International Journal of Pharmaceutics

Publisher: Elsevier

Journal description

The International Journal of Pharmaceutics provides a medium for the publication of innovative papers, reviews, mini-reviews, short communications and notes dealing with physical, chemical, biological, microbiological and engineering studies related to the conception, design, production, characterisation and evaluation of drug delivery systems in vitro and in vivo. "Drug" is defined as any therapeutic or diagnostic entity, including oligonucleotides, gene constructs and radiopharmaceuticals. Areas of particular interest include: physical pharmacy; polymer chemistry and physical chemistry as applied to pharmaceutics; excipient function and characterisation; biopharmaceutics; absorption mechanisms; membrane function and transport; novel routes and modes of delivery; responsive delivery systems, feedback and control mechanisms including biosensors; applications of cell and molecular biology to drug delivery; prodrug design; bioadhesion (carrier-ligand interactions); and biotechnology (protein and peptide delivery). Editorial Policy The over-riding criteria for publication are originality, high scientific quality and interest to a multidisciplinary audience. Papers not sufficiently substantiated by experimental detail will not be published. Any technical queries will be referred back to the author, although the Editors reserve the right to make alterations in the text without altering the technical content. Manuscripts submitted under multiple authorship are reviewed on the assumption that all listed authors concur with the submission and that a copy of the final manuscript has been approved by all authors and tacitly or explicitly by the responsible authorities in the laboratories where the work was carried out. If accepted, the manuscript shall not be published elsewhere in the same form, in either the same or another language, without the consent of the Editors and Publisher. Authors must state in a covering letter when submitting papers for publication the novelty embodied in their work or in the approach taken in their research. Routine bioequivalence studies are unlikely to find favour. No paper will be published which does not disclose fully the nature of the formulation used or details of materials which are key to the performance of a product, drug or excipient. Work which is predictable in outcome, for example the inclusion of another drug in a cyclodextrin to yield enhanced dissolution, will not be published unless it provides new insight into fundamental principles.

Current impact factor: 3.65

Impact Factor Rankings

2015 Impact Factor Available summer 2016
2014 Impact Factor 3.65
2013 Impact Factor 3.785
2012 Impact Factor 3.458
2011 Impact Factor 3.35
2010 Impact Factor 3.607
2009 Impact Factor 2.962
2008 Impact Factor 3.061
2007 Impact Factor 2.408
2006 Impact Factor 2.212
2005 Impact Factor 2.156
2004 Impact Factor 2.039
2003 Impact Factor 1.539
2002 Impact Factor 1.495
2001 Impact Factor 1.419
2000 Impact Factor 1.024
1999 Impact Factor 0.952
1998 Impact Factor 0.978
1997 Impact Factor 0.898

Impact factor over time

Impact factor

Additional details

5-year impact 4.01
Cited half-life 7.30
Immediacy index 0.53
Eigenfactor 0.04
Article influence 0.77
Website International Journal of Pharmaceutics website
ISSN 1873-3476

Publisher details


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  • Conditions
    • Authors pre-print on any website, including arXiv and RePEC
    • Author's post-print on author's personal website immediately
    • Author's post-print on open access repository after an embargo period of between 12 months and 48 months
    • Permitted deposit due to Funding Body, Institutional and Governmental policy or mandate, may be required to comply with embargo periods of 12 months to 48 months
    • Author's post-print may be used to update arXiv and RepEC
    • Publisher's version/PDF cannot be used
    • Must link to publisher version with DOI
    • Author's post-print must be released with a Creative Commons Attribution Non-Commercial No Derivatives License
    • Publisher last reviewed on 03/06/2015
  • Classification

