Drug Delivery (DRUG DELIV)

Publisher: Informa Healthcare

Journal description

Drug Delivery serves the academic and industrial communities with peer reviewed coverage of basic research, development, and application principles of drug delivery and targeting at molecular, cellular, and higher levels. Topics covered include all delivery systems and modes of entry, such as controlled release systems; microcapsules, liposomes, vesicles, and macromolecular conjugates; antibody targeting; protein/peptide delivery. Published articles present original research and critical reviews. The journal also presents letters to the editor, book reviews, and announcements of interest to the readership such as Patent Briefings, Literature Alerts, and Calendars of Events.

Current impact factor: 2.20

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 2.202
2012 Impact Factor 2.015
2011 Impact Factor 1.456
2010 Impact Factor 1.246
2009 Impact Factor 1.413
2008 Impact Factor 1.55
2007 Impact Factor 1.642
2006 Impact Factor 1.424
2005 Impact Factor 1.067
2004 Impact Factor 1.327
2003 Impact Factor 1.191
2002 Impact Factor 1.269
2001 Impact Factor 0.792
2000 Impact Factor 0.596
1999 Impact Factor 0.697

Impact factor over time

Impact factor
Year

Additional details

5-year impact 1.78
Cited half-life 5.90
Immediacy index 0.18
Eigenfactor 0.00
Article influence 0.38
Website Drug Delivery website
Other titles Drug delivery (Online), Drug delivery
ISSN 1071-7544
OCLC 41545589
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Informa Healthcare

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • 12 months embargo
  • Conditions
    • On author's personal website or institution website
    • Publisher copyright and source must be acknowledged
    • On a non-profit server
    • Must link to publisher version
    • Publisher's version/PDF cannot be used
    • NIH funded authors may post articles to PubMed Central for release 12 months after publication
    • Wellcome Trust authors may deposit in Europe PMC after 6 months
  • Classification
    ​ yellow

Publications in this journal

  • Drug Delivery 06/2015;
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    ABSTRACT: Archaeosomes as liposomes made with one or more ether lipids that are unique to the domain of Archaeobacteria, found in Archaea constitute a novel family of liposome. Achaean-type lipids consist of archaeol (diether) and/or caldarchaeol (tetraether) core structures. Archaeosomes can be produced using standard procedures (hydrated film submitted to sonication, extrusion and detergent dialysis) at any temperature in the physiological range or lower, therefore making it possible to encapsulate thermally stable compounds. Various physiological as well as environmental factors affect its stability. Archaeosomes are widely used as drug delivery systems for cancer vaccines, Chagas disease, proteins and peptides, gene delivery, antigen delivery and delivery of natural antioxidant compounds. In this review article, our major aim was to explore the applications of this new carrier system in pharmaceutical field.
    Drug Delivery 03/2015; DOI:10.3109/10717544.2015.1019653
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    ABSTRACT: The objective of this study is to investigate cellular uptake of prodrug-loaded nanoparticle (NP). Another objective is to study bioconversion of stereoisomeric dipeptide prodrugs of ganciclovir (GCV) including L-Val-L-Val-GCV (LLGCV), L-Val-D-Val-GCV (LDGCV) and d-Val-l-Val-GCV (DLGCV) in human corneal epithelial cell (HCEC) model. Poly(D,L-lactic-co-glycolic acid) (PLGA) NP encapsulating prodrugs of GCV were formulated under a double emulsion method. Fluorescein isothiocyanate isomer-PLGA conjugates were synthesized to fabricate biocompatible fluorescent PLGA NP. Intracellular uptake of FITC-labeled NP was visualized by a fluorescent microscope in HCEC cells. Fluorescent PLGA NP and non-fluorescent NP display similar hydrodynamic diameter in the range of 115-145 nm with a narrow particle size distribution and zeta potentials around -13 mV. Both NP types showed identical intracellular accumulation in HCEC cells. Maximum uptake (around 60%) was noted at 3 h for NP. Cellular uptake and intracellular accumulation of prodrugs are significantly different among three stereoisomeric dipeptide prodrugs. The microscopic images show that NPs are avidly internalized by HCEC cells and distributed throughout the cytoplasm instead of being localized on the cell surface. Following cellular uptake, prodrugs released from NP gradually bioreversed into parent drug GCV. LLGCV showed the highest degradation rate, followed by LDGCV and DLGCV. LLGCV, LDGCV and DLGCV released from NP exhibited superior uptake and bioreversion in corneal cells.
