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Amorphous solid dispersion (ASD) has been widely used to enhance the oral bioavailability of water-insoluble drugs for oral delivery because of its advantages of enhancing solubility and dissolution rate. However, the problems related to drug recrystallization after drug dissolution in media or body fluid have constrained its application. Recently, a self-nanomicellizing solid dispersion (SNMSD) has been developed by incorporating self-micellizing polymers as carriers to settle the problems, markedly improving the ability of supersaturation maintenance and enhancing the oral bioavailability of drug. Spontaneous formation and stability of the self-nanomicelle (SNM) have been proved to be the key to supersaturation maintenance of SNMSD system. This offers a novel research direction for maintaining supersaturation and enhancing the bioavailability of ASDs. To delve into the advantages of SNMSDs, we provide a concise review introducing the formation mechanism, characterization methods and stability of SNMs, emphasizing the advantages of SNMSDs for oral drug delivery facilitated by SNM formation, and discussing relevant research prospects.

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In this present formulation study, vinpocetine-loaded nano-spray-dried polymeric micelles were developed via nano-spray-drying. Three different mucoadhesive excipients were applied in the studies, namely chitosan, hyaluronic acid and hydroxypropyl methylcellulose. In all cases, the formulations had a proper particle size and drug content after drying with spherical morphology and amorphous structure. After rapid dissolution in water, the polymeric micelles had a particle size around 100-130 nm, in monodisperse size distribution. The high encapsulation efficiency (>80%) and high solubilization (approx. 300-fold increase in thermodynamic solubility) contributed to rapid drug release (>80% in the first 15 min) and fast passive diffusion at simulated nasal conditions. The formulated prototype preparations fulfilled the demands of a low-viscosity, moderately mucoadhesive nasal drug delivery system, which may be capable of increasing the overall bioavailability of drugs administered via the auspicious nasal drug delivery route.

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Local treatment of bladder cancer faces several limitations such as short residence time or low permeation through urothelium tissue. The aim of this work was to develop patient-friendly mucoadhesive gel formulations combining gemcitabine and the enzyme papain for improved intravesical chemotherapy delivery. Hydrogels based on two different polysaccharides, gellan gum and sodium carboxymethylcellulose (CMC), were prepared with either native papain or papain nanoparticles (nanopapain) to explore for the first time their use as permeability enhancers through bladder tissue. Gel formulations were characterized regarding enzyme stability, rheological behavior, retention on bladder tissue and bioadhesion, drug release properties, permeation capacity, and biocompatibility. After 90 days of storage, the enzyme loaded in the CMC gels retained up to 83.5 ± 4.9 % of its activity in the absence of the drug, and up to 78.1 ± 5.3 with gemcitabine. The gels were mucoadhesive and the enzyme papain showed mucolytic action, which resulted in resistance against washing off from the urothelium and enhanced permeability of gemcitabine in the ex vivo tissue diffusion tests. Native papain shortened lag-time tissue penetration to 0.6 h and enhanced 2-fold drug permeability All formulations demonstrated pseudoplastic behavior and no irritability. Overall, the developed formulations have potential as an upgraded alternative to intravesical therapy for bladder cancer treatment.

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Multiple daily injections via subcutaneous route are the primary modes of insulin delivery for patients with Diabetes Mellitus. While this process is invasive, painful and may cause patients to develop lipohypertrophy at injection site, the perception of fear surrounding this process causes patients to delay in initiation and remain persistent with insulin therapy over time. Moreover, poor glycemic control may often lead to acute complications, such as severe hypoglycemia and nocturnal hypoglycemia, especially in older patients with diabetes. To address the imperative need for a patient-convenient non-invasive insulin therapy, an insulin-loaded arginine-coated self-emulsifying nanoglobule system (INS-LANano) was developed for nasal delivery of insulin with a biodegradable cationic surfactant-Lauroyl Ethyl Arginate (LAE). Incorporation of LAE resulted in formation of positively charged nanoglobules with L-arginine oriented on the surface. LANano enabled binding of insulin molecules on the surface of nanoglobules via an electrostatic interaction between negatively charged α-helix and LAE molecules at physiological pH. INS-LANano showed a hydrodynamic diameter of 23.38 nm with a surface charge of +0.118 mV. The binding efficiency of insulin on LANano globules was confirmed by zeta potential, circular dichroism (CD) spectroscopy and centrifugal ultrafiltration studies. The attachment of insulin with permeation-enhancing nanoglobules demonstrated significantly higher in vitro permeability of insulin of 15.2% compared to insulin solution across human airway epithelial cell (Calu-3) monolayer. Upon intranasal administration of INS-LANano to diabetic rats at 2 IU/kg insulin dose, a rapid absorption of insulin with significantly higher Cmax of 14.3 mU/L and relative bioavailability (BA) of 23.3% was observed. Therefore, the INS-LANano formulation significant translational potential for intranasal delivery of insulin.

