| 1. |
- Björklund, Sebastian, et al.
(författare)
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A water gradient can be used to regulate drug transport across skin
- 2010
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Ingår i: Journal of Controlled Release. - : Elsevier. - 0168-3659 .- 1873-4995. ; 143:2, s. 191-200
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Tidskriftsartikel (refereegranskat)abstract
- At normal conditions there is a substantial water gradient over the skin as it separates the water-rich inside of the body from the dry outside. This leads to a variation in the degree of hydration from the inside to the outside of skin and changes in this gradient may affect its structure and function. In this study we raise the question: How do changes in the water gradient across skin affect its permeability? We approach this problem in novel diffusion experiments that permit strict control of the gradient in the chemical potential of water and hence well-defined boundary conditions. The results demonstrate that a water gradient can be used to regulate transport of drugs with different lipophilic characteristics across the skin barrier. It is shown that the transport of metronidazole (log Po/w=0.0) and methyl salicylate (log Po/w=2.5) across skin increases abruptly at low water gradients, corresponding to high degrees of skin hydration, and that this effect is reversible. This phenomenon is highly relevant to drug delivery applications due to its potential of temporarily open the skin barrier for transdermal drug delivery and subsequently close the barrier after treatment. Further, the results contribute to the understanding of the occlusion effect and indicate the boundary conditions of the water gradient needed to make use of this effect
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| 2. |
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| 3. |
- Ezzat, Kariem, et al.
(författare)
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Solid formulation of cell-penetrating peptide nanoparticles with siRNA and their stability in simulated gastric conditions
- 2012
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 162:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Cell-penetrating peptides (CPPs) are short cationic peptides that have been extensively studied as drug delivery vehicles for proteins, nucleic acids and nanoparticles. However, the formulation of CPP-based therapeutics into different pharmaceutical formulations and their stability in relevant biological environments have not been given the same attention. Here, we show that a newly developed CPP, PepFect 14 (PF14), forms non-covalent nanocomplexes with short interfering RNA (siRNA), which are able to elicit efficient RNA-interference (RNAi) response in different cell-lines. RNAi effect was obtained at low siRNA doses with a unique kinetic profile. Furthermore, we utilized the solid dispersion technique to formulate PF14/siRNA nanocomplexes into solid formulations that were as active as the freshly prepared nanocomplexes in solution. Importantly, the freshly prepared nanocomplexes and solid formulations were stable after incubation with simulated gastric fluid having a pH of 1.2 and containing proteolytic enzymes. These results demonstrate the activity of PF14 in delivering and protecting siRNA in different pharmaceutical forms and biological environments.
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| 4. |
- Fredenberg, Susanne, et al.
(författare)
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Pore formation and pore closure in Poly(D,L-lactide-co-glycolide) films.
- 2011
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 1873-4995 .- 0168-3659. ; 150, s. 142-149
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Tidskriftsartikel (refereegranskat)abstract
- Pore formation and pore closure in poly(D,L-lactide-co-glycolide)-based drug delivery systems are two important processes as they control the release of the encapsulated drug. The phenomenon pore closure was investigated by studying the effects of the pH and the temperature of the release medium, and the properties of the polymer. Poly(D,L-lactide-co-glycolide) (PLG) films were subjected to a pore forming pre-treatment, and then pore closure was observed simultaneously with changes in glass transition temperature, wettability (contact angle), water absorption and mass remaining. To further understand the effect of pH, combined pore formation and pore closure were studied at different pH values. Pore closure was increased in a release medium with low pH, with a low-molecular-weight PLG of relatively low degree of hydrophobicity, or at high temperature. Pore closure occurred by two different mechanisms, one based on polymer-polymer interactions and one on polymer-water interactions. The mobility of the PLG chains also played an important role. The surface of the PLG films were more porous at pH 5-6 than at lower or higher pH, as pore formation was relatively fast and pore closure were less pronounced in this pH range. The pH had a significant impact on the porous structure, which should be kept in mind when evaluating experimental results, as the pH may be significantly decreased in vitro, in vivo and in situ. The results also show that the initial porosity is very important when using a high-molecular-weight PLG.
