Drug Carriers

Non-invasive vaccine delivery is a top priority for public health agencies because conventional immunization practices are unsafe and associated with numerous limitations. Recently, the skin has emerged as a potential alternative route for non-invasive delivery of vaccine. Topical immunization (TI), introduction of antigen through topical application onto the intact skin, has many practical merits compared to injectable routes of administration. One of the possibilities for increasing the penetration of bioactives through the skin is the use of vesicular systems. Specially designed lipid vesicles are attracting intense attention and can be used for non-invasive antigen delivery. In the present study, elastic vesicle transfersomes, non-ionic surfactant vesicles (niosomes) and liposomes were used to study their relative potential in non-invasive delivery of tetanus toxoid (TT). Transfersomes, niosomes and liposomes were prepared and characterized for shape, size and entrapment efficiency. These vesicles were extruded through polycarbonate filter (50-nm pore size) to assess the elasticity of the vesicles. The immune stimulating activity of transfersomes, niosomes and liposomes were studied by measuring the serum anti-TT IgG titre following topical immunization. The immune response elicited by topical immunization was compared with that elicited by same dose of alum-adsorbed tetanus toxoid (AATT) given intramuscularly. The results indicate that optimal formulations of transfersomes, niosomes and liposomes could entrap 72.7 ± 3.4, 42.5 ± 2.4 and 41.3 ± 2.2% of antigen and their elasticity values were 124.4 ± 4.2, 29.3 ± 2.4 and 21.7 ± 1.9, respectively. In vivo study revealed that topically given TT containing transfersomes, after secondary immunization, could elicit immune response (anti-TT-IgG) that was equivalent to one that produced following intramuscularly alum-adsorbed TT-based immunization. In comparison to transfersomes, niosomes and liposomes elicited weaker immune response. Thus transfersomes hold promise for effective non-invasive topical delivery of antigen(s).

Novel microfluidic tools allow new ways to manufacture and test drug delivery systems. Organ-on-a-chip systems - microscale recapitulations of complex organ functions - promise to improve the drug development pipeline. This review highlights the importance of integrating microfluidic networks with 3D tissue engineered models to create organ-on-a-chip platforms, able to meet the demand of creating robust preclinical screening models. Specific examples are cited to demonstrate the use of these systems for studying the performance of drug delivery vectors and thereby reduce the discrepancies between their performance at preclinical and clinical trials. We also highlight the future directions that need to be pursued by the research community for these proof-of-concept studies to achieve the goal of accelerating clinical translation of drug delivery nanoparticles.

Novel microfluidic tools allow new ways to manufacture and test drug delivery systems. Organ-on-a-chip systems - microscale recapitulations of complex organ functions - promise to improve the drug development pipeline. This review highlights the importance of integrating microfluidic networks with 3D tissue engineered models to create organ-on-a-chip platforms, able to meet the demand of creating robust preclinical screening models. Specific examples are cited to demonstrate the use of these systems for studying the performance of drug delivery vectors and thereby reduce the discrepancies between their performance at preclinical and clinical trials. We also highlight the future directions that need to be pursued by the research community for these proof-of-concept studies to achieve the goal of accelerating clinical translation of drug delivery nanoparticles.

Dry powder formulations are often composed of fine drug particles and coarser carrier particles, typically alpha-lactose monohydrate. However, the performance of a powder formulation may be highly dependent on the lactose quality and source. This study investigated the characteristics of lactose that influence the drug-to-carrier interaction and the performance of lactose-based dry powder inhaler formulations. The selected lactoses differed in the preparation processes and the content of fine lactose particles. Efficiency testing was done using fluticasone propionate and terbutaline sulphate as model drugs. Inverse gas chromatography was used to determine the surface heterogeneity distribution of different energy sites of the lactose and to understand the mechanism by which the fine carrier particles can improve the performance of dry powder inhalers. To assess the adhesion of respirable-sized drug to carrier particles, a simple method was developed based on aspiration and consideri...

