Change search
Link to record
Permanent link

Direct link
Publications (10 of 10) Show all publications
Simoni, E., Valente, F., Boge, L., Eriksson, M., Gentilin, E., Candito, M., . . . Astolfi, L. (2019). Biocompatibility of glycerol monooleate nanoparticles as tested on inner ear cells. International Journal of Pharmaceutics, 572, Article ID 118788.
Open this publication in new window or tab >>Biocompatibility of glycerol monooleate nanoparticles as tested on inner ear cells
Show others...
2019 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 572, article id 118788Article in journal (Refereed) Published
Abstract [en]

Sensorineural hearing loss due to aging, noise exposure, trauma or drug ototoxicity is irreversible because cochlear hair cells and neurons cannot regenerate. Recently, therapeutic strategies involving nanoparticles have been developed as innovative drug delivery systems. Thermodynamically stable liquid crystalline nanoparticles based on the polar lipid glycerol monooleate (GMO NP, cubosomes), nontoxic and able to encapsulate both hydrophilic and hydrophobic compounds, were produced and tested for biocompatibility in an immortalized Organ of Corti derived cell line (OC-k3), through cell viability and cytomorphological assays, and Western blot expression profiles of apoptotic markers. Overall, the GMO NP were biocompatible in OC-k3 at the doses and time tested, supporting previous data obtained in a neuronal cell line (PC12). The results encourage further tests on GMO NP-mediated drug release with improved target specificity and could be useful to develop innovative therapies against sensorineural hearing loss.

Place, publisher, year, edition, pages
Elsevier B.V., 2019
Keywords
Apoptosis, Cell cycle, Cubosome, OC-k3 cells, Toxicity
National Category
Natural Sciences
Identifiers
urn:nbn:se:ri:diva-40932 (URN)10.1016/j.ijpharm.2019.118788 (DOI)2-s2.0-85075399346 (Scopus ID)
Note

Funding details: Prat-CPDA110048; Funding details: Ministero dell’Istruzione, dell’Università e della Ricerca, MIUR, PRIN-2010S58B38_004; Funding text 1: This work was supported by the Italian Ministry of Education, University and Research (MIUR) , Italy [grant n. PRIN-2010S58B38_004 ] and the University of Padua (grant n. Prat-CPDA110048 ).

Available from: 2019-12-10 Created: 2019-12-10 Last updated: 2020-06-04Bibliographically approved
Håkansson, J., Ringstad, L., Umerska, A., Johansson, J., Andersson, T., Boge, L., . . . Mahlapuu, M. (2019). Characterization of the in vitro, ex vivo, and in vivo Efficacy of the Antimicrobial Peptide DPK-060 Used for Topical Treatment. Frontiers in Cellular and Infection Microbiology, 9, Article ID 174.
Open this publication in new window or tab >>Characterization of the in vitro, ex vivo, and in vivo Efficacy of the Antimicrobial Peptide DPK-060 Used for Topical Treatment
Show others...
2019 (English)In: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 9, article id 174Article in journal (Refereed) Published
Abstract [en]

Antimicrobial peptides, also known as host defense peptides, have recently emerged as a promising new category of therapeutic agents for the treatment of infectious diseases. This study evaluated the preclinical in vitro, ex vivo, and in vivo antimicrobial activity, as well as the potential to cause skin irritation, of human kininogen-derived antimicrobial peptide DPK-060 in different formulations designed for topical delivery. We found that DPK-060 formulated in acetate buffer or poloxamer gel caused a marked reduction of bacterial counts of Staphylococcus aureus in vitro (minimum microbicidal concentration <5 μg/ml). We also found that DPK-060 in poloxamer gel significantly suppressed microbial survival in an ex vivo wound infection model using pig skin and in an in vivo mouse model of surgical site infection (≥99 or ≥94% reduction in bacterial counts was achieved with 1% DPK-060 at 4 h post-treatment, respectively). Encapsulation of DPK-060 in different types of lipid nanocapsules or cubosomes did not improve the bactericidal potential of the peptide under the applied test conditions. No reduction in cell viability was observed in response to administration of DPK-060 in any of the formulations tested. In conclusion, the present study confirms that DPK-060 has the potential to be an effective and safe drug candidate for the topical treatment of microbial infections; however, adsorption of the peptide to nanocarriers failed to show any additional benefits.