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| 5. |
- Hassane, Fatouma Said, et al.
(författare)
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Insights into the cellular trafficking of splice redirecting oligonucleotides complexed with chemically modified cell-penetrating peptides
- 2011
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 153:2, s. 163-172
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Tidskriftsartikel (refereegranskat)abstract
- Conjugates of cell-penetrating peptides (CPP) and splice redirecting oligonucleotides (ON) display clinical potential as attested by in vivo experimentation in murine models of Duchenne muscular dystrophy. However, micromolar concentrations of these conjugates are required to obtain biologically relevant responses as a consequence of extensive endosomal sequestration following endocytosis. Recent work from our group has demonstrated that appending stearic acid to CPPs increases their efficiency and that the inclusion of pH titrable entities leads to further improvement. Moreover, these modified CPPs form non covalent complexes with charged ON analogs or siRNAs, which allows decreasing the concentrations of ONs by nearly one log. These modified CPPs and the parent peptides have been compared here in the same in vitro model in terms of cell uptake, trafficking and splicing redirection activity. The increased splicing redirection activity of our modified CPPs cannot be explained by differences in cell uptake but rather by their enhanced ability to escape from endocytic vesicles. Accordingly, a clear correlation between membrane destabilizing activity and splicing redirection was observed using a liposome leakage assay. Studies of cellular trafficking for the most active PF6:ON complexes indicate uptake by clathrin-mediated endocytosis using either FACS cell uptake or a splicing redirection functional assay. Acidification of intracellular vesicles and membrane potential were found important for splicing redirection but not for cell uptake. These results do confirm that the increased potency of PF6:ON complexes is not due to the use of a non endocytic route of cell internalization as proposed for some CPPs.
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| 6. |
- Hsiao, Meng-Hsuan, et al.
(författare)
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Design and characterization of a novel amphiphilic chitosan nanocapsule-based thermo-gelling biogel with sustained in vivo release of the hydrophilic anti-epilepsy drug ethosuximide
- 2012
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 161:3, s. 942-948
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Tidskriftsartikel (refereegranskat)abstract
- Thermo-gelling injectable nanogels, with no burst release of loaded drug, were prepared by a simple route by combining self assembled nanocapsules of amphiphilically modified chitosan with glycerophosphate di-sodium salt and glycerol. The potential as a depot drug delivery system was demonstrated in vivo through the therapeutic effect of ethosuximide (ESM) loaded nanogels, suppressing spike wave discharges (SWDs) in Long Evan rat model. Simultaneously clearance of gels from the site of administration was monitored non-invasively using MRI. The gel structure was characterized using TEM and SEM, confirming the gels to be an assembly of nanocapsules and using two-photon microscopy to visualize the network structure. In vitro drug release studies using ESM revealed that the nanogels exhibited extended, mostly Fickian release. Finally, all investigated formulations displayed excellent cytotoxicity data determined by MTT assay using human retinal pigmented epithelium cells. All presented properties are highly desirable for injectable depot gels for drug delivery.
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| 7. |
- Jämstorp, Erik, et al.
(författare)
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Mechanically strong geopolymers offer new possibilities in treatment of chronic pain
- 2010
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 146:3, s. 370-377
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Tidskriftsartikel (refereegranskat)abstract
- We propose that a clay derived class of materials, known as geopolymers, may solve the problem of finding materials for controlled release with the right combination of properties necessary for a safe and sustained oral delivery of highly potent opioids. We show that the opioid Fentanyl, and its structurally similar sedative Zolpidem, can be embedded into metakaolin based geopolymer pellets to provide prolonged release dosage forms with mechanical strengths of the same order of magnitude as that of human teeth. The results presented in the current work may open up new opportunities for future development of drug delivery for high potency drugs employing high-strength and variable-pore-structure geopolymers and materials alike.
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| 8. |
- Kaunisto, Erik, et al.