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In our present series of experiments, we investigated the nasal applicability of the previously developed Soluplus® - meloxicam polymeric micelle formulation. Utilizing the nasal drug investigations, moderately high mucoadhesion was experienced in nasal conditions which alongside the appropriate physicochemical properties in liquid state, contributed to rapid drug absorption through human RPMI 2650 cell line. Ex vivo studies also confirmed that higher nasal mucosal permeation could be expected with the polymeric micelle nanoformulation compared to a regular MEL suspension. Also, the nanoformulation met the requirements to provide rapid drug permeation in less 1 h of our measurement. The non-toxic, non-cell barrier damaging formulation also proved to provide a successful passive transport across excides human nasal mucosa. Based on our in vivo investigations, it can be concluded that the polymeric micelle formulation provides higher meloxicam transport to the central nervous system followed by a slow and long-lasting elimination process compared to prior results where physical particle size reduction methods were applied. With these results, a promising solution and nanocarrier is proposed for the successful transport of non-steroidal anti-inflammatory drugs with acidic character to the brain.

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As a promising strategy, amorphous solid dispersion has been extensively employed in improving the oral bioavailability of insoluble drugs. Despite the numerous advantages, the problems associated with supersaturation stability limit its further application. Recently, the formation and stability of the liquid-liquid phase separation drug aggregate (LLPS-DA) have been found to be vital for supersaturation maintenance. An in-depth review of LLPS-DA was required to further explore the supersaturation maintenance mechanism in vivo. Hence, this study aimed to present a short review to introduce the LLPS-DA, highlight the in vivo advantages for oral administration, and discuss the prospects to help understand the in vivo behavior of LLPS-DA.

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Through liquid-liquid phase separation (LLPS), it is possible to generate drug-rich nanoparticles during the dissolution of conventional amorphous solid dispersions (ASDs). These self-generated nanoparticles may improve the oral absorption of poorly water-soluble drugs by enhancing the drug's apparent solubility and effective membrane permeability. However, due to the high concentration threshold required for LLPS, conventional ASDs that can consistently generate drug-rich nanoparticles during dissolution are rare. More importantly, the quality of these meta-stable drug-rich nanoparticles is hard to control during dissolution, leading to inconsistency in formulation performances. This work has described a continuous twin-screw extrusion process capable of producing nanosized ASD (NASD) formulations that can offer better solubility and permeability enhancements over conventional ASD formulations. Two polymeric carriers, polyvinylpyrrolidone-co-vinyl acetate (PVPVA) and hydroxypropyl methylcellulose acetate succinate (HPMCAS), with a model hydrophobic drug celecoxib (BCS II), were formulated into both ASD and NASD formulations. Compared to the conventional ASD formulation, the prefabricated NASD (sizes ranging between 40 and 200 nm) embedded within a polyol matrix can be rapidly dispersed into a nanoparticle suspension in the presence of aqueous media. The resulting NASDs achieved drug loadings up to 80 % w/w and a maximum of 98 % encapsulation efficiency. Because of the TSE platform's high drug-loading capacity and high scalability, the developed method may be useful for continuously producing personalized nanomedicines.

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In the context of increased interest in permeability enhancement technologies to achieve mucosal delivery of drugs and biologics, we report our study on effects of the amphiphilic surfactant at cell membrane and cell population levels. Our results show that modulation in membrane order and fluidity initially occurs on insertion of individual surfactant molecules into the outer leaflet of membrane lipid bilayer; a process occurring at concentrations below surfactant's critical micellar concentration. The surfactant insertion, and consequent increase in membrane fluidity, are observed to be spatially heterogenous, i.e. manifested as 'patches' of increased membrane fluidity. At the cell population level, spatially heterogeneous activity of surfactant is also manifested, with certain cells displaying high permeability amongst a 'background' population. We propose that this heterogeneity is further manifested in a broad profile of intracellular and nuclear exposure levels to a model drug (doxorubicin) observed in cell population. The study points to heterogeneous nature of surfactant effects at cell membrane and cells in population levels.

