Vesicular Aggregates Research Articles

Supramolecular solvents based on hydrophobic natural deep eutectic solvents and primary amines for preconcentration and determination of enrofloxacin in milk

In this work, coacervation in primary amines solutions with hydrophobic natural deep eutectic solvents based on terpenoids and carboxylic acids was demonstrated for the first time. A liquid-phase microextraction approach was developed based on supramolecular solvent formation with primary amine acting as amphiphile and hydrophobic deep eutectic solvent making up mixed vesicles and serving as coacervation agent. Such supramolecular solvents could be used to separate wide range of substances from different aqueous media, such as food products, biological liquids and wastewaters. It is important that both hydrophobic and ionic interactions with supramolecular aggregates take place ensuring synergetic effect and better extraction ability, which is significant in separating relatively polar analytes. Different primary amines and deep eutectic solvents were investigated for liquid-phase microextraction of proof-of-concept amphoteric analyte (enrofloxacin, widely used veterinary fluoroquinolone antibiotic) and its determination by high-performance liquid chromatography with fluorescence detection using Shimadzu LC-20 Prominence chromatograph and RF-20A fluorescence detector. It was found that the supramolecular solvent based on 1-nonylamine, formed after addition of a deep eutectic solvent based on menthol and hexanoic acid (molar ratio of 1:1), provided maximum extraction recovery (85 %) and maximum enrichment factor (34). To characterize the extraction system, the composition of the phases was investigated, and cryo-transmission electron microscopy images were obtained. Vesicular aggregates were observed in the supramolecular solvent. The extraction mechanism was proposed in terms of formation of mixed aggregates to capture the analyte. Limit of detection was found to be 7 μg kg−1, while linear range of 20–250 μg kg−1 was established. Relative standard deviation values were lower than 7 %. Relative bias did not exceed 12 %.

The Reversible Transformation of a Vesicular Aggregate in Response to a pH Oscillation

The transformation of amphiphilic molecular assemblies in response to chemical oscillations is fundamental in biological systems. The reversible transformation of a vesicular aggregate (VA) in response to a pH oscillation is presented in this study. A VA composed of the cationic surfactant didodecyldimethylammonium bromide is transformed using a pH oscillation ranging between 3 and 7. When the VA attains a stable structure at extreme pH values, the transformation reaches the irreversible stage. However, the addition of a phosphate buffer to the VA suspension changes the pH oscillation pattern from being rectangular to triangular and decreases the oscillation amplitude, successfully achieving the reversible transformation of the VA. Maintaining the non-equilibrium (transient) structures throughout the transformation and not falling into the equilibrium state with a varying pH are essential for the reversible transformation. This may be common and essential for dynamics in biological cells.

Supramolecular Solvent-Based Vortex-Assisted Hollow Fibre Liquid-Phase Microextraction Technique Combined With High Performance Liquid Chromatography for the Determination of Estrogens in Milk Samples

A fast, simple, environmental friendly and strong sample clean-up ability method for the determination of three estrogens (17β-estradiol (17β-E2), estrone (E1), and diethylstilbestrol (DES)) in milk samples has been developed by using supramolecular solvent-based vortex-assisted hollow fibre liquid-phase microextraction (SS-VA-HF-LPME) and high performance liquid chromatography. Method is based on estrogens was extracted from aqueous samples into a supramolecular solvent which were made up of n-octanol and ionic liquid 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM] BF4) impregnated in the wall pores and also filled inside the porous polypropylene hollow fiber membrane followed by vortex-mixing. The supramolecular solvent has better compatibility with the polarity of target analytes and the driving forces for the extraction include hydrogen bonding, hydrophobic and π-cation interactions between the analytes and the vesicular aggregates, thereby leading to high recoveries. Vortex can provide mild and effective mixing of sample solution and increase the contact between analytes and boundary layers of the hollow fibre. Therefore the mass transfer rate was enhanced. The parameters that affect the recoveries were studied and optimized. HF of 4 cm length was used and the pH 4.0 was employed. The percentages of n-octanol and [BMIM]BF4 were 10% and 3%, respectively. The extraction equilibrium time was 4 min. The method provided good linearity (andgt;0.998), repeatability (RSD% = 1.24–4.36), low detection limit (0.10–0.22 ng mL−1), and high enrichment factor (330).

Structural characterization of lateral phase separation in polymer-lipid hybrid membranes.