    Drug Delivery 03/2015; DOI:10.3109/10717544.2015.1023384
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    ABSTRACT: There is 25-35% mutation rate of p53 in cancerous neural cells and this rate reaches 70-76% in glioma cell line. Complement of wild-type p53 has become a potential strategy for protein therapy of cancerous neural cells. Here we investigated the feasibility of a novel RDP-p53 fusion protein for anti-proliferation of cancerous neural cell and the possible mechanism, which would provide an effective approach for targeted delivery of p53 protein to treat cancerous neural cells. The RDP-p53 fusion proteins are expressed in Escherichia coli, and they are labeled with FITC and rhodamine B by chemical modification. The fluorescence-labeled proteins are added to human hepatocellular carcinoma cells (HepG-2) and human neuroblastoma cells (SH-SY5Y) in order to investigate the possibility of RDP enhancing the cell uptake efficiency into neural cells as a cell-permeable carrier. The inhibitory effect of RDP-p53 on SH-SY5Y and human glioma cells (U251) was evaluated by MTT assay. Moreover, the anti-proliferation mechanism of RDP-p53 was determined by Apoptosis and Necrosis Assay Kit and flow cytometric analysis. The results showed that RDP-p53 could enter SH-SY5Y cells with high efficiency and selectively inhibit the growth of cancerous neural cells, including SH-SY5Y and U251. Also, cell apoptosis pathway and cell-cycle arrest at the G2/M phase were associated with the inhibition mechanism of RDP-p53 according to the data of flow cytometric analysis. RDP-p53 could be a novel antitumor candidate for targeting treatment of cancerous neural cells.
    Drug Delivery 03/2015; DOI:10.3109/10717544.2015.1013199
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    ABSTRACT: Abstract This study aimed to evaluate transdermal delivery of vancomycin hydrochloride using the combination of ethosomes as an encapsulating vesicle and iontophoresis. Ethosomes were prepared and evaluated in terms of electrochemical stability. Cathodal iontophoresis of negatively charged ethosomes and anodal iontophoresis of free drug solution and positively charged vesicles were conducted. The effect of current mode, density, concentration of drug and ionic strength was studied. In vivo study was performed by inducing mediastinitis in Sprague-Dawley rats using methicillin-resistant Staphylococcus aureus as infected pathogen, the mean bacterial count was compared between groups of rats, one of the treated groups received drug intramuscularly while the other group received vancomycin using iontophoretic delivery of optimized ethosomal formula. Ethosomes showed efficient electrochemical stability, cathodal iontophoresis of negatively charged vesicle (F2) showed maximum transdermal flux (550 µg/cm(2)/h) compared to free drug solution and other ethosomal formulae, transdermal flux was reduced by altering current mode from continuous to ON/OFF mode, reducing current density and by using normal saline as drug solvent; on the other hand, flux was potentiated by increasing drug concentration from 25 to 75 mg/ml. In vivo study revealed that there was a significant difference in terms of bacterial count between untreated and treated groups, while there was no statistically significant difference between the I.M. vancomycin treatment and treatment conducted by iontophoretic delivery of vancomycin encapsulated in ethosomal formula. Combination between ethosomes and iontophoresis had succeeded in delivering vancomycin transdermally.