(författare)
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A mechanistic modelling approach to polymer dissolution using magnetic resonance microimaging
- 2010
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 147:2, s. 232-241
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Tidskriftsartikel (refereegranskat)abstract
- In this paper a computationally efficient mathematical model describing the swelling and dissolution of a polyethylene oxide tablet is presented. The model was calibrated against polymer release, front position and water concentration profile data inside the gel layer, using two different diffusion models. The water concentration profiles were obtained from magnetic resonance microimaging data which, in addition to the previously used texture analysis method, can help to validate and discriminate between the mechanisms of swelling, diffusion and erosion in relation to the dissolution process. Critical parameters were identified through a comprehensive sensitivity analysis, and the effect of hydrodynamic shearing was investigated by using two different stirring rates. Good agreement was obtained between the experimental results and the model. (C) 2010 Elsevier B.V. All rights reserved.
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| 9. |
- Kisiel, Marta, et al.
(författare)
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Critical assessment of rhBMP-2 mediated bone induction : An in vitro and in vivo evaluation.
- 2012
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 162:3, s. 646-653
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the influence of formulation and storage conditions on rhBMP-2 bioactivity is extremely important for its clinical application. Reports in the literature show that different research groups employ different parameters such as formulation conditions, storage, doses for in vivo applications etc. that makes it difficult to correlate results from different experiments. We therefore decided to rationalize these anomalies by performing a basic study on such parameters using two commercially available BMPs. Our in vitro experiments suggest that BMPs from different sources have significant differences in their bioactivity. The clinically approved rhBMP-2 (InductOs®; BMP-P) showed superior stability, compared to rhBMP-2 from R&D Systems (BMP-R) at physiological pH (determined by ALP assay). This BMP-P also showed lower binding to polypropylene Eppendorf tube. The BMP-R almost lost its bioactivity within 30min at physiological pH and also shows more adhesion to plastic surfaces. This aggregation behavior was unequivocally ascertained by performing light scattering studies of the two BMPs, which revealed linear aggregation with time for BMP-R unlike BMP-P. The in vitro results were also reflected in the in vivo experiments, in a rat ectopic model with injectable hyaluronic acid (HA) hydrogel as BMP carrier. After 7weeks post-implantation we observed larger bone volume with oriented collagen in the BMP-P group but a smaller bone with disoriented collagen in the BMP-R case. Our results highlight the large difference in activity between seemingly identical substances and also the importance of proper handling of such sensitive proteins.
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| 10. |
- Lehto, Taavi, et al.
(författare)
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Delivery of nucleic acids with a stearylated (RxR)4 peptide using a non-covalent co-incubation strategy
- 2010
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 141:1, s. 42-51
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, oligonucleotide-based molecules have been intensely used to modulate gene expression. All these molecules share the common feature of being essentially impermeable over cellular membranes and they therefore require efficient delivery vectors. Cell-penetrating peptides are a group of delivery peptides that has been readily used for nucleic acid delivery. In particular, polyarginine and derivates thereof, i.e. the (RxR)4 peptide, have been applied with success both in vitro and in vivo. A major problem, however, with these arginine-rich peptides is that they frequently remain trapped in endosomal compartments following internalization. The activity of polyarginine has previously been improved by conjugation to a stearyl moiety. Therefore, we sought to investigate what impact such modification would have on the pre-clinically used (RxR)4 peptide for non-covalent delivery of plasmids and splice-correcting oligonucleotides (SCOs) and compare it with stearylated Arg9 and Lipofectamine™ 2000. We show that stearyl-(RxR)4 mediates efficient plasmid transfections in several cell lines and the expression levels are significantly higher than when using unmodified (RxR)4 or stearylated Arg9. Although the transfection efficiency is lower than with Lipofectamine™ 2000, we show that stearyl-(RxR)4 is substantially less toxic. Furthermore, using a functional splice-correction assay, we show that stearyl-(RxR)4 complexed with 2′-OMe SCOs promotes significant splice correction whereas stearyl-Arg9 fails to do so. Moreover, stearyl-(RxR)4 promotes dose-dependent splice correction in parity with (RxR)4-PMO covalent conjugates, but at least 10-times lower concentration. These features make this stearic acid modified analog of (RxR)4 an intriguing vector for future in vivo experiments.