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BACKGROUND: The skin offers various benefits and potential for peptide delivery if its barrier performance can be reduced temporarily and reversibly. As peptides possess high molecular weight, hydrophilic nature (in most cases), and ionizable groups in the structure, their skin delivery is highly challenging. Apart from this, they are susceptible to the proteolytic enzymes in the skin. Anti-wrinkle peptides, like other peptides, suffer from insufficient skin permeability, while most of them must penetrate deep in the skin to present their efficacy. Although the cellular studies indicate the effectiveness of such peptides, without the ability to permeate the skin sufficiently, this efficacy is useless. Poor skin permeability of anti-wrinkle peptides has led to ongoing research for finding feasible and noninvasive enhancement methods that would be desirable for consumers of cosmetic products. METHOD: In this paper, the possibility of skin permeation of anti-wrinkle peptides as well as the chemical, physical, and encapsulation approaches that have been employed to date to increase permeability of these difficult molecules are thoroughly reviewed. RESULTS: Most anti-wrinkle peptides are not appropriate candidates for skin permeation and the use of enhancement methods is essential to increase their permeability. To do so, only some permeability enhancement approaches have been applied so far, including chemical modification with hydrophobic moieties or cell penetrating peptides, metal complexation, chemical permeation enhancers, iontophoresis, microneedles, and encapsulation in nanocarriers. The results of studies published on the skin permeability of anti-wrinkle peptides carnosine, GHK, PKEK, GEKG, GQPR, and KTTKS indicate that the skin permeability of these peptides can be successfully increased. CONCLUSION: Although the skin permeability of most anti-wrinkle peptides is not high enough and most anti-wrinkle peptides might not reach their targets in the skin at right concentrations, their permeability can be increased to therapeutic concentrations using various enhancement approaches.

CONTEXTE: La peau offre divers avantages et a la faculté de recevoir des peptides si l'on parvient à réduire temporairement et de manière réversible sa capacité à fonctionner comme une barrière. Comme les peptides ont un poids moléculaire élevé, une nature hydrophile (dans la plupart des cas) et possèdent des groupes ionisables dans leur structure, il est très difficile d'en faire bénéficier la peau. En outre, ils sont sensibles aux enzymes protéolytiques de la peau. Les peptides antirides, comme d'autres peptides, souffrent d'une capacité insuffisante de perméation de la peau ; or, la plupart d'entre eux doivent y pénétrer profondément pour avoir une efficacité. Bien que les études cellulaires indiquent l'efficacité de ces peptides, s'ils sont incapables de pénétrer suffisamment la peau, cette efficacité est inopérante. Face à cette perméabilité médiocre de la peau aux peptides antirides, des recherches sont menées actuellement pour trouver des méthodes d'amélioration à la fois réalisables et non invasives, qui soient attractives pour les consommateurs de produits cosmétiques. MÉTHODE: Dans cet article, nous étudions de manière approfondie la possibilité de perméation des peptides antirides à travers l'épiderme, ainsi que les approches chimiques, physiques et d'encapsulation utilisées à ce jour pour augmenter l'aptitude à la perméation de ces molécules difficiles. RÉSULTATS: La plupart des peptides antirides ne sont pas de bons candidats à la perméation de l'épiderme, et il est essentiel d'avoir recours à des méthodes de renforcement pour augmenter leur capacité de pénétration. Pour ce faire, seules certaines approches de renforcement de la perméation ont été appliquées jusqu'à présent : une modification chimique avec des fractions hydrophobes ou des peptides pénétrants la cellule ; la complexation métallique ; les amplificateurs de perméation chimique ; l'iontophorèse ; les micro-aiguilles et l'encapsulation dans les nano supports. Les résultats des études publiées sur la perméabilité de l'épiderme aux peptides antirides que sont la carnosine, le GHK, le PKEK, le GEKG, le GQPR et le KTTKS indiquent que l'augmentation de la capacité de perméation de l'épiderme de ces peptides est possible et donne de bons résultats. CONCLUSION: Bien que la capacité de perméation de la plupart des peptides antirides ne soit pas suffisamment élevée et qu'ils n'atteignent pas leurs cibles dans la peau aux bonnes concentrations, cette capacité peut être augmentée jusqu'à des concentrations thérapeutiques en recourant à diverses approches de renforcement.