    Drug Delivery 03/2015; DOI:10.3109/10717544.2015.1013200
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    ABSTRACT: Abstract Objective: To elucidate the transfected effect of albumin ultrasound microbubbles carrying peptide nucleic acids (PNAs) against c-myc gene to the vascular walls and their effect on the intimal proliferation induced by vascular denudation. Methods: A rabbit iliac artery intimal proliferation model was constructed and PNA against c-myc mRNA was designed and synthesized and was added to albumin solution before ultrasound microbubbles were prepared and encapsulated in matrix of albumin. The ultrasound microbubbles carrying PNA were transfected to intima under ultrasound exposure. The transfected effect was identified by a histochemical method and the expression of c-myc was detected by in situ hybridization. The proliferation of intimal smooth muscle cells was estimated by the expression of proliferative cell nuclear antigen (PCNA) of them. The intimal area and thickness were judged morphologically for intimal hyperplasia. Results: The ultrasound microbubbles with PNA were successfully prepared and c-myc PNA was transfected to vascular intimal cells. The expression of c-myc and PCNA by intimal vascular smooth muscle cells (vSMCs) was inhibited significantly and the intimal thickness and area were reduced remarkably. Conclusion: Transfection of c-myc PNA could inhibit proliferartion of vSMCs and intima in the rabbit iliac artery intimal proliferation model and the targeted transfection of albumin ultrasound microbubbles carrying PNA offers a feasible way to facilitate its access to specific cells in vivo and produce bioavailability.
    Drug Delivery 03/2015; DOI:10.3109/10717544.2015.1014947
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    ABSTRACT: Abstract Superparamagnetic iron oxide nanoparticles (SPIONs) have been the subject of extensive research due to their potential biomedical applications. In the present investigation, superparamagnetic FA-PEI-Fe3O4 were successfully prepared and evaluated as a targeted MRI contrast agent. FTIR characteristics, TGA, VSM, and MR imaging confirmed the composition and magnetic properties of the synthesized nanoparticles. TEM showed that FA-PEI-Fe3O4 were spherical in shape and well dispersed. The nanoparticles were superparamagnetic at room temperature with a saturation magnetization value of 67.1 emu/g. The nanoparticles showed higher uptake efficiency due to receptor-mediated endocytosis. Moreover, specificity of FA-PEI-Fe3O4 to target tumor cells was demonstrated by the increased nanoparticle uptake and significant contrast enhancement of KB cells over MCF7 cells. The competitive inhibition of FA-PEI-Fe3O4 by free FA further confirmed the specific interaction of this conjugate with FA receptors. In vivo MR imaging studies showed a decreased signal intensity and enhanced tumor contrast post-injection of FA-PEI-Fe3O4. These results indicate that FA-PEI-Fe3O4 can be used as a promising tumor-targeting agent as well as a T2 negative-contrast agent in MR imaging applications.
    Drug Delivery 02/2015; DOI:10.3109/10717544.2015.1006404
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    ABSTRACT: Abstract Context: Development of carvedilol-loaded transfersomes for intranasal administration to overcome poor nasal permeability and hepatic first pass effect so as to enhance its bioavailability. Objective: The purpose of this study was to develop carvedilol-loaded transfersomes containing different edge activators (EAs) then evaluating the in vivo behavior of the optimized formula in rabbits. Methods: The vesicles were prepared by incorporating different EAs including Span 20, Span 60, Tween 20, Tween 80, and sodium deoxycholate (SDC) in the lipid bilayer and each EA was used in three different ratios with respect to phosphatidylcholine (PC) including 95:5%, 85:15%, and 75:25% w/w (PC:EA). Evaluation of transfersomes was carried out in terms of shape, size, entrapment efficiency (EE), in vitro release, ex vivo permeation, confocal laser scanning microscopy (CLSM), and stability studies. The pharmacokinetic study of the optimized formula was conducted in rabbits. Results: The mean diameter of the vesicles was in the range of 295-443 nm. Transfersomes prepared with 95:5% (w/w) (PC:EA) ratio showed highest EE% where Span 60 gave the highest values. Whereas those prepared using 85:15% w/w ratio showed highest percentages of drug release where SDC was superior to other EAs. The developed transfersomes exhibited significantly higher amounts of carvedilol permeated through nasal mucosa. CLSM of formula T14 containing SDC with 85:15% (w/w) (PC:EA) ratio revealed high permeation across the nasal mucosa. Conclusion: The nanotransfersomal vesicles were significantly more efficient in nasal delivery of carvedilol with absolute bioavailability of 63.4%.