One major barrier limiting the transfection efficiency of polyplexes is poor endosomal release, especially when small particles are applied. In an approach to overcome this barrier, covalent attachment of the membrane-active peptide all-(L)-melittin to polyethylenimine (PEI) polyplexes was found to enhance gene transfer efficiency.

During the last decade, the application of nanotechnologies for anticancer drug delivery has been extensively explored, hoping to improve the efficacy and to reduce side effects of chemotherapy. The present review is dedicated to a certain kind of anticancer drug nanovectors developed to target tumors with the help of an external magnetic field. More particularly, this work treats anticancer drug nanoformulations based on superparamagnetic iron oxide nanoparticles coated with biocompatible polymers. The major purpose is to focus on the specific requirements and technological difficulties related to controlled delivery of antitumoral agents. We attempt to state the problem and its possible perspectives by considering the three major constituents of the magnetic therapeutic vectors: iron oxide nanoparticles, polymeric coating and anticancer drug.

The aim of this work was the evaluation of conductivity assessments for the monitoring and controlling the release study process of chlorhexidine and lidocaine hydrochloride from the ionic polyacrylic gel, applying different temperatures. According to performed measurements of release, the chlorhexidine, characterized by very low water solubility, is observed in the acceptor compartment in the amount of 2.0-3.0% and its level depends of the temperature. The amount of well soluble lidocaine hydrochloride released in parallel conditions was between 60 and 70%. Beyond, the assessments confirm the presence of a specific bond between the chlorhexidine imine groups and polyacrylic acid carboxylic groups. Presented method may be applied in the prediction of release rates, before actual release analysis, and may assure better evaluation of the systems.

In this paper, the parameters that are relevant to the drug redispersion from adhesive mixtures during inhalation are discussed and evaluated. The results obtained with air classifier technology give strong evidence for a dominating influence of carrier surface properties on the fraction of drug detached during inhalation at a low carrier payload (< or =1%, w/w), versus a dominating effect of carrier bulk properties at higher payloads. Furthermore, the results indicate that there is a fundamental difference between so-called active carrier sites and large surface discontinuities. The difference refers to the saturation concentrations, the rates of saturation and their effects on drug detachment during inhalation. The degree of saturation of the active sites appears to be proportional with the square root of the carrier surface payload (after 10 min mixing time in a Turbula mixer at 90 rpm). The storage volume of the discontinuities seems largely independent of the carrier diamete...

The two-part article aimed to investigate poloxamer 407-based microspheres as a novel platform for enhancing and controlling the delivery of atenolol across the oromucosal tissue. In the Part I of the work, atenolol-loaded poloxamers 407 microparticles were prepared by the solvent free spray congealing technology. This approach was feasible upon the high viscosity of the systems allowing for high loaded (20% w/w) non-aggregated microspheres. Several formulations were studied and the results demonstrated that the drug release patterns, solubility data, mucoadhesion to buccal tissue and gelling properties in saliva could be modified by adding different amount of an amphiphilic polymer-lipid excipient (Gelucire(®) 50/13) to poloxamer 407. Particularly, microspheres based only on poloxamer 407 exhibited very high solubility, mucoadhesive strength and gelling behaviour. To assess their potential as matrix for buccal application, the gelling property and the drug release from tablets obta...

Tripodal peptide analogues were designed on the basis of the phosphotyrosine binding pocket of the Src SH2 domain and assayed for their ability to bind to fluorescein-labeled phosphopeptides. Fluorescence polarization assays showed that a number of amphipathic linear peptide analogues (LPAs), such as LPA4, bind to fluorescein-labeled GpYEEI (F-GpYEEI). LPA4 was evaluated for potential application in cellular delivery of phosphopeptides. Fluorescence microimaging cellular uptake studies with fluorescein-attached LPA4 (F-LPA4) alone or with the mixture of LPA4 and F-GpYEEI in BT-20 cells showed dramatic increase of the fluorescence intensity in cytosol of cells, indicating that LPA4 can function as a delivery tool of F-GpYEEI across the cell membrane. Fluorescent flow cytometry studies showed the cellular uptake of F-LPA4 in an energy-independent pathway and confirmed the cellular uptake of F-GpYEEI in the presence of LPA4. These studies suggest that amphipathic tripodal peptide analo...