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Gastric cancer is a highly lethal malignancy and its 5-year survival rate remains depressed in spite of multiple treatment options. Targeting drug delivery to tumor vasculature may be a promising strategy for gastric cancer therapy, for it can block the nutrition source of tumor and inhibit the metastasis and invasion in a certain extent. In present study, we have prepared the drug-targeting delivery system of peptide GX1-mediated anionic liposomes carrying adenoviral vectors (GX1-Ad5-AL), in which the tumor suppressor gene of PTEN was integrated into DNA of Ad5 and the GX1 peptide could play targeting role to vascular of gastric cancer. The inhibition ability of GX1-Ad5-AL to human gastric cancer cell lines (SGC-7901) and human umbilical vein endothelial cells (HUVEC) was evaluated by MTT assay. Further, the cell migration assay was carried out in transwell inserts and the cells uptaking of GX1-Ad5-AL was detected by confocal laser scanning microscopy. The experimental results indicated that the average cell proliferation inhibition rates resulted from the drug delivery system of GX1-Ad5-AL in SGC-7901 and HUVEC were respectively 68.36% and 64.13%, which were higher than that resulted from GX1 or Ad5-AL. Meanwhile, results of cell migration experiment demonstrated that GX1-Ad5-AL could significantly suppress the migration of gastric cancer cell of SGC-7901. Moreover, both the imaging from confocal laser scanning microscopy and the quantitative analysis of fluorescence intensity showed that, GX1-Ad5-AL was more easily uptaken by SGC-7901 cells, as compared to Ad5-AL. Therefore, the formulation of GX1-Ad5-AL was effective for enhancing the inhibition effect and suppressing the migration of gastric cancer vascular endothelial cells.
    International Journal of Pharmaceutics 11/2015; DOI:10.1016/j.ijpharm.2015.11.019
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    ABSTRACT: The manufacture of porous polycaprolactone (PCL) scaffolds containing three different drugs, namely 5-fluorouracil, nicotinamide and triflusal, was investigated in this work with the aim of obtaining bioactive systems with controlled drug delivery capabilities. The scaffolds were prepared by means of a supercritical CO2 (scCO2) foaming technique by optimizing the drug loading process. This was achieved by dissolving the drugs in organic solvents miscible with scCO2 and by mixing these drug/solvent solutions with PCL powder. The as prepared mixtures were further compressed to eliminate air bubbles and finally processed by the scCO2 foaming technique. ScCO2 saturation and foaming conditions were optimized to create the porosity within the samples and to allow for the concomitant removal of the organic solvents. Physical and chemical properties of porous scaffolds, as well as drug content and delivery profiles, were studied by HPLC. The results of this study demonstrated that the composition of the starting PCL/drug/solvent mixtures affected polymer crystallization, scaffold morphology and pore structure features. Furthermore, it was found that drug loading efficiency depended on both initial solution composition and drug solubility in scCO2. Nevertheless, in the case of highly scCO2-soluble drugs, such as triflusal, loading efficiency was improved by adding a proper amount of free drug inside of the pressure vessel. The drug delivery study indicated that release profiles depended mainly upon scaffolds composition and pore structure features.
    International Journal of Pharmaceutics 11/2015; DOI:10.1016/j.ijpharm.2015.11.012
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    ABSTRACT: The limited solubility of BCS class II drugs diminishes their dissolution and thus reduces their bioavailability. Our aim in this study was to develop and optimize a spray dried emulsion containing indomethacin as a model for Class II drugs, Labrasol(®)/Transuctol(®) mixture as the oily phase, and maltodextrin as a solid carrier. The optimization was carried out using a 2(3) full factorial design based on two independent variables, the percentage of carrier and concentration of Poloxamer(®)188. The effect of the studied parameters on the spray dried yield, loading efficiency and in vitro release were thoroughly investigated. Furthermore, physicochemical characterization of the optimized formulation was performed. In vivo bioavailability, ulcerogenic capability and histopathological features were assessed. The results obtained pointed out that poloxamer 188 concentration in the formulation was the predominant factor affecting the dissolution release, whereas the drug loading was driven by the carrier concentration added. Moreover, the