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| 11. |
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| 12. |
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| 13. |
- Martinez-Sanz, Elena, et al.
(författare)
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Bone reservoir : Injectable hyaluronic acid hydrogel for minimal invasive bone augmentation
- 2011
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 152:2, s. 232-240
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Tidskriftsartikel (refereegranskat)abstract
- A strategy has been designed to develop hyaluronic acid (HA) hydrogel for in vivo bone augmentation using minimal invasive technique. A mild synthetic procedure was developed to prepare aldehyde modified HA by incorporating an amino-glycerol side chain via amidation reaction and selective oxidation of the pendent group. This modification, upon mixing with hydrazide modified HA formed hydrazone-crosslinked hydrogel within 30 s that was stable at physiological pH. In vitro experiments showed no cytotoxicity of hydrogel with the controlled release of active bone morphogenic protein-2 (BMP-2). In vivo evaluation of this gel as a BMP-2 carrier was performed by injecting gels over the rat calvarium and showed bone formation in 8 weeks in correlation with the amount of BMP-2 loaded (0, 1 and 30 pig) within the gel. Furthermore, hydrogels with 30 Kg of BMP-2 induced less bone formation upon subcutaneous injection in comparison with subperiosteal implantation. Histological examination showed newly formed bone with a high expression of osteocalcin, osteopontin and with angiogenic bone marrow when higher BMP-2 concentration was employed. Our result suggests that novel HA hydrogels could be used as a BMP-2 carrier and can promote bone augmentation for potential orthopedic applications.
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| 14. |
- Marucci, Mariagrazia, et al.
(författare)
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Osmotic pumping release from ethyl-hydroxypropyl-cellulose-coated pellets: A new mechanistic model.
- 2010
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 1873-4995 .- 0168-3659. ; 142, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- A new mechanistic model of drug release by osmotic pumping and diffusion from pellets coated with a semipermeable film developing pores created by the leaching of water-soluble compounds initially present in the coating, has been developed. The model describes dynamically all the main processes occurring during release, i.e. the inflow of solvent driven by the difference in osmotic pressure across the coating film, dissolution of the drug, swelling of the pellet due to mass accumulation, the build-up of hydrostatic pressure inside the pellet, and the outflow of the dissolved drug through the pores. The model was validated by comparison with the release profile of single metoprolol succinate pellets coated with a film made of ethyl cellulose and hydroxypropyl cellulose (80:20). This system was chosen as it was shown that the release mechanism was osmotic pumping, and that the release occurred through small pores created in the coating by hydroxypropyl cellulose leaching. Insight into the release process was obtained via dose release experiments performed at different osmotic pressures of the release medium, single-pellet release experiments, and a study of the coating before and after immersion in the release medium using scanning electron microscopy. The good agreement found between the predicted release and the experimental data confirmed the validity of the model and its prediction capacity. The model can be used to calculate important variables, e.g. the drug concentration profile in a pore and the pressure build-up inside the pellet.
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| 15. |
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| 16. |
- Pae, Janely, et al.
(författare)
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Translocation of cell-penetrating peptides across the plasma membrane is controlled by cholesterol and microenvironment created by membranous proteins
- 2014
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 192, s. 103-113
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Tidskriftsartikel (refereegranskat)abstract
- Despite the extensive research in the field of CPPs' cell entry the exact mechanisms underlying their cellular uptake and the role of involved cell surface molecules in the internalization process have remained controversial. The present study focused on the interactions between CPPs and plasma membrane compounds using giant plasma membrane vesicles (GPMVs). GPMVs have shown to be a suitable model to study the translocation of CPPs across the plasma membrane in conditions lacking endocytosis. Our results show that higher cholesterol content and tighter packing of membrane predominantly reduce the accumulation of transportan, TP10 and model amphipathic peptide (MAP) in vesicles, indicating that the internalization of CPPs takes place preferentially via the more dynamic membrane regions. The partial digestion of membrane proteins from GPMVs' surface, on the other hand, drastically reduced the accumulation of nona-arginine and Tat peptide into vesicles, suggesting that proteins play a crucial role in the uptake of arginine-rich CPPs.