    Drug Delivery 02/2015; DOI:10.3109/10717544.2015.1013587
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    ABSTRACT: Abstract Delivery systems controlling drug release only in the colon holds great promises since they improve utilization of drug and decrease the dosing times comparison with conventional forms. The aim of the present study was to prepare polymeric microparticles on the basis of Ciprofloxacin via oral route for the treatment of inflammatory bowel disease. Ciprofloxacin was selected because of its extensive coverage for intestinal flora, relatively favorable side-effect profile and preliminary data suggesting its efficacy in the treatment of active Crohn's Disease. Microparticles were prepared using different acrylic compounds, namely Eudragit® RL (PO) and RS (PO) and a mixture of both. Spray-drying was used as a preparation method of Ciprofloxacin/Eudragit® microparticles using a Mini Spray Dryer B-290 (Büchi, Postfach, Switzerland). In vitro dissolution studies were performed to choose the best formulation and selected microparticles were characterized by size and morphology by environmental scanning electron microscopy. Yield and encapsulation efficiency were calculated and in vivo/ex vivo experiments were investigated both of which suggest that selected microparticles can be used for colon targeting of drugs increasing residence time of the drug in the affected area.
    Drug Delivery 02/2015; DOI:10.3109/10717544.2015.1008154
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    ABSTRACT: Abstract Glaucocalyxin A (GLA) is a phytochemical component with multiple pharmacological activities; however, glaucocalyxin A's wider use has been restricted by its poor solubility. In this study, GLA nanosuspensions were prepared with precipitation-combined ultrasonication and were characterized by dynamic light scattering (DLS), transmission electron microscope (TEM), and differential scanning calorimetry (DSC). The GLA nanosuspensions were spherical with a smooth surface and a small size of 143 nm, the drug payload achieved 8.95%, and the maximum GLA concentration reached 1 mg/mL. The lyophilized powders for the GLA nanosuspensions were amorphous and displayed a biphasic drug release pattern with an initial burst release and a consequent sustained release. In contrast to the free drug solution, GLA nanosuspensions showed higher in vitro antitumor activity against HepG2 cells (IC50 value of 1.793 versus 2.884 μg/mL at 24 h, p < 0.01). Meanwhile, nanosuspensions displayed better anticancer efficacy than free GLA on H22 bearing mice (54.11% versus 36.02% tumor inhibition rate). These results indicate that GLA nanosuspensions have great potential for the treatment of hepatic cancer.
    Drug Delivery 02/2015; DOI:10.3109/10717544.2015.1012311
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    ABSTRACT: Abstract The aim of this work was to research the potential functions and the mechanism of absorption of the baicalin (BC)-loaded micelle system that contained Pluronic P123 copolymer (P123) and sodium taurocholate (ST) as carrier materials via oral delivery. Based on the numerous advantages of oral administration, such as cost-effectiveness, flexible and accommodated dosing regimen, and improved compliance for patients, the ST-P123-MMs system would be evaluated as oral delivery vehicle of BC. In this study, X-ray powder diffractometer analysis confirmed the phase change of BC after being incorporated in mixed micelles. The release study in simulated gastric fluid/simulated intestinal fluid exhibited that BC-loaded ST-P123-MMs presented a sustained drug release behavior. Compared with coumarin-6 solution, higher cellar uptake efficiency was achieved for coumarin-6 loaded ST-P123-MMs towards Caco-2 cell lines. The in situ perfusion test in rat indicated that the absorption of BC-loaded ST-P123-MMs in intestinal tract was stronger than BC solution. After oral administration, the Cmax and AUC of BC-loaded ST-P123-MMs were 1.77 times and 1.54 times as high as those of BC suspension in rat, respectively. Promisingly, the formulated BC exhibited a prolonged circulation time with the oral bioavailability increased to 1.54-fold compared with the control group. These results all suggested that P123 and ST mixed micelles could serve as a promising approach to oral administration of BC.