Keywords
DPK-060, antimicrobial peptides, cubosomes, lipid nanocapsules, skin infections
National Category
Natural Sciences
Identifiers
urn:nbn:se:ri:diva-39066 (URN)10.3389/fcimb.2019.00174 (DOI)31192163 (PubMedID)2-s2.0-85068146000 (Scopus ID)
Available from: 2019-06-26 Created: 2019-06-26 Last updated: 2024-07-01Bibliographically approved
Boge, L., Hallstensson, K., Ringstad, L., Johansson, J., Andersson, T., Davoudi, M., . . . Andersson, M. (2019). Cubosomes for topical delivery of the antimicrobial peptide LL-37. European journal of pharmaceutics and biopharmaceutics, 134, 60-67
Open this publication in new window or tab >>Cubosomes for topical delivery of the antimicrobial peptide LL-37
Show others...
2019 (English)In: European journal of pharmaceutics and biopharmaceutics, ISSN 0939-6411, E-ISSN 1873-3441, Vol. 134, p. 60-67Article in journal (Refereed) Published
Abstract [en]

In this study, the use of cubosomes for topical delivery of the antimicrobial peptide (AMP) LL-37 was investigated. Topical delivery of AMPs is of great interest for treatment of skin infections caused by bacteria, such as Staphylococcus aureus. AMP containing cubosomes were produced by three different preparation protocols and compared: (i) pre-loading, where LL-37 was incorporated into a liquid crystalline gel, which thereafter was dispersed into nanoparticles, (ii) post-loading, where LL-37 was let to adsorb onto pre-formed cubosomes, and (iii) hydrotrope-loading, where LL-37 was incorporated during the spontaneously formed cubosomes in an ethanol/glycerol monooleate mixture. Particle size and size distribution were analyzed using dynamic light scattering (DLS), liquid crystalline structure by small angle x-ray scattering (SAXS) and release of LL-37 by a fluorescamine assay. Proteolytic protection of LL-37 as well as bactericidal effect after enzyme exposure was investigated. The skin irritation potential of cubosomes was examined by an in vitro epidermis model. Finally, the bacterial killing property of the cubosomes was examined by an ex vivo pig skin wound infection model with Staphylococcus aureus. Data showed that a high loading of LL-37 induced formation of vesicles in case of cubosomes prepared by sonication (pre-loading). No release of LL-37 was observed from the cubosomes, indicating strong association of the peptide to the particles. Proteolysis studies showed that LL-37 was fully protected against enzymatic attacks while associated with the cubosomes, also denoting strong association of the peptide to the particles. As a consequence, bactericidal effect after enzyme exposure remained, compared to pure LL-37 which was subjected to proteolysis. No skin irritation potential of the cubosomes was found, thus enabling for topical administration. The ex vivo wound infection model showed that LL-37 in pre-loaded cubosomes killed bacteria most efficient.

Keywords
alcohol, cathelicidin antimicrobial peptide LL 37, cubosome, drug carrier, fluorescamine, glycerol oleate, hydrotrope, nanoparticle, unclassified drug
National Category
Chemical Sciences
Identifiers
urn:nbn:se:ri:diva-37674 (URN)10.1016/j.ejpb.2018.11.009 (DOI)30445164 (PubMedID)2-s2.0-85056876558 (Scopus ID)
Available from: 2019-01-29 Created: 2019-01-29 Last updated: 2024-07-01Bibliographically approved
Boge, L., Browning, K., Nordström, R., Campana, M., Damgaard, L., Seth Caous, J., . . . Andersson, M. (2019). Peptide-Loaded Cubosomes Functioning as an Antimicrobial Unit against Escherichia coli. ACS Applied Materials and Interfaces, 11(24), 21314-21322
Open this publication in new window or tab >>Peptide-Loaded Cubosomes Functioning as an Antimicrobial Unit against Escherichia coli
Show others...
2019 (English)In: ACS Applied Materials and Interfaces, ISSN 1944-8244, E-ISSN 1944-8252, Vol. 11, no 24, p. 21314-21322Article in journal (Refereed) Published
Abstract [en]

Dispersions of cubic liquid crystalline phases, also known as cubosomes, have shown great promise as delivery vehicles for a wide range of medicines. Due to their ordered structure, comprising alternating hydrophilic and hydrophobic domains, cubosomes possess unique delivery properties and compatibility with both water-soluble and -insoluble drugs. However, the drug delivery mechanism and cubosome interaction with human cells and bacteria are still poorly understood. Herein, we reveal how cubosomes loaded with the human cathelicidin antimicrobial peptide LL-37, a system with high bacteria-killing effect, interact with the bacterial membrane and provide new insights into the eradication mechanism. Combining the advanced experimental techniques neutron reflectivity and quartz crystal microbalance with dissipation monitoring, a mechanistic drug delivery model for LL-37-loaded cubosomes on bacterial mimicking bilayers was constructed. Moreover, the cubosome interaction with Escherichia coli was directly visualized using super-resolution laser scanning microscopy and cryogenic electron tomography. We could conclude that cubosomes loaded with LL-37 adsorbed and distorted bacterial membranes, providing evidence that the peptide-loaded cubosomes function as an antimicrobial unit.