yield demonstrated a drawback by increasing both independent variables studied. The optimized formulation presented a complete release within two minutes thus suggesting an immediate release pattern as well, the formulation revealed to be uniform spherical particles with an average size of 7.5μm entrapping the drug in its molecular state as demonstrated by the DSC and FTIR studies. The in vivo evaluation, demonstrated a 10-fold enhancement in bioavailability of the optimized formulation, with absence of ulcerogenic side effect compared to the marketed product. The results provided an evidence for the significance of spray dried emulsion as a leading strategy for improving the solubility and enhancing the bioavailability of class II drugs.
    International Journal of Pharmaceutics 11/2015; DOI:10.1016/j.ijpharm.2015.11.009
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    ABSTRACT: The sorption of a drug by an infusion set may dramatically reduce the drug delivery efficiency. In this paper, we investigated how the drug sorption, in static conditions, is affected by the plasticizer's nature and ratio in the case of plasticized PVC, one of the most common material for infusion set tubing. Within the study, the drug concentration in diazepam solutions was studied after contact with PVC films containing different amounts of DEHP, DEHT, TOTM and DINCH plasticizers. Moreover the partition coefficients between material and water were calculated. The drug sorption levels were equivalent for the different plasticizers and there was a plasticizer ratio for which the drug uptake was enhanced. As a consequence, the amount of sorbed drug might not be only linked to the amount of plasticizer in the film and to the solubility of the drug in the plasticizer alone: it must probably depend on specific interactions between plasticizer and PVC.
    International Journal of Pharmaceutics 11/2015; DOI:10.1016/j.ijpharm.2015.11.004
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    ABSTRACT: Polymeric microparticle(MPs)-in-gel formulations for extended delivery of octreotide were developed. We investigated influence of polymer composition on acylation of octreotide and kinetics of release during in vitro release from biodegradable polymeric formulations. Polycaprolactone (PCL), polylactic acid (PLA), polyglycolic acid (PGA) and polyethylene glycol (PEG) based triblock (TB≈PCL10k-PEG2k-PCL10k) and pentablock (PBA≈PLA3k-PCL7k-PEG2k-PCL7k-PLA3k and PBB≈PGA3k-PCL7k-PEG2k-PCL7k-PGA3k) polymers were investigated. Octreotide was encapsulated in MPs using methanol-oil/water emulsion solvent evaporation method. The particles were characterized for size, morphology, encapsulation efficiency, drug loading and in vitro release. Release samples were subjected to HPLC analysis for quantitation and HPLC-MS analysis for identification of native and chemically modified octreotide adducts. Entrapment efficiency of methanol-oil/water method with TB, PBA and PBB polymers were 45%, 60%, and 82%, respectively. A significant fraction of released octreotide was acylated from lactide and glycolide based PBA (53%) and PBB (92%) polymers. Substantial amount of peptide was not released from PBB polymers after 330 days of incubation. Complete release of octreotide was achieved from TB polymer over a period of 3 months with minimal acylation of peptide (13%). PCL based polymers resulted in minimal acylation of peptide and hence may be suitable for extended peptide and protein delivery. Conversely, polymers having PLA and PGA blocks may not be appropriate for peptide delivery due to acylation and incomplete release.
    International Journal of Pharmaceutics 11/2015; DOI:10.1016/j.ijpharm.2015.11.002
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    ABSTRACT: Protein drug products play an important role in the treatment of severe diseases. However, due to the instability of these complex molecules, protein aggregates can form which can compromise drug safety and efficacy including immunogenic reactions. In-line filtration during the administration of these drugs can serve as a final safeguarding step to protect patients from risks associated with proteinaceous particles. A unique analysis of more than 300 marketed protein drug products revealed that already around 16% of all these products are filtered during preparation or administration. Further, the research revealed that no standardized filtration practice exists. Broad variances regarding filter membrane or pore size are found and sometimes no specifications are mentioned at all. The benefits as well as possible negative impacts of filtration like filter shedding, extractables or drug adsorption are critically assessed. Several proposals to improve the current filtration practice and to expand the number of in-line filtered protein drug products are made. The suggestions include the demand for the specific usage of one filter membrane type, the establishment of a filtration routine for unfiltered protein drugs and a statistical analysis between filtered and non-filtered products with similar formulations to identify possible differences in the immunogenicity rate.