Skin penetrating peptides (SPPs) have garnered wide attention in recent years and emerged as a simple and effective noninvasive strategy for macromolecule delivery into the skin. Although SPPs have demonstrated their potential in enhancing skin delivery, they are still evolving as a new class of skin penetration enhancers. Detailed studies elucidating their mechanisms of action are still lacking. Using five SPPs (SPACE peptide, TD-1, polyarginine, a dermis-localizing peptide and a skin penetrating linear peptide) and a model hydrophobic macromolecule (Cyclosporine A, CsA), herein we provide a mechanistic understanding of SPPs. To evaluate the mechanism and safety of SPPs, their effects on skin lipids, proteins and keratinocyte cells were evaluated. Three SPPs (SPACE, Polyarginine and TD-1) significantly enhanced CsA penetration into the skin. SPPs did not alter the skin lipid barrier as measured by skin resistance, transepidermal water loss (TEWL) and Fourier transform infrared (FTI...

Enzymes, being remarkable catalysts, are capable of accepting a wide range of complex molecules as substrates and catalyze a variety of reactions with a high degree of chemo-, stereo- and regioselectivity in most of the reactions. Biocatalysis can be used in both simple and complex chemical transformations without the need for tedious protection and deprotection chemistry that is very common in traditional organic synthesis. This current review highlights the applicability of one class of biocatalysts viz.…

Niosomes has gained tremendous popularity as ultimate drug carrier. Lot of research work is being carried out on preparation of niosomes for ophthalmic use having no significant effect on vision and its sustained release pattern. Chloramphenicol niosomes were prepared using two different ratios of cholesterol, drug and surfactant, termed as EIN-1, EIN-2 by ether injection method and their entrapment efficiency, particle size. The in vitro drug release pattern was observed for ten hours. The EIN-2 showed 90% entrapment and released 81% of entrapped drug after 10 hours. Zeta potential & viscosity were determined and in-vivo comparison was made with Chloramphenicol eye drops where it exhibited Cmax of 15 μ g/ml. Stability studies were done to determine shelf life. MIC of selected strain of S. aureus was also determined. EIN 2 niosomal suspension was compared with Chloramphenicol eye drops in experimental conjunctivitis in albino rabbits. In-vitro studies are encouraging as niosomes released about 75% of total entrapped drug by EIN-1 and 81% of total entrapped drug by EIN 2. In vivo study shows that niosomes released the drug in eye in acceptable range and showed a sustained release pattern without affecting the vision. Niosomes were found ultimate ophthalmic drug carriers capable to release drug in sustained and determined pattern.

The goal of the current study was to explore the potential benefits of Acitretin (Act) nanovesicular gel as a prospective antipsoriatic topical delivery system counteracting the drug challenges in terms of its extremely low aqueous solubility, instability, skin irritation, and serious systemic adverse effects. Act-loaded niosomes were successfully developed, entirely characterized, and optimized. Further evaluation of the optimized formula was conducted regarding its stability and ex vivo cytotoxicity on different cell lines. The optimized niosomal vesicles were then incorporated in gel base matrix and investigated by sequential ex vivo (skin permeation and deposition) and in vivo (skin irritation and antipsoriatic activity using mouse tail model) experiments. The optimized Act-loaded niosomes (span 60:cholesterol molar ratio 1:1) were spherical in shape and exhibited the highest entrapment efficiency (90.32±3.80%) with appropriate nanosize and zeta potential of 369.73±45.45 nm and ...