    Drug Delivery 02/2015; DOI:10.3109/10717544.2015.1008705
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    ABSTRACT: Abstract On one hand, the application of anti-microbial peptides (AMPs) in the construction of AMPs-mediated drug delivery system has not yet been fully exploited; on the other hand, its non-selectivity in vivo has also limited its clinical application. In this work, we chose one pH-responsive peptide, [D]-H6L9, and functionalized it onto the surface of liposomes (D-Lip). The protonation of histidines in the sequence of [D]-H6L9 under pH 6.3 could switch the surface charge of D-Lip from negative (under pH 7.4) to positive (under pH 6.3), and the cellular uptake and tumor spheroids uptake were increased accordingly. Lysosome co-localization assay suggested that there was only little overlap of D-Lip with lysosomes in 12 h, which indicated that D-Lip could escape lysosomes effectively. In vivo biodistribution assay on C26 tumor-bearing BALB/C mice showed that DiR-labeled D-Lip could reach tumors as much as PEG-Lip, and both tumor slices and quantitative measurement of dispersed cells of in vivo tumors by flow cytometry demonstrated that D-Lip could be taken up by tumors more efficiently. Therefore, we have established an anti-microbial peptide-mediated liposomal delivery system for tumor delivery.
    Drug Delivery 02/2015; DOI:10.3109/10717544.2014.1003665
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    ABSTRACT: Abstract Current guidelines recommend patients with active and mild-to-moderate ulcerative colitis (UC), who have received initial therapy with 5-aminosalicylic acid (5-ASA). In this study, a novel drug delivery vehicle achieved by pH-sensitive hydrogels was applied to 5-ASA. In our previous work, a novel P(CE-MAA-MEG) pH-sensitive hydrogel was successfully synthesized by the heat-initiated free radical polymerization method. The aim of this study is to investigate its site-specific delivering of drugs to the colon and evaluate its colon-targeting characteristic in vivo. 5-ASA was chosen as a model drug and successfully loaded in the hydrogel. In vitro investigations were carried out to evaluate its release process. Above all, animal treatment results reveal an obvious effect on the UC healing. Therefore, all results suggested that the developed 5-ASA-P(CE-MAA-MEG) hydrogel (5-ASA-GEL) as a colon-targeting vector might have a great potential application in the UC therapy.
    Drug Delivery 02/2015; DOI:10.3109/10717544.2014.996924
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    ABSTRACT: Abstract The conjugation of tunable peptides or materials with nanocarriers represents a promising approach for drug delivery to tumor cells. In this study, we report the development of a novel liposomal carrier system that exploits the cell surface binding synergism between photo-sensitive peptides (PSPs) and targeting ligands. The positive charges of the lysine residues on the cell-penetrating peptides (CPPs) were temporarily caged by the photolabile-protective groups (PG), thereby forming a PSP. Furthermore, this PSP enhances specific uptake into cancer cells after rapidly uncaging the PG via near-infrared (NIR) light illumination. In the circulatory system, the cell penetrability of PSP was hindered. In contrast, the asparagine-glycine-arginine (NGR) peptide moieties, selectively bind to CD13-positive tumors, were attached to the nanocarrier to facilitate the active accumulation of this liposomal carrier in tumor tissue. The dual-modified liposomes (PSP/NGR-L) were prepared by emulsification method, and the concentrations of DSPE-PEG2000-psCPP and DSPE-PEG5000-NGR in the liposomes were chosen to be 4% and 1% (molar ratio), respectively. The mean particle size of the PSP/NGR-L was about 95 nm, and the drug entrapment efficiency was more than 90%. Cellular uptake results demonstrated that the proposed PSP/NGR-L had an enhancement of cancer cell recognition and specific uptake. Furthermore, the PSP/NGR-L demonstrated a stronger antitumor efficacy in the HT-1080 tumor model in nude mice with the aid of NIR illumination.