Place, publisher, year, edition, pages
American Chemical Society, 2019
Keywords
antimicrobial peptide, bacteria, cubosome, LL-37, membrane, Controlled drug delivery, Electric impedance tomography, Escherichia coli, Membranes, Peptides, Targeted drug delivery, Cubosomes, Experimental techniques, Hydrophilic and hydrophobic, Laser scanning microscopy, Liquid-crystalline phasis, Quartz crystal microbalance with dissipation monitoring, Drug interactions
National Category
Natural Sciences
Identifiers
urn:nbn:se:ri:diva-39268 (URN)10.1021/acsami.9b01826 (DOI)2-s2.0-85067578230 (Scopus ID)
Note

Funding details: MAX4ESSFUN, 2016-11-01, CTH-009; Funding details: 604182; Funding text 1: The authors thank Carolina Tangemö at the Centre for Cellular Imaging (CCI, University of Gothenburg, Sweden), Camilla Holmlund at Umeå core facility for electron microscopy (Umeå University, Sweden), and the National Microscopy Infrastructure, NMI (VR-RFI 2016-00968) for providing assistance in high-resolution confocal and cryogenic electron microscopy imaging. ISIS Neutron and Muon Source, Rutherford Appleton Laboratory, Didcot, U.K. (RB number: 1810031 DOI:10.5286/ISIS.E.92922658) is acknowledged for beamtime allocation from the Science and Technology Facilities Council. Adrian Rennie (Uppsala University, Sweden) is greatly acknowledged for fruitful discussions about NR data. Financial support was obtained from the European Union’s Seventh Framework Program grant agreement No. 604182 within the FORMAMP project (L.B and L.R. and R.N.) and from RISE Research Institutes of Sweden (Stockholm, Sweden) (L.B., L.R., M.H., and J.S.-C.). Financial support is also acknowledged from the LEO Foundation Center for Cutaneous Drug Delivery (grant number 2016-11-01; K.L.B. and L.S.E.D.) and MAX4ESSFUN (grant number CTH-009; L.B., K.L.B., and M.A.).

Available from: 2019-07-03 Created: 2019-07-03 Last updated: 2024-04-29Bibliographically approved
Valente, F., Bysell, H., Simoni, E., Boge, L., Eriksson, M., Martini, A. & Astolfi, L. (2018). Evaluation of toxicity of glycerol monooleate nanoparticles on PC12 cell line.. International Journal of Pharmaceutics, 539(1-2), 23-30, Article ID S0378-5173(18)30054-1.
Open this publication in new window or tab >>Evaluation of toxicity of glycerol monooleate nanoparticles on PC12 cell line.
Show others...
2018 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 539, no 1-2, p. 23-30, article id S0378-5173(18)30054-1Article in journal (Refereed) Published
Abstract [en]

An innovative approach to improve drug delivery is the use of glycerol monooleate nanoparticles. Numerous studies describe their high versatility, low toxicity and ability to carry relatively high loads of conjugated compounds including scarcely soluble ones, providing sustained drug release and increasing drug diffusion and half-life. Despite a growing interest in their potential use for therapeutic applications, there are surprisingly few literature data concerning the toxic effects of these nanoparticles at high concentrations in vitro and in vivo, and their effects on cell metabolism. We produced and characterized from a physical-chemical point of view glycerol monooleate nanoparticles and tested them on the PC12 cell line, a rat model of neuronal differentiation. The toxicity of these nanoparticles was evaluated by molecular methods on cell viability, cell cycle, nanoparticle uptake and induction of apoptosis. The results showed that glycerol monooleate nanoparticles up to 100 μg/mL had no toxic effects on PC12 cells, did not induce significant changes in the cell cycle nor cause apoptosis. The nanoparticles entered PC12 cells 8 h after treatment, successfully delivering the conjugate compound inside cells. Overall, glycerol monooleate nanoparticles did not exhibit significant toxicity on PC12 cell line in concentrations up to 100 µg/mL, supporting their therapeutic use as drug delivery systems.