    International Journal of Pharmaceutics 11/2015; DOI:10.1016/j.ijpharm.2015.10.082
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    ABSTRACT: Barrier coatings are frequently employed on solid oral dosage forms under the assumption that they prevent moisture sorption into tablet cores thereby averting premature degradation of moisture-sensitive active ingredients. However, the efficacy of moisture barrier coatings remains unproven and they may actually accelerate degradation. This study aimed to investigate the barrier performance of four coating systems following application onto a low hygroscopic tablet formulation containing aspirin as a model moisture sensitive drug. Tablets were prepared by direct compaction and coated with aqueous dispersions of Eudragit(®) L30 D-55, Eudragit(®) EPO, Opadry(®) AMB and Sepifilm(®) LP at the vendors' recommended weight gains. Moisture uptake was studied by dynamic vapour sorption at 0 and 75% RH (25°C). Accelerated stability studies were undertaken at 75% RH/25°C for 90 days and HPLC assay was used to determine aspirin content. Uncoated tablet cores equilibrated rapidly and took up very little water (0.09%). The mean water uptake for coated cores was higher than for the uncoated formulation and varied as follows: 0.19% (Eudragit(®) L30 D-55), 0.35% (Opadry(®) AMB), 0.49% (Sepifilm(®) LP) and 0.76% (Eudragit(®) EPO). The level of aspirin decreased in all the samples such that by the time the study was terminated, the % mean aspirin recovered was as follows: uncoated cores 80.0%; Eudragit® L30 D-55 coated cores 78.8%; Opadry(®) AMB coated cores 76.2%, Sepifilm(®) LP coated cores 76.0% and Eudragit(®) EPO coated samples 66.5%. From these results, it is concluded that the efficacy of moisture barrier polymer coatings on low hygroscopic cores is limited, and application of these coatings can, instead, enhance drug degradation in solid dosage forms.
    International Journal of Pharmaceutics 11/2015; DOI:10.1016/j.ijpharm.2015.10.068
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    ABSTRACT: Melt granulation in fluid bed processors is an emerging technique, but literature data regarding the modeling of this granulation method are lacking. In the present study different techniques (response surface analysis, multilayer perceptron neural network, and partial least squares method) were applied for modeling of spray-on fluidized bed melt granulation. Experiments were organized in line with central composite design. The effect of binder content and spray air pressure on granule properties was evaluated. The results obtained indicate that binder content can be identified as a critical factor controlling the granule size and size distribution. It was found that agglomeration mechanism involved, i.e. granule shape, can be greatly influenced by binder properties. The spray air pressure was identified as critical process parameter affecting granule flowability. The results presented indicate that application of in silico tools enables enhanced understanding and better control of novel pharmaceutical processes, such as melt granulation in fluidized bed. The artificial neural networks and partial least squares method were found to be superior to response surface methodology in prediction of granule properties. According to the results obtained, application of more advanced empirical modeling techniques complementary to design of experiments can be a suitable approach in defining the design space and optimization of spray-on fluidized bed melt granulation.
    International Journal of Pharmaceutics 11/2015; DOI:10.1016/j.ijpharm.2015.11.001