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| 17. |
- Pappinen, S., et al.
(författare)
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Organotypic cell cultures and two-photon imaging: Tools for in vitro and in vivo assessment of percutaneous drug delivery and skin toxicity
- 2012
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659. ; 161:2, s. 656-667
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Tidskriftsartikel (refereegranskat)abstract
- The outermost protective layer of the skin, the stratum corneum, is responsible for skin impermeability toward external medications and potentially harmful chemicals. Stratum corneum is the target for physical and chemical approaches to enhance drug permeation. These approaches are commonly investigated in the field of drug delivery, but the drug absorption enhancement is often linked with local toxicity. In this review we are discussing two emerging technologies for drug and chemical studies in the skin: organotypic cell cultures and non-invasive two-photon microscopic imaging. Even though several cell culture based 'skin equivalents' have been introduced and validated for skin irritation testing, they are usually leaky and inadequately characterized in terms of permeation. Rat epidermal culture model (ROC) has been thoroughly characterized and it shows comparable barrier properties with the human skin thereby being useful in drug permeation and toxicity studies. In vitro and in vivo visualizations of permeants and skin structures are now feasible due to the rapid development of two-photon microscopy that allows improved depth scanning and direct in vivo visualization of the permeating compounds and adverse reactions in the skin structures. In summary, the new tools in percutaneous drug delivery studies will provide new insights to the permeation process and local toxicity. These tools may facilitate development of effective and safe transdermal drug delivery methods. (c) 2012 Elsevier B.V. All rights reserved.
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| 18. |
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| 19. |
- Poelstra, K, et al.
(författare)
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Drug targeting to the diseased liver
- 2012
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Ingår i: Journal of controlled release : official journal of the Controlled Release Society. - : Elsevier BV. - 1873-4995. ; 161:2, s. 188-197
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Tidskriftsartikel (refereegranskat)
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| 20. |
- Saalik, Pille, et al.
(författare)
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Penetration without cells : Membrane translocation of cell-penetrating peptides in the model giant plasma membrane vesicles
- 2011
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 153:2, s. 117-125
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Tidskriftsartikel (refereegranskat)abstract
- The cellular internalization of cell-penetrating peptides (CPPs) is proposed to take place by both endocytic processes and by a direct translocation across the plasma membrane. So far only scarce data is available about what determines the choice between the two uptake routes, or the proportion of used pathways when both are active simultaneously. Furthermore, the mechanism(s) of membrane penetration by peptides is itself still a matter of debate. We have introduced the giant plasma membrane vesicles (GPNIVs) to study the interaction of six well-described CPPs (fluorescently labeled nona-arginine, Tat peptide, Penetratin, MAP, Transportan and TP10) in a model system of native plasma membrane without the interference of endocytic processes. The membranes of GPMVs are shown to segregate into liquid-ordered and liquid-disordered phases at low temperatures and we demonstrate here by confocal microscopy that amphipathic CPPs preferentially associate with liquid-disordered membrane areas. Moreover, all tested CPPs accumulate into the lumen of GPMVs both at ambient and low temperature. The uncharged control peptide and dextran, in contrary, do not translocate from the medium into the lumen of vesicles. The absence of energy-dependent cellular processes and the impermeability to hydrophilic macromolecules makes the GPMVs a useful model to study the translocation of CPPs across the plasma membrane in conditions lacking endocyrosis.
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| 21. |
- Thomas, Anitha M., et al.
