for treatment of atopic dermatitis

Atopic dermatitis (AD) is chronically relapsing eczematous skin disorder having significant impact worldwide. Tacrolimus is the drug-of-choice which inhibits T-cell activation resulting in suppression of inflammation. However, despite being effective, most common adverse events of tacrolimus are low-and-variable bioavailability, burning sensation and pruritus at application site, which prompt for development of novel carrier that could effectively target tacrolimus to site-of-action without producing undesirable side-effects. Tacrolimus-loaded lipid-nanoparticles (T-LN) were prepared and optimized. DSC and FT-IR have been employed to study drug-excipient incompatibility and encapsulation of drug in lipid which was further confirmed by 1H NMR. In vitro studies revealed much higher drug release, skin penetration and enhanced skin accumulation as compared to reference Protopic ®. In vitro and in vivo occlusion studies demonstrated similar occlusiveness for T-LN and reference however; T-LN showed significantly higher drug levels penetrating into deeper skin layers where dendritic cells responsible for immunopathogenesis of AD mainly reside. In-vivo skin retention demonstrated 3.36, 30.81 and 28.68-times higher stratum corneum, epidermal and dermal levels respectively compared to reference. Visualization of cutaneous uptake in-vivo using CLSM confirmed targeting to deeper skin layers and Draize test showed no skin irritation with PII 0.00. Thus T-LN displayed superior performance, effective skin targeting and improved safety as compared to reference.

Flow and adhesion of drug carriers in blood vessels depend on their shape: A study using model synthetic microvascular networks

Development of novel carriers and optimization of their design parameters has led to significant advances in the field of targeted drug delivery. Since carrier shape has recently been recognized as an important design parameter for drug delivery, we sought to investigate how carrier shape influences their flow in the vasculature and their ability to target the diseased site. Idealized synthetic microvascular networks (SMNs) were used for this purpose since they closely mimic key physical aspects of real vasculature and at the same time offer practical advantages in terms of ease of use and direct observation of particle flow. The attachment propensities of surface functionalized spheres, elliptical/circular disks and rods with dimensions ranging from 1 μm to 20 μm were compared by flowing them through bifurcating SMNs. Particles of different geometries exhibited remarkably different adhesion propensities. Moreover, introduction of a bifurcation as opposed to the commonly used linear channel resulted in significantly different flow and adhesion behaviors, which may have important implications in correlating these results to in vivo behavior. This study provides valuable information for design of carriers for targeted drug delivery.

Drug delivery systems: Advanced technologies potentially applicable in personalized treatments.

Advanced drug delivery systems (DDS) present indubitable benefits for drug administration. Over the past three decades, new approaches have been suggested for the development of novel carriers for drug delivery. In this review, we describe general concepts and emerging research in this field based on multidisciplinary approaches aimed at creating personalized treatment for a broad range of highly prevalent diseases (e.g., cancer and diabetes). This review is composed of two parts. The first part provides an overview on currently available drug delivery technologies including a brief history on the development of these systems and some of the research strategies applied. The second part provides information about the most advanced drug delivery devices using stimuli-responsive polymers. Their synthesis using controlled-living radical polymerization strategy is described. In a near future it is predictable the appearance of new effective tailor-made DDS, resulting from knowledge of different interdisciplinary sciences, in a perspective of creating personalized medical solutions.

Development of novel carrier using natural zeolite and continuous ethanol fermentation with immobilized Saccharomyces cerevisiae in a bioreactor

A natural zeolite, easily vitrified and blown at 1300 °C with a high porosity and diam. of 5–100 μm, was used to immobilize Saccharomyces cerevisiae at 3.6 × 108 cells ml−1 carrier. When the abilities of natural zeolite carrier were compared with glass beads, the capacity for immobilization and alcohol fermentation activity were, respectively, 2′-fold higher and 1.2-fold higher than that of glass beads. Continuous alcohol fermentation was stable for over 21 d without breakage of the carrier.