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Ultrasound-facilitated transmembrane permeability enhancement has attracted broad attention in the treatment of central nervous system (CNS) diseases, by delivering gene/drugs into the deep site of brain tissues with a safer and more effective way. Although the feasibility of using acoustically vaporized nanodroplets to open the blood-brain-barrier (BBB) has previously been reported, the relevant physical mechanisms and impact factors are not well known. In the current study, a nitrocellulose (NC) membrane was used to mimic the multi-layered pore structure of BBB. The cavitation activity and the penetration ability of phase-changed nanodroplets were systemically evaluated at different concentration levels, and compared with the results obtained for SonoVue microbubbles. Passive cavitation detection showed that less intensified but more sustained inertial cavitation (IC) activity would be generated by vaporized nanodroplets than microbubbles. As the results, with a sufficiently high concentration (∼5 × 108/mL), phase-changed nanodroplets were more effective than microbubbles in enabling a fluorescent tracer agent (FITC, 150 kDa) to penetrate deeper and more homogeneously through the NC membrane, and a positive correlation was observed between accumulated IC dose and the amount of penetrated FITC. In vivo studies further confirmed acoustically vaporized nanodroplets performed better than microbubbles by opening the BBB in rats' brains. These results indicated that phase-changed nanodroplets can be used as a safe, efficient and durable agent to achieve satisfactory cavitation-mediated permeability enhancement effect in biomedical applications.

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Among many methods to mitigate the solubility limitations of drug compounds, amorphous solid dispersion (ASD) is considered to be one of the most promising strategies to enhance the dissolution and bioavailability of poorly water-soluble drugs. The enhancement of ASD in the oral absorption of drugs has been mainly attributed to the high apparent drug solubility during the dissolution. In the last decade, with the implementations of new knowledge and advanced analytical techniques, a drug-rich transient metastable phase was frequently highlighted within the supersaturation stage of the ASD dissolution. The extended drug absorption and bioavailability enhancement may be attributed to the metastability of such drug-rich phases. In this paper, we have reviewed (i) the possible theory behind the formation and stabilization of such metastable drug-rich phases, with a focus on non-classical nucleation; (ii) the additional benefits of the ASD-induced drug-rich phases for bioavailability enhancements. It is envisaged that a greater understanding of the non-classical nucleation theory and its application on the ASD design might accelerate the drug product development process in the future.

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The ability of a water-soluble, single-stranded ß-1,3/1,6-glucan (ssß-glucan), recovered by hydrothermal treatment, to enhance the solubility and membrane permeability of poorly water-soluble compounds was examined. As a poorly water-soluble model compound, quercetin (QUE) was used. The aqueous solubility of spray-dried particles (SDPs) of QUE/ssß-glucan was significantly enhanced compared with that of the untreated QUE powder and the physical mixture of QUE/ssß-glucan. Fourier-transform infrared spectra and small-angle X-ray scattering suggested strong interactions between ssß-glucan and QUE in the SDPs, which was attributable to QUE entrapment in the helical ssß-glucan structure. The amount of QUE infused into Caco-2 cells from QUE/ssß-glucan SDPs was 16-fold and 5-fold higher than the amount infused from untreated QUE powder and the physical mixture of QUE/ssß-glucan, respectively. These results showed that water-soluble ssß-glucan improved QUE dissolution and membrane permeability.

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Chemical modification of chitosan derivatives with hydrophobic fatty acids to enhance their self-aggregation behavior is well established. Previously our group reported low molecular weight carboxymethyl chitosan (CMCS) which showed enhancement in apparent permeability of hydrophobic drug, tamoxifen. Further extension to this work, herein we synthesize a new polymer of oleic acid grafted low molecular weight carboxymethyl chitosan (OA-CMCS) for maneuvering biopharmaceutical performance of poorly water soluble drugs. This polymer was designed and synthesized via amidation reaction and well characterized by analytical tools like 1H-NMR and FT-IR spectroscopy. OA-CMCS conjugate easily self-organized into micelles like structure in an aqueous medium and showed a low critical micellar concentration of 1 µg/mL. Poorly water-soluble drug, docetaxel (DTX) was used as a model drug in this study. Optimization of variables resulted in the formation of spherical DTX loaded OA-CMCS micelles in the size range of 213.4 ± 9.6 nm with an entrapment efficiency of 57.26 ± 1.25%. DTX loaded OA-CMCS micelles showed slow and sustained DTX release behavior in simulated body fluid during in vitro release study. The permeability of DTX loaded OA-CMCS micelles across the gastrointestinal tract were investigated by in vitro Caco-2 cells model. The apparent permeability of DTX loaded OA-CMCS micelles improved up to 6.57-fold in comparison to free DTX suspension which indicates the increase in paracellular absorption of DTX. Additionally, in vivo pharmacokinetic study demonstrates an increase in Cmax (1.97-fold) and AUC (2.62-fold) for DTX loaded OA-CMCS micelles compared to free DTX suspension. Hence, we propose OA-CMCS as a promising cargo to incorporate drugs for enhancement of biopharmaceutical performance.