Hierarchic self-assembly is the main mechanism used to create diverse structures using soft materials. This is a case for both synthetic materials and biomolecular systems, as exemplified by the non-covalent organization of lipids into membranes. In nature, lipids often assemble into single bilayers, but other nanostructures are encountered, such as bilayer stacks and tubular and vesicular aggregates. Synthetic block copolymers can be engineered to recapitulate many of the structures, forms, and functions of lipid systems. When block copolymers are amphiphilic, they can be inserted or co-assembled into hybrid membranes that exhibit synergistic structural, permeability, and mechanical properties. One example is the emergence of lateral phase separation akin to the raft formation in biomembranes. When higher-order structures, such as hybrid membranes, are formed, this lateral phase separation can be correlated across membranes in the stack. This chapter outlines a set of important methods, such as X-ray Scattering, Atomic Force Microscopy, and Cryo-Electron Microscopy, that are relevant to characterizing and evaluating lateral and correlated phase separation in hybrid membranes at the nano and mesoscales. Understanding the phase behavior of polymer-lipid hybrid materials could lead to innovative advancements in biomimetic membrane separation systems.

Detection of multiple metal ions exclusively at bilayer interface: Does the nature of the membranous aggregates affect the sensitivity?

A pyrenylated fluorogenic probe has been designed that can detect heavy metal pollutants exclusively at the bilayer interface. The compound, due to extensive self-aggregation, showed no interaction with metal ions in the bulk solution phase. However, effective, nanomolar level detection of multiple metal ions, such as Cu2+, Hg2+, and Ni2+, etc. was achieved exclusively in vesicular aggregates. The optical response towards metal ions, including selectivity and sensitivity, largely depends on the microenvironment around the probe molecules, governed by the nature of the bilayer membrane (polarity, order, interfacial hydration, etc). In zwitterionic membranes, like DPPC, Hg2+-induced fluorescence quenching was witnessed along with red-shifted emission maxima. On the contrary, turn-off responses along with blue-shifted in maxima were noted upon addition of both Cu2+ and Ni2+ ions in the anionic phospholipid vesicle, DPPA. Moreover, an improvement in sensitivity was witnessed when the probe was embedded into phospholipid vesicles with a fluid-like liquid crystalline phase. The larger mobility of the probe molecules on the bilayer membrane, resulting in ease of reorganization, might be the probable reason for this.

Design of Cationic Lipids with Acetal Linkers: Conformational preferences, Hydrolytic Stability and High Drug-loading Abilities.

Lipids are key constituents of numerous biomedical drug delivery technologies.Here, we present the design, synthesis, and biophysical characterizations of a library of cationic lipids containing an acetal residue in their linker region. These cationic acetal lipids (CALs) could be conveniently prepared through a trans-acetalization protocol from commercially available precursors. NMR studies highlighted the conformational rigidity at the acetal residue and the high hydrolytic stability of these CALs. Fluorescence anisotropy studies revealed that the CAL with pyridinium headgroup (CAL1) formed highly cohesive vesicular aggregates in water. These structural and self-assembly features of the CAL1 allowed up to 196% w/w loading of Curcumin (Cur) as a representative hydrophobic drug. A reconstitutable formulation of Cur was obtained as a result, which could deliver the drug inside mammalian cells with very high efficiency. The hemocompatibility and cytocompatibility of CAL1 was significantly enhanced by creating a coating of polydopamine (PDA) onto its vesicular assemblies to produce hybrid lipid-polymer nanocapsules. This work demonstrates rapid access to the useful synthetic lipid formulations with high potential in drug and gene delivery applications.

Supramolecular nanoassemblies of rim-differentiated pillar[5]arene-rod-coil macromolecules via host-guest interactions for the sensing of cis-trans isomers of 1,4-diol-2-butene

Over the past few years, pillar[n]arene molecules have gained attention as novel functional materials due to their unique properties, including their pore size structure and exceptional host-guest capabilities. Among them, rim-differentiated pillar[5]arene is particularly favored for its unique asymmetric structure. In this study, we present a self-assembled macrocyclic host molecule (H1) based on a rim-differentiated pillar[5]arene unit and five rod-coil side chains containing a hepta (ethylene glycol) mono-methyl ether modified biphenyl and phenyl groups, which was self-assemble into 2D columnar nanostructures in the bulk state. It self-organizes into a double-layer vesicular aggregate when in a CHCl3 solution. The host-guest interactions between the nanoobjects and the guest molecule (G) composed of tetraphenylethene and hexanenitrile groups resulted in the construction of ordered nanostructures with good luminescent properties, such as lamellar nanostructure in the bulk state and a single-layer nanosheet in CHCl3 solution. This demonstrated that the morphology of the H1 can be manipulated by forming host-guest complexes, and by adjusting the intermolecular interactions between the molecules. Moreover, in the presence of cis-trans isomers of 1,4-diol 2-butene, we successfully separated and visually detected the trans isomers through competitive host guest interactions. This result not only provides a general approach for separating the cis-trans isomers of 1,4-diol 2-butene through supramolecular chemistry, but also sets a precedent for future research in this field.