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    ABSTRACT: The present study evaluates the feasibility of particulate carriers of a biodegradable polymer polyethylene sebacate (PES) as an alternative to Freund's adjuvant in the design of a peptide vaccine formulation. The vaccine formulation comprised of PES and the antigen KLH conjugated 80kDaHSA peptide-1 dissolved in N-methyl-2-pyrrolidone (NMP)/NMP-water as solvent. The antigen revealed good stability and the formulations were readily syringeable. Intradermal injection of the formulations resulted in the formation of PES particulates in situ at the site of injection. The NMP formulations revealed larger particulates which elicited no immunogenic response when injected in rabbits. On the other hand the NMP-water formulation revealed formation of microparticles which were significantly smaller in size, in combination with a small fraction of nanoparticles. It elicited an antibody titer up to 1:3200 in rabbits following intradermal injection. Western blot confirmed generation of antibodies specific to the peptide. Contraceptive efficacy was confirmed by loss of sperm motility and head-to-head agglutination of sperms in the treatment group. Unlike the severe reactions observed with administration of Freund's adjuvant, only mild hypersensitivity reaction was observed with the PES formulations. The mild reaction coupled with the contraceptive efficacy observed suggested PES particulates as a viable alternative to Freund's adjuvant.
    International Journal of Pharmaceutics 11/2015; DOI:10.1016/j.ijpharm.2015.10.070
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    ABSTRACT: Current study was aimed to develop 200mg controlled release matrix tablets of Losartan potassium using ethocel 100 Premium and ethocel 100 FP premium as rate controlling polymer. In-vitro studies were performed according to USP Method-I in phosphate buffer (PH 6.8) using pharma test dissolution apparatus. The temperature of the dissolution medium was kept constant at 37 ± 0.5 (°)C at 100rpm. Flow properties, physical quality control tests, effect of polymer size and drug-to-polymers ratios were studied using different kinetics models such as 1st-order, Zero-order, Hixon Crowell model, Highuchi model and Power law. Difference factor f1 and similarity factor f2 were applied for dissolution profiles against Cardaktin® tablets used as a reference formulation. The matrices with polymer ethocel 100 FP premiums have prolonged the drug release rate as compared to polymer ethocel 100 premiums. The n values matrices with polymer ethocel grade 100 ranged from 0.603 to 0.857 indicating that the drug release occurred by anomalous non fickian diffusion kinetics while then value of reference Cardaktin® tablet was measured as 0.125 indicating that these tablets do not follow power law. The dissolution profiles of test formulations were different than that of reference Cardaktin®. This suggests the polymer Ethocel grade 100 can be proficiently incorporated in fabrication and development of once a day controlled release matrix tablets.
    International Journal of Pharmaceutics 11/2015; DOI:10.1016/j.ijpharm.2015.10.051
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    ABSTRACT: Pulsed laser deposition (PLD) method was used to obtain biovitroceramic thin film coatings on titanium substrates. The composition of the targets was selected from SiO2-CaO-P2O5-(CaF2) systems and the corresponding masses were prepared using the sol-gel method. The depositions were performed in oxygen atmosphere (100mTorr), while the substrates were heated at 400°C. The PLD deposited films were analysed through different experimental techniques: X-ray diffraction, scanning (SEM, EDX) and transmission (HRTEM, SAED) electron microscopy and infra-red spectroscopy coupled with optical microscopy. They were also biologically tested by in vitro cell culture and the contact angle was determined. The bioevaluation results indicate a high biocompatibilty of the obtained materials, demonstrating their potential use for biomedical applications.
    International Journal of Pharmaceutics 11/2015; DOI:10.1016/j.ijpharm.2015.10.083
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    ABSTRACT: Dosage forms with fixed dose combinations of drugs is a frequent and advantageous mode of administration, but their production involves a number of technological problems. Numerous interactions in a homogeneous vehicle may be avoided through the use of layered tablets. The mechanical properties of these dosage forms depend on numerous process parameters and material characteristics. The aim of the present study was a detailed investigation of the relationships between the surface characteristics and deformation properties of tableting materials and the tendency of bilayer tablets to undergo lamination. Bilayer tablets were compressed from unlubricated materials with different plastic-elastic properties and surface free energies according to a mixed 2 and 3-level half-replicated factorial design. The results revealed that the surface characteristics play the main role in the lamination of layered tablets and the effect of the plastic-elastic behavior cannot be interpreted without a knowledge of these properties.
    International Journal of Pharmaceutics 11/2015; DOI:10.1016/j.ijpharm.2015.10.061