(författare)
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Development of a liposomal nanoparticle formulation of 5-Fluorouracil for parenteral administration : Formulation design, pharmacokinetics and efficacy
- 2011
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 150:2, s. 212-219
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Tidskriftsartikel (refereegranskat)abstract
- 5-Fluorouracil (5-FU) is a small, very membrane permeable drug that is poorly retained within the aqueous compartment of liposomal nanoparticles (LNP). To address this problem a novel method relying on formation of a ternary complex comprising copper, low molecular weight polyethylenimine (PEI) and 5-FU has been developed. More specifically, in the presence of entrapped copper and PEI, externally added 5-FU can be efficiently encapsulated (>95%) in DSPC/Chol (1,2-Distearoyl-sn-Glycero-3-Phosphocholine/cholesterol; 55:45mol%) liposomes (130-170nm) to achieve drug-to-lipid ratios of 0.1 (mol:mol). Drug release studies completed using this LNP formulation of 5-FU demonstrated significant improvements in drug retention in vitro and in vivo. Plasma concentrations of 5-FU were 7- to 23-fold higher when the drug was administered intravenously to mice as the LNP 5-FU formulation compared to free 5-FU. Further, the therapeutic effects of the LNP 5-FU formulation, as determined in a HT-29 subcutaneous colorectal cancer model where treatment was given QDx5, was greater than that which could be achieved with free 5-FU when compared at equivalent doses. This is the first time an active loading method has been described for 5-FU. The use of ternary metal complexation strategy to encapsulate therapeutic agents may define a unique platform for preparation of LNP drug formulations.
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| 22. |
- Wing Cheung, Mak, et al.
(författare)
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Triggering of drug relase of particles in hair follicles
- 2012
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Ingår i: Journal of Controlled Release. - : Elsevier. - 0168-3659 .- 1873-4995. ; 160, s. 509-514
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Tidskriftsartikel (refereegranskat)abstract
- Particulate drug delivery via hair follicles represents a promising concept, although requirements are high. This process must be realized at the desired depth and at the appropriate time, due to the fact that the particles themselves are not able to overcome the follicular skin barrier.In the present study, a novel triggering concept for the release of a model drug from the delivering particles is presented based on the application of two different particle types of the same size, where one particle type is the drug carrier, and the second one is loaded with a protease. The latter particle type is supposed to interact with the drug-carrying particles to trigger the drug release. A mixture of both particles was applied onto porcine skin samples, followed by follicular analysis. As a control, the particles were applied unaided without protease, whereas one skin area remained untreated. The investigations revealed that the protease was able to release the model drug from the delivering particles in significant depths within the hair follicle (866 ± 62 nm). Additionally, an uptake of the model drug in the sebaceous gland was observed after release providing a promising novel approach for the development of treatment strategies for different skin diseases.
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| 23. |
- Zetterberg, Malin M., et al.
(författare)
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PEG-stabilized lipid disks as carriers for amphiphilic antimicrobial peptides
- 2011
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 156:3, s. 323-328
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial peptides hold potential as a possible alternative, or complement, to conventional antibiotics but new, safe and efficient means are needed for formulation and administration of the peptides. In this study we have investigated the utility of a novel type of lipid particles, the polyethylene glycol-stabilized lipid-disks, as carriers for the model peptide melittin. The structural integrity of the carrier particle when loaded with the peptide was investigated using cryo-transmission electron microscopy. Liposome leakage upon addition of the peptide-lipid-disks was monitored as a means to verify the membrane lytic effect of the formulation. The susceptibility of melittin to tryptic digestion was studied and compared in the absence and presence of lipid-disks. Finally, the antibacterial effect of the peptide-lipid-disk formulation was compared to that of free melittin after both single and repeated exposure to Escherichia coli. The results show that melittin can redistribute from the disk into a new host membrane and that formulation in the disks does not compromise melittin's membrane permeabilizing ability. Further, the peptide was found to be fully protected against degradation when bound to the disks. Time-kill experiments revealed that all the antibacterial effect of melittin administered in free form was gone after a single exposure to E. coli. In contrast, the disk formulation showed significant cell-killing effect also upon a second exposure to bacteria, indicating an extended release of peptide from the lipid-disks. These results suggest that the lipid-disks constitute a new class of promising carriers for peptide antibiotics.
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