Cleaner technologies for asphalt mixtures combining reuse of residual aggregates, waste crumb rubber and warm mix asphalt additive

The reuse of waste materials and residual aggregates as well as the reduction of emissions has become vitally important for the environment, the economy and logistics of the asphalt paving industry. This study characterizes the performance and production properties of asphalt mixtures with waste crumb-rubber modifier from scrap tires, a warm mix asphalt surfactant additive and residual poor-quality volcanic aggregates as the single mineral component. The combination of these three cleaner technologies provides a promising solution to produce more sustainable materials by reusing two different types of waste and decreasing the manufacturing temperature at the same time. The compactability, stiffness modulus and fatigue performance characteristics were assessed in the laboratory for different low production temperatures and compared to conventional mixtures. The results indicate that these rubberized warm asphalt mixtures with residual vesicular and scoriaceous aggregates comply with the technical specifications for paving materials. The dynamic properties are maintained or even improved while reusing waste materials and allowing reductions of the manufacturing and compaction temperatures up to 20 °C, therefore, decreasing energy consumption and emissions.

Supramolecular Optimization of Sensory Function of a Hemicurcuminoid through Its Incorporation into Phospholipid and Polymeric Polydiacetylenic Vesicles: Experimental and Computational Insight.

This work presents the synthesis of a new representative of hemicurcuminoids with a nonyloxy substituent (HCur) as a fluorescent amphiphilic structural element of vesicular aggregates based on phosphatidylcholine (PC), phosphatidylserine (PS), and 10,12-pentacosadiynoic acid (PCDA). Both X-ray diffraction analysis of the single crystal and 1H NMR spectra of HCur in organic solvents indicate the predominance of the enol-tautomer of HCur. DFT calculations show the predominance of the enol tautomer HCur in supramolecular assemblies with PC, PS, and PCDA molecules. The results of the molecular modeling show that HCur molecules are surrounded by PC and PS with a rather weak exposure to water molecules, while an exposure of HCur molecules to water is enhanced under its supramolecular assembly with PCDA molecules. This is in good agreement with the higher loading of HCur into PC(PS) vesicles compared to PCDA vesicles converted into polydiacetylene (PDA) ones by photopolymerization. HCur molecules incorporated into HCur-PDA vesicles exhibit greater planarity distortion and hydration effect in comparison with HCur-PC(PS) ones. HCur-PDA is presented as a dual fluorescence-chromatic nanosensor responsive to a change in pH within 7.5-9.5, heavy metal ions and polylysine, and the concentration-dependent fluorescent response is more sensitive than the chromatic one. Thus, the fluorescent response of HCur-PDA allows for the distinguishing between Cd2+ and Pb2+ ions in the concentration range 0-0.01 mM, while the chromatic response allows for the selective sensing of Pb2+ over Cd2+ ions at their concentrations above 0.03 mM.

Mechanical performance under dynamic loading of rubberized asphalt mixtures with highly-porous vesicular aggregate

In volcanic regions, the use of certain abundant aggregates of scoriaceous nature with high porosity to manufacture bituminous paving mixtures is a major problem due to the excessive heterogeneity, absorption and limited strength of these aggregates. Consequently, the properties of the mixtures often do not meet technical specifications. The aim of this research is to study the improvement of the mechanical performance of asphalt mixtures with these residual volcanic aggregates by using binders modified with rubber from end-of-life tyres, since environmental and economic requirements make it necessary to reuse both types of waste. Laboratory studies determining the compactability, dynamic stiffness, fatigue resistance and elastic constants have made it possible to characterise the mechanical performance of these mixtures during production and in service, and to compare them with conventional mixtures. It was found that the use of tyre rubber modified bitumen makes compaction somewhat more difficult, but reduces the particle size degradation of the porous aggregates and improves the mixture performance and durability, showing higher stiffness moduli and increased resistance to fatigue.