  • International Journal of Pharmaceutics 11/2015; DOI:10.1016/j.ijpharm.2015.11.003
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    ABSTRACT: Effective drug delivery to the lungs by a DPI device requires the air-stream through the device to have sufficient power to aerosolise the powder. Furthermore, sufficient turbulence must be induced, along with particle-wall and particle-particle collisions, in order to de-aggregate small drug particles from large carrier particles. As a result, the emitted and the fine particle doses produced by many commercially available DPI devices tend to be strongly affected by the natural inter-patient variability of the inhaled air flow. The Nexthaler(®) is a multi-dose breath-actuated dry-powder inhaler with minimum drug delivery-flow rate dependency and incorporating a dose protector. The actuation mechanism of the dose-protector ensures that the dose is only exposed to the inhaled air flow if the flow has sufficient power to cause complete aerosolisation. For this study, a proprietary lactose placebo powder blend was filled into "transparent" Nexthalers(®) to allow application of high-speed imaging and particle image velocimetry (PIV) techniques to successfully interrogate and reveal details of the powder entrainment and emission processes coupled with characterisation of the flow environment in the vicinity of the mouthpiece exit. The study showed that fluidisation of the bulk of the powder occurs very quickly (∼20ms) after withdrawal of the dose protector followed by powder emission from the device within ∼50ms thereafter. The bulk of the metered placebo dose was emitted within 100-200ms. The visualisation study also revealed that a very small fraction of powder fines is emitted whilst the dose protector still covers the dosing cup as the flow rate through the device accelerates. The PIV results show that the flow exiting the device is highly turbulent with a rotating flow structure, which forces the particles to follow internal paths having a high probability of wall impacts, suggesting that the flow environment inside the Nexthaler(®) DPI will be very beneficial for carrier-drug de-aggregation.
    International Journal of Pharmaceutics 11/2015; DOI:10.1016/j.ijpharm.2015.10.072
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    ABSTRACT: Ethinylestradiol (EE) as a highly active and low dosed compound is prone to oxidative degradation. The stability of the drug substance is therefore a critical parameter that has to be considered during drug formulation. Beside the stability of the drug substance, granule particle size and moisture are critical quality attributes (CQA) of the fluid bed granulation process which influence the tableting ability of the resulting granules. Both CQA should therefore be monitored during the production process by process analytic technology (PAT) according to ICH Q8. This work focusses on the effects of drying conditions on the stability of EE in a fluid-bed granulation process. We quantified EE degradation products 6-alpha-hydroxy-EE, 6-beta-hydroxy-EE, 9(11)-dehydro-EE and 6-oxo-EE during long time storage and accelerated conditions. PAT-tools that monitor granule particle size (Spatial filtering technology) and granule moisture (Microwave resonance technology) were applied and compared with off-line methods. We found a relevant influence of residual granule moisture and thermic stress applied during granulation on the storage stability of EE, whereas no degradation was found immediately after processing. Hence we conclude that drying parameters have a relevant influence on long term EE stability.
    International Journal of Pharmaceutics 11/2015; DOI:10.1016/j.ijpharm.2015.10.074
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    ABSTRACT: The aim of the present study was to evaluate the gel-forming polysaccharide psyllium in the preparation of mucoadhesive patches for the controlled release of chlorhexidine (CHX) to treat pathologies in the oral cavity, using the casting-solvent evaporation technique. A number of different film-forming semi-synthetic polymers, such as sodium carboxymethyl cellulose (SCMC) and hydroxypropylmethyl cellulose (HPMC) were evaluated for comparison. The patch formulations were characterized in terms of drug content, morphology surface, swelling and mucoadhesive properties, microbiology inhibition assay and in vitro release tests. Three ex-vivo testswere carried out using porcine mucosa: an alternative dissolution test using artificial saliva that allows contemporary measurement of dissolution and mucoadhesion, a permeation test through the mucosa and the measurement of mucoadhesion using a Nouy tensile tester, as the maximum force required for the separation of the patch from the mucosa surface. The patches were also examined for determination of the minimum inhibitory concentration in cultures of Escherichiacoli and Staphylococcusaureus. All the patches incorporating psyllium were found suitable in terms of external morphology, mucoadhesion and controlled release of the drug: in the presence of psyllium the drug displays prolonged zero-order release related to slower swelling rate of the system.
    International Journal of Pharmaceutics 11/2015; DOI:10.1016/j.ijpharm.2015.10.077
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    ABSTRACT: Oral administration of insulin remains a challenge due to its poor enzymatic stability and inefficient permeation across epithelium. We herein developed a novel self-assembled polyelectrolyte complex nanoparticles by coating insulin-loaded dodecylamine-graft-γ-polyglutamic acid micelles with trimethyl chitosan (TMC). The TMC material was also conjugated with a goblet cell-targeting peptide to enhance the affinity of nanoparticles with epithelium. The developed nanoparticle possessed significantly enhanced colloid stability, drug protection ability and ameliorated drug release profile compared with graft copolymer micelles or ionic crosslinked TMC nanoparticles. For in vitroevaluation, Caco-2/HT29-MTX-E12 cell co-cultures, which composed of not only enterocyte-like cells but also mucus-secreting cells and secreted mucus layer, were applied to mimic the epithelium. Intracellular uptake and transcellular permeation of encapsulated drug were greatly enhanced for NPs as compared with free insulin or micelles. Goblet cell-targeting modification further increased the affinity of NPs with epithelium with changed cellular internalization mechanism. The influence of mucus on the cell uptake was also investigated. Ex vivo performed with rat mucosal tissue demonstrated that the nanoparticle could facilitate the permeation of encapsulated insulin across the intestinal epithelium. In vivo study preformed on diabetic rats showed that the orally administered nanoparticles elicited a prolonged hypoglycemic response with relative bioavailability of 7.05%.
    International Journal of Pharmaceutics 11/2015; DOI:10.1016/j.ijpharm.2015.10.078