    Drug Delivery 02/2015; DOI:10.3109/10717544.2015.1008707
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    ABSTRACT: Abstract The clinical success of therapeutic DNA is still hindered due to the lack of effective delivery carriers. Here, we designed a tumor-targeted gene nano delivery system based on EGFR targeting strategy. Epidermal growth factor (EGF) was introduced to nano-complexes of PAMAM dendrimer and DNA via electrostatic interactions to form self-assembled PAMAM/DNA/EGF nano-complexes. The properties of self-assembled complexes were characterized by gel retardation assay and particle size and zeta potential analysis. Meanwhile, the toxicity of EGF-dendriplexes was evaluated by the MTT assay, which indicated that the complexes exhibited decreased cytotoxicity with the incorporation of EGF. We labeled polyamidoamine (PAMAM) dendrimers with FITC or a near-infrared (NIR) dye Lss670 and tested the cellular uptake in vitro and biodistribution in xenograft mouse tumor models. As compared to dendriplexes, the ternary EGF-dendriplexes showed a significantly higher cellular uptake into HepG2 cells due to the specific binding between EGF and EGF receptor (EGFR) over expressed on HepG2 cells, which resulted in the enhanced gene transfection efficiency. The biodistribution of EGF-dendriplexes in vivo was monitored with in vivo imaging technique, which indicated that EGF-dendriplexes enhanced EGFR-positive tumor-targeted biodistribution. These findings indicate that this novel nano-vector realized efficiently tumor-targeting gene delivery and high efficient gene expression in vivo, and it may possess a potential targeting gene delivery system in cancer therapy.
    Drug Delivery 02/2015; DOI:10.3109/10717544.2015.1004381
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    ABSTRACT: Abstract Targeted drug delivery is a method of delivering bioactive compounds to a patient in a manner that increases the therapeutic index. The main goal of a targeted drug delivery system is to prolong, localize, target and have a protected drug interaction with the diseased tissue. Antibody-drug conjugates (ADC) represent an innovative therapeutic application that combines the unique properties of monoclonal antibodies with the potent cell killing activity of cytotoxic bioactive compounds. ADCs are complex molecules composed of an antibody linked, via a stable, chemical, linker with labile bonds, to a biological active cytotoxic (anticancer) payload or drug. The key components of ADC include a monoclonal antibody, a stable linker and a cytotoxic agent to target a variety of cancers. The present mini-review deals with the examination of clinical use and pharmacological properties, as well as the safety of antibody-drug conjugates that are marketed. Ado-trastuzumab emtasine and brenduximab vedotin were examined regarding their mechanism of action, pharmacology, clinical use and safety. These ADCs selectively deliver cargoes to tumor cells and provide clinical benefit by minimizing systemic toxicity.
    Drug Delivery 01/2015; DOI:10.3109/10717544.2014.998323
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    ABSTRACT: Abstract DNA vaccines are simple to produce and can generate strong cellular and humoral immune response, making them attractive vaccine candidates. However, a major shortcoming of DNA vaccines is their poor immunogenicity when administered intramuscularly. Transcutaneous immunization (TCI) via microneedles is a promising alternative delivery route to enhance the vaccination efficacy. A novel dissolving microneedle array (DMA)-based TCI system loaded with cationic liposomes encapsulated with hepatitis B DNA vaccine and adjuvant CpG ODN was developed and characterized. The pGFP expression in mouse skin using DMA was imaged over time. In vivo immunity tests in mice were performed to observe the capability of DMA to induce immune response after delivery of DNA. The results showed that pGFP could be delivered into skin by DMA and expressed in skin. Further, the amount of expressed GFP was likely to peak at day 4. The immunity tests showed that the DMA-based DNA vaccination could induce effective immune response. CpG ODN significantly improved the immune response and achieved the shift of immune type from predominate Th2 type to a balance Th1/Th2 type. The cationic liposomes could further improve the immunogenicity of DNA vaccine. In conclusion, the novel DMA-based TCI system can effectively deliver hepatitis B DNA vaccine into skin, inducing effective immune response and change the immune type by adjuvant CpG ODN.