Lidosomes: Innovative Vesicular Systems Prepared from Lidocaine Surfadrug.

Lidocaine is a local anaesthetic drug with an amphiphilic structure able to self-associate, under certain conditions, in molecular aggregates playing the role of both carrier and drug. The aim of this study was to determine the optimal conditions for obtaining vesicular carriers, called lidosomes. The new formulations were obtained using both lidocaine and lidocaine hydrochloride and different hydration medias (distilled water, acid, and basic aqueous solution). Lidosomes formulations were characterized in terms of size, ζ-potential, drug retained, stability formulation, and ex vivo permeation profile. Moreover, lidosomes were incorporated in two different gel structures: one based on carboxymethylcellulose and one based on pluronic F-127 to achieve suitable properties for a topical application. Results obtained showed that lidocaine showed a better performance to aggregate in vesicular carriers in respect to hydrochloride form. Consequently, only formulations comprised of lidocaine were studied in terms of skin permeation performance and as carriers of another model drug, capsaicin, for a potential combined therapy. Lidocaine, when in form of vesicular aggregates, acted as percutaneous permeation enhancer showing better permeation profiles with respect to drug solutions. Moreover, lidosomes created a significant drug depot into the skin from which the drug was available for a prolonged time, a suitable feature for a successful local therapy.

Analyzing Catalytic Co‐operativity and Membrane Parameters in a Substrate‐driven Vesicular Assembly Modified by Nucleotides

AbstractRationalizing changes in functional properties by an exogenous module in a synthetic nanoscale self‐organized system has broader significance in designing responsive biomimic materials having application in catalysis to therapeutics. Herein, we have developed a substrate‐driven nanoscale vesicular assembly of a metallosurfactant (with dipicolylamine co‐ordinated with zinc ion as headgroup) which simultaneously acts as a cooperative catalyst for the hydrolysis of the RNA‐model substrate, 2‐hydroxypropyl‐4‐nitrophenylphosphate (HPNPP). We have found out that both purine and pyrimidine‐based nucleoside monophosphates interact differently with the assembly, modulating the rate of catalytic cleavage. The different means of recognition of the nucleobases leads to alteration in membrane fluidity as well as surface charge of the vesicular aggregates whether the assembly is in catalytically active or inactive state. Then a systematic pattern for different nucleotides mediated vesicular nanoscale assembly composed of a catalytically‐active surfactant by statistically corelating alteration in dynamic membrane parameters (fluidity, surface charge) with its co‐operative phosphodiester hydrolyzing ability has been generated using principal component analysis as statistical tool. Overall, it showed a unique response pathway of a co‐operative functional assembly to different exogenous modules, and this perception of the deconvolution of collective property opens up an avenue for future development of advanced adaptive systems.

Controlling the two components modified on nanoparticles to construct nanomaterials.

Nanoparticle self-assembly technology has made great progress in the past 30 years. Many kinds of self-assembly strategies of modifiable nanoparticles have been developed and used to construct nano-aggregates by designing the shape, size and type of nanoparticles and controlling the components modified on nanoparticles. These strategies are widely used in many fields, such as medical diagnosis, biological detection, drug delivery, materials synthesis and sensors. The modified components can be DNA chains, polymer chains, proteins, and even organic molecules based on different molecular conformations and chemical properties. In recent years, the self-assembly of two-component modified nanoparticles has gradually attracted more attention. Nanoparticles modified with two components of different DNA strands can self-assemble to produce a variety of nano arrangement structures, such as BCC, FCC and other cubic crystals, which can be used in crystal materials. Two-component modification of hydrophilic and hydrophobic polymers can produce vesicular aggregates, which can be used for drug delivery. In this review, we summarize the latest experimental progress and theoretical simulation of self-assembly of two-component modified nanoparticles including different DNA chains, different polymer chains, DNA and polymer chains, proteins and polymer chains, and different organic molecules. Their self-assembly characteristics and application prospects were discussed. Compared with single-component modified nanoparticles, two-component nanoparticles have different tethered molecules or molecular chains, which can be multifunctional by regulating different modified components and types of nanoparticles and ultimately expand the scope of applications.