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The effect of composite formation between α-glucosyl stevia (Stevia-G) and hydrophilic polymers on solubility and permeability enhancement of quercetin hydrate (QUE) was evaluated. Polyvinylpyrrolidone K-30 (PVP), hydroxypropyl methylcellulose 2910-E (HPMC), and hydroxypropyl cellulose SSL (HPC) were selected as candidate hydrophilic polymers. Fluorescence studies with pyrene and curcumin suggested composite formation occurs between Stevia-G aggregate and polymers. Furthermore, the strength of interaction between Stevia-G aggregate and polymers was as follows: PVP > HPMC > HPC. Evaporated particles (EVPs) of QUE with Stevia-G and polymers showed synergic QUE solubility enhancement. Solubility of QUE from the EVPs was enhanced in the following order: Stevia-G/PVP > Stevia-G/HPMC > Stevia-G/HPC, in accordance with the degree of interaction. Enhanced membrane permeability of QUE from the EVPs of Stevia-G/PVP was confirmed using Caco-2 cells. The amount of QUE that permeated Caco-2 cells from the EVPs of Stevia-G/PVP was 13.7-, 4.7-, and 2.1-fold higher than that of the untreated QUE powder, EVPs of Stevia-G, and EVPs of PVP, respectively. These results indicated that the composite formed by Stevia-G and PVP can dramatically enhance the solubility and membrane permeability of QUE.

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The oral delivery of cancer chemotherapeutic drugs is challenging due to low bioavailability, gastrointestinal side effects, first-pass metabolism and P-glycoprotein efflux pumps. Thus, chemotherapeutic drugs, including Docetaxel, are administered via an intravenous route, which poses many disadvantages of its own. Recent advances in pharmaceutical research have focused on designing new and efficient drug delivery systems for site-specific targeting, thus leading to improved bioavailability and pharmacokinetics. A decent number of studies have been reported for the safe and effective oral delivery of Docetaxel. These nanocarriers, including liposomes, polymeric nanoparticles, metallic nanoparticles, hybrid nanoparticles, dendrimers and so on, have shown promising results in research papers and clinical trials. The present article comprehensively reviews the research efforts made so far in designing various advancements in the oral delivery of Docetaxel. Different strategies to improve oral bioavailability, prevent first-pass metabolism and inhibition of efflux pumping leading to improved pharmacokinetics and anticancer activity are discussed. The final portion of this review article presents key issues such as safety of nanomaterials, regulatory approval and future trends in nanomedicine research.

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The permeability enhancement effect of oleic acid (OA) and propylene glycol (PG) as well as their (1:1 v/v) combined mixture was studied using rat skin. The percutaneous drug administration is a challenge and an opportunity for drug delivery. To date, there is limited research that illustrates the mechanism of penetration enhancers and their combinations on the skin. This project aims to explore the skin diffusion and penetration enhancement of PG, OA, and a combination of PG-OA (1:1 v/v) on rat skin and to identify the potential synergistic effect of the two enhancers utilizing Raman spectroscopy. Dissected dorsal skin was treated with either PG or OA or their combination for predetermined time intervals after which the Raman spectra of the treated skin were collected with the enhancer. A spectrum of the wiped and the washed skin were also collected. The skin integrity was tested before and after exposure to PG. The skin histology proved that the skin integrity has been maintained during experiments and the results indicated that OA disrupted rat skin lipid as evident by changes in the lipid peak. The results also showed that PG and OA improved the diffusion of each other and created faster, yet reversible changes of the skin peaks. In conclusion, Raman spectroscopy is a potential tool for ex vivo skin diffusion studies. We also concluded that PG and OA have potential synergistic reversible effect on the skin.