    Drug Delivery 01/2015; DOI:10.3109/10717544.2014.992497
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    ABSTRACT: Abstract Effects of chitosan oligomers with different types and varying concentrations on the intestinal and pulmonary absorptions of calcitonin were investigated in rats by an in situ closed loop method and an in vivo pulmonary absorption experiment, respectively. Various chitosan oligomers demonstrated different efficiencies in improving the intestinal and pulmonary absorptions of calcitonin, and chitosan hexamer with the optimal concentration of 0.5% (w/v) showed the greatest absorption enhancing effect. Moreover, pharmacodynamic parameters of calcitonin after its coadministration intrapulmonarily with various chitosan oligomers were consistently larger than that in the intestinal delivery, indicating the superior potential of pulmonary administration for systemic delivery of calcitonin. Furthermore, various chitosan oligomers neither obviously increased release amounts of protein nor activities of lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF), revealing the safety of these chitosan oligomers to lung tissue. In addition, bioadhesions of various chitosan oligomers were well consistent with their absorption enhancing effects in the absorption experiment, suggesting the contribution of mucoadhesive properties of chitosan oligomers to their absorption improving effects. Taken together, chitosan oligomers, especially chitosan hexamer, can effectively improve the intestinal and pulmonary absorptions of calcitonin partly due to the mucoadhesion between positive chitosan oligomers and negative mucus in the membrane.
    Drug Delivery 01/2015; DOI:10.3109/10717544.2014.1002946
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    ABSTRACT: Abstract Poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NP) of Val-Val dipeptide monoester prodrugs of ganciclovir (GCV) including L-Val-L-Val-GCV (LLGCV), L-Val-D-Val-GCV (LDGCV) and D-Val-L-Val-GCV (DLGCV) were formulated and dispersed in thermosensitive PLGA-PEG-PLGA polymer gel for the treatment of herpes simplex virus type 1 (HSV-1)-induced viral corneal keratitis. Nanoparticles containing prodrugs of GCV were prepared by a double-emulsion solvent evaporation technique using various PLGA polymers with different drug/polymer ratios. Nanoparticles were characterized with respect to particle size, entrapment efficiency, polydispersity, drug loading, surface morphology, zeta potential and crystallinity. Prodrugs-loaded NP were incorporated into in situ gelling system. These formulations were examined for in vitro release and cytotoxicity. The results of optimized entrapment efficiencies of LLGCV-, LDGCV- and DLGCV-loaded NP are of 38.7 ± 2.0%, 41.8 ± 1.9%, and 45.3 ± 2.2%; drug loadings 3.87 ± 0.20%, 2.79 ± 0.13% and 3.02 ± 0.15%; yield 85.2 ± 3.0%, 86.9 ± 4.6% and 76.9 ± 2.1%; particle sizes 116.6 ± 4.5, 143.0 ± 3.8 and 134.1 ± 5.2 nm; and zeta potential -15.0 ± 4.96, -13.8 ± 5.26 and -13.9 ± 5.14 mV, respectively. Cytotoxicity studies suggested that all the formulations are non-toxic. In vitro release of prodrugs from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when NP were suspended in thermosensitive gels with near zero-order release kinetics. Prodrugs-loaded PLGA NP dispersed in thermosensitive gels can thus serve as a promising drug delivery system for the treatment of anterior eye diseases.
    Drug Delivery 01/2015; DOI:10.3109/10717544.2014.996833