Development of Self-Cured Sustainable Concrete Using Local Water-Entrainment Aggregates of Vesicular Basalt

The environmental and economic concerns pertaining to the construction industry have necessitated the development of sustainable concrete. Durability and strength are the two primary properties which determine the sustainability of concrete. This study evaluated the performance of self-cured concrete produced from local vesicular basalt porous aggregates. The durability indicators, porosity, permeability and pore size of the hardened concrete, were obtained from the water sorptivity (water permeability under capillary action) test, the water permeability under pressure action test and the Brunauer–Emmett–Teller (BET) surface area test and strength was evaluated in terms of compressive strength of concrete. The concrete specimens were produced with 10% porous vesicular basalt aggregate in replacement of coarse aggregate. The concrete specimens were tested at 3, 7 and 28 days. The self-curing effect on concrete strength was evaluated against water, air and membrane cured specimens, at surface/volume ratio of 26.4/40 and w/c ratio of 0.35/0.5. A 20% decrease in sorptivity coefficient, 10% increase in solid surface area and about 10% increase in compressive strength of the self-cured concrete was observed over the conventionally cured concrete. The study concludes that the addition of water-entrainment aggregates to concrete reduces water permeability, results in a finer pore structure of concrete and increases the quality and durability of concrete.

Pharmacosomes as Drug Delivery System: An Overview

Pharmacosomes are the colloidal dispersions of drugs covalently bound to lipids and can exist, depending on the chemical structure, as ultrafine vesicular, micellar, or hexagonal aggregates. Because of the linking of a drug (pharmakon) to a carrier (soma), they are rightly termed "pharmacosomes."Pharmacosomes can be characterized as a neutral molecule with both positive and negative charges, water-loving and fat-loving characteristics, and in complex form, an ideal polyphenol-to-phospholipid ratio. Pharmacosomes are amphiphilic lipid vesicular systems that have demonstrated their ability to increase the bio-accessibility of poorly water-soluble and poorly lipophilic medicines. Drug pharmacosomes provide an effective method of delivering the drug directly to the infection site, which contributes to a lowering in drug toxicity without harmful effects, and also lowers the cost of therapy by improving the drug's bioavailability, particularly in the case of poorly soluble drugs. Pharmacosomes are appropriate to incorporate both hydrophilic and lipophilic drugs. Pharmacosomes have been designed for multiple anti-inflammatory medications that are non-steroidal, neurological, and antineoplasty.

Alpha helical surfactant-like peptides self-assemble into pH-dependent nanostructures.

A designed surfactant-like peptide is shown, using a combination of cryogenic-transmission electron microscopy and small-angle X-ray scattering, to have remarkable pH-dependent self-assembly properties. Peptide Arg3-Leu12 (R3L12) forms a network of peptide nanotubes at pH 9 and below. These are associated with α-helical conformation in a "cross-α" nanotube structure, in which peptide dimers lie perpendicular to the nanotube axis, with arginine coated inner and outer nanotube walls. In contrast, this peptide forms decorated vesicular aggregates at higher pH values, close to the pKa of the arginine residues. These structures are associated with a loss of α-helical order as detected through X-ray scattering, circular dichroism and FTIR spectroscopy, the latter technique also revealing a loss of ordering of leucine side chains. This suggests a proposed model for the decorated or patchy vesicular structures that comprises disordered peptide as the matrix of the membrane, with small domains of ordered peptide dimers forming the minority domains. We ascribe this to a lipid-raft like phase separation process, due to conformational disordering of the leucine hydrophobic chains. The observation of the self-assembly of a simple surfactant-like peptide into these types of nanostructure is remarkable, and peptide R3L12 shows unique pH-dependent morphological and conformational behaviour, with the potential for a range of future applications.

Monitoring the formation of a colloidal lipid gel at the nanoscale: vesicle aggregation driven by a temperature-induced mechanism.

Colloidal gels made of lipid vesicles at highly diluted conditions have been recently described. The structure and composition of this type of material could be especially relevant for studies that combine model lipid membranes with proteins, peptides, or enzymes to replicate biological conditions. Details about the nanoscale events that occur during the formation of such gels would motivate their future application. Thus, in this work we investigate the gelation mechanism, which consists of a lipid dispersion of vesicles going through a process that involves freezing and heating. The appropriate combination of techniques (transmission electron microscopy, differential scanning calorimetry and synchrotron small angle X-ray scattering) allowed in-depth analysis of the different events that give rise to the formation of the gel. Results showed how freezing damaged the lipid dispersion, causing a polydisperse suspension of membrane fragments and vesicles upon melting. Heating above the lipids' main phase transition temperature promoted the formation of elongated tubular structures. After cooling, these lipid tubes broke down into vesicles that formed branched aggregates across the aqueous phase, obtaining a material with gel characteristics. These mechanistic insights may also allow finding new ways to interact with lipid vesicles to form structured materials. Future works might complement the presented results with molecular dynamics or nuclear magnetic resonance experiments.