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Crown ethers are cyclic molecules consisting of a ring containing several ether groups. The most common and important members of this series are 12-crown-4 (12C4), 15-crown-5 (15C5), and 18-crown-6 (18C6). These container molecules have the ability to sequester metal ions, and their complexes with drugs are able to traverse cell membranes. This study investigated 12C4, 15C5, and 18C6 for their ability to increase solubility of ocular drugs and enhance their penetration into the cornea. Phase solubility analysis determined crown ethers' ability to enhance the solubility of riboflavin, a drug used for the therapy of keratoconus, and these solutions were investigated for ocular drug permeation enhancing properties. Atomic absorption spectroscopy demonstrated crown ether solutions' ability to sequester Ca2+ from corneal epithelia, and crown ether mediated adsorption of riboflavin into the stroma was investigated. Induced corneal opacity studies assessed potential toxicity of crown ethers. Crown ethers enhanced riboflavin's aqueous solubility and its penetration into in vitro bovine corneas; the smaller sized crown ethers gave greatest enhancement. They were shown to sequester Ca2+ ions from corneal epithelia; doing so loosens cellular membrane tight junctions thus enhancing riboflavin penetration. Induced corneal opacity was similar to that afforded by benzalkonium chloride and less than is produced using polyaminocarboxylic acids. However, in vivo experiments performed in rats with 12C4 did not show any statistically significant permeability enhancement compared to enhancer-free formulation.

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In recent years, biological products (biologics), including blood components, recombinant therapeutic proteins, antibodies, gene therapeutic materials, and so on, have been produced by biotechnology methods and other novel technologies. These products are essential therapeutic materials in progressive medicine. However, we often encounter the lower permeability of these biologics through biomembranes, due to their high molecular mass. In the last three decades, we have investigated drug delivery systems, including several enhancement methods for the permeability of biologics such as recombinant therapeutic proteins and viral vectors in epithelial cells. This review focuses the development of novel delivery systems for biologics in rectal and nasal administration, and includes an interesting observation of modulators of the tight junction (TJ) function. From cellular biology perspective, the interaction between permeability enhancing materials and targeted molecules in the TJ of epithelial cells was investigated. We elucidated that a TJ modulator will interact with a major constituent protein, for instance claudins, in playing an essential role in the tissue-specific barrier function of the TJ. Furthermore, useful enhancement of gene transfer in cells (for instance, in Caco-2 cells) was found in the combination of an adenovirus vector and capric acid sodium salt (C10), a TJ modulator.

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AIM: To examine if rubusoside (RUB) can overcome insolubility of betulonic acid (BEA), it can be accurately evaluated for its intrinsic activity against cancer in cell culture and in tumor animal models. MATERIALS & METHODS: By processing RUB and BEA together using a solvent evaporation method, a joint nanoparticulate structure is formed, designated as BEA-NP. RESULTS: BEA-NP was found over three-times more permeable than that solubilized by DMSO in Caco-2 cell monocultures. In an in vivo efficacy study, the tumor growth in the S180 berry mice orally dosed with BEA-NP at 75 mg/kg was inhibited by 50%. CONCLUSION: RUB was effective in solubilizing BEA, maintaining its cytotoxicity, enhancing its permeability and reducing tumor growth when orally administered.

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OBJECTIVE: The present research work was intended to develop and optimize sustained release of biodegradable chitosan nanoparticles (CSNPs) as delivery vehicle for sodium cromoglicate (SCG) using the circumscribed Box-Behnken experimental design (BBD) and evaluate its potential for oral permeability enhancement. METHODS: The 3-factor, 3-level BBD was employed to investigate the combined influence of formulation variables on particle size and entrapment efficiency (%EE) of SCG-CSNPs prepared by ionic gelation method. The generated polynomial equation was validated and desirability function was utilized for optimization. Optimized SCG-CSNPs were evaluated for physicochemical, morphological, in-vitro characterizations and permeability enhancement potential by ex-vivo and uptake study using CLSM. RESULTS: SCG-CSNPs exhibited particle size of 200.4 ± 4.06 nm and %EE of 62.68 ± 2.4% with unimodal size distribution having cationic, spherical, smooth surface. Physicochemical and in-vitro characterization revealed existence of SCG in amorphous form inside CSNPs without interaction and showed sustained release profile. Ex-vivo and uptake study showed the permeability enhancement potential of CSNPs. CONCLUSIONS: The developed SCG-CSNPs can be considered as promising delivery strategy with respect to improved permeability and sustained drug release, proving importance of CSNPs as potential oral delivery system for treatment of allergic rhinitis. Hence, further studies should be performed for establishing the pharmacokinetic potential of the CSNPs.

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