Anthracene based photo-tunable polymers with excimer emission

The aggregation properties of a diblock and a triblock copolymer in the aqueous phase has been investigated by photophysical and microscopy methods. Both copolymers possess photoresponsive hydrophobic poly(9-anthrylmethyl methacrylate) (PAN) block and hydrophilic polyethylene oxide (PEO) block whereas the triblock copolymer have an additional polystyrene (PSt) block at the middle. The amphiphilic copolymers, PAN-b-PEO and PAN-b-PSt-b-PEO, were synthesized by atom transfer radical polymerization (ATRP) method. Self-assembly of these individual copolymers in water leads to the formation of uniform spherical supramolecular assemblies. The morphology of the resultant spheres was disturbed by the illumination of the turbid aqueous solutions with 360 nm UV light accomplished by the photosolvolysis of the anthracenylmethyl ester. This irreversible photodissociation virtually transforms the amphiphilic diblock copolymer to a double hydrophilic block copolymer whereas the triblock copolymer because of its central PSt block was transformed into a bolaamphiphile. Complete micellar dissociation obtained in the case of diblock was not observed in the case of vesicular aggregates of the triblock copolymer. We also found that compared to the completely dissolved state, aggregation resulted in the pronounced excimer emission of the anthracene copolymers.

Emergence and Rearrangement of Dynamic Supramolecular Aggregates Visualized by Interferometric Scattering Microscopy.

Studying dynamic self-assembling systems in their native environment is essential for understanding the mechanisms of self-assembly and thereby exerting full control over these processes. Traditional ensemble-based analysis methods often struggle to reveal critical features of the self-assembly that occur at the single particle level. Here, we describe a label-free single-particle assay to visualize real-time self-assembly in aqueous solutions by interferometric scattering microscopy. We demonstrate how the assay can be applied to biphasic reactions yielding micellar or vesicular aggregates, detecting the onset of aggregate formation, quantifying the kinetics at the single particle level, and distinguishing sigmoidal and exponential growth of aggregate populations. Furthermore, we can follow the evolution in aggregate size in real time, visualizing the nucleation stages of the self-assembly processes and record phenomena such as incorporation of oily components into the micelle or vesicle lumen.

Development and Characterization of Levodopa Loaded Pharmacosomes for Brain Targeting via Intranasal Route: Pharmacodynamic Evaluation in Rats

Parkinson’s is the second most common progressive neurodegenerative disease and affects 1-2% people over the age 50. Levodopa is the drug of choice in the treatment of Parkinson’s disease and exhibits low oral bioavailability (30%) and very low brain uptake. In an attempt to improve brain uptake and to avoid degradation of levodopa in peripheral circulation, brain targeting of levodopa loaded pharmacosomes via nasal route has been investigated. Pharmacosomes are colloidal dispersions of drug covalently bound to lipids and may exist as ultrafine vesicular, micellar or hexagonal aggregates, depending on the chemical structure of the drug-lipid complex. Pharmacosomes loaded with levodopa were prepared by solvent evaporation method and the optimized formulation contained levodopa and egg lecithin in the ratio of 1:3. The mean globule size, PDI, zeta potential, drug content, entrapment efficiency and drug release of formulation (F5) were 123.2nm, 0.211, -29.1mV, 96%, 99.97% and 62.1% respectively. Permeation enhancer, chitosan was incorporated at 0.5% concentration to optimal formulation (F7). The mean globule size, PDI, zeta potential, drug content, entrapment efficiency and drug release of optimised formulation (F7) were 125.5nm, 0.115, +33.7mV, 96.5%, 99.98% and 91.2% respectively. Formation of covalent bond between levodopa and lecithin was confirmed by FTIR spectra showing peak at 1639.9cm-1. Ex-vivo permeation studies using Franz diffusion cell on porcine nasal mucosa showed flux of 96.61 μg/cm2/h and 302μg/cm2/h. The steady state flux of F5 and F7 formulations was significantly high (P Key words: Brain targeting, Levodopa, Nasal delivery, Parkinson’s disease, Pharmacosomes.