Keywords
Apoptosis, Nanoparticle, PC12 cell line, Toxicity
National Category
Natural Sciences
Identifiers
urn:nbn:se:ri:diva-33340 (URN)10.1016/j.ijpharm.2018.01.035 (DOI)29366940 (PubMedID)2-s2.0-85041522082 (Scopus ID)
Available from: 2018-02-28 Created: 2018-02-28 Last updated: 2020-01-16Bibliographically approved
Boge, L., Västberg, A., Umerska, A., Bysell, H., Eriksson, J., Edwards, K., . . . Andersson, M. (2018). Freeze-dried and re-hydrated liquid crystalline nanoparticles stabilized with disaccharides for drug-delivery of the plectasin derivative AP114 antimicrobial peptide. Journal of Colloid and Interface Science, 522, 126-135
Open this publication in new window or tab >>Freeze-dried and re-hydrated liquid crystalline nanoparticles stabilized with disaccharides for drug-delivery of the plectasin derivative AP114 antimicrobial peptide
Show others...
2018 (English)In: Journal of Colloid and Interface Science, ISSN 0021-9797, E-ISSN 1095-7103, Vol. 522, p. 126-135Article in journal (Refereed) Published
Abstract [en]

Liquid crystalline nanoparticles (LCNPs), e.g. cubosomes and hexosomes, are receiving more and more attraction as drug delivery vehicles. Dry powder formulation that forms LCNPs upon hydration can be advantageous to make new routes of administration accessible. In this work, we investigate use of three disaccharides (lactose, trehalose and sucrose) as protective matrices for glycerol monooleate based LCNP forming powders produced by freeze-drying. Phase behavior, particle size and size distributions at the different preparation steps were monitored by small angle x-ray scattering (SAXS) and dynamic light scattering (DLS). Particle appearance was imaged by cryogenic transmission electron microscopy (cryo-TEM). Moreover, the therapeutic relevant antimicrobial peptide AP114 (plectasin derivative) was incorporated in the formulations. Peptide encapsulation and release as well as in vitro antibacterial effect were investigated. Results showed that all freeze-dried powders did form particles with liquid crystalline structure upon hydration. However, a phase transition from the bicontinuous cubic Pn3m to the reversed hexagonal was observed, as a consequence of sugar addition and the freeze-drying procedure. Data indicates that trehalose is the preferred choice of lyo-protectant in order to maintain a mono-modal particle size distribution. In addition, antimicrobial activity of AP114-containing formulations was found to be highest for the formulation containing trehalose. The release kinetics of AP114 from the nanoparticles was strongly affected by the dimensions of the hexagonal phase. Larger dimension of the hexagonal phase, significantly improved the release of AP114 and antimicrobial activity of the formulation.

Keywords
Antimicrobial peptide, AP114, Cubosome, Freeze-drying, Glycerol monooleate, Hexosome, Liquid crystal, Plectasin, Drying, Dynamic light scattering, Glycerol, High resolution transmission electron microscopy, Hydration, Liquid crystals, Low temperature drying, Microorganisms, Nanoparticles, Particle size, Particle size analysis, Peptides, Powders, Size distribution, Targeted drug delivery, Transmission electron microscopy, X ray scattering, Cubosomes, Freeze drying, Controlled drug delivery, ap 114, disaccharide, lactose, nanoparticle, polypeptide antibiotic agent, sucrose, trehalose, unclassified drug, Article, bactericidal activity, drug delivery system, drug formulation, drug release, in vitro study, kinetics, molecular stability, nonhuman, phase transition, photon correlation spectroscopy, powder, priority journal, X ray crystallography
National Category
Natural Sciences
Identifiers
urn:nbn:se:ri:diva-34070 (URN)10.1016/j.jcis.2018.03.062 (DOI)2-s2.0-85044472786 (Scopus ID)
Available from: 2018-07-06 Created: 2018-07-06 Last updated: 2024-05-22Bibliographically approved
Boge, L. (2018). Lipid-based liquid crystals as drug delivery vehicles for antimicrobial peptides. (Doctoral dissertation).
Open this publication in new window or tab >>Lipid-based liquid crystals as drug delivery vehicles for antimicrobial peptides
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The development of antimicrobial resistance is a great challenge within health sectors worldwide. Thus, demand for new, efficient treatments is urgent in order to treat various bacterial infections. Antimicrobial peptides (AMPs) are a group of antibiotics that have gained more and more attraction in the past decade. AMPs suffer from relatively low stability due to proteolytic and chemical degradation. As a consequence, carrier systems to protect the AMPs are highly needed to achieve efficient treatments in the clinic. In this thesis, lipid-based liquid crystalline (LC) structures have been examined as carriers for AMPs. LC structures of polar lipids have potential to be used as carriers and delivery systems in various pharmaceutical applications. This is due to their ability to solubilize and encapsulate hydrophilic, hydrophobic and amphiphilic substances. An important feature of these LC systems is that they can coexist with an excess of water, which enables fragmentation of the highly viscous gels into LC nanoparticles (LCNPs), i.e. cubosomes and hexosomes, in the presence of a suitable stabilizer. Peptides and proteins can be incorporated into the lipid self-assembled structures, thereby protecting them from chemical and proteolytic degradation. Cubosomes and hexosomes were investigated as drug delivery vehicles for the three AMPs: i) AP114, an improved plectasin derivative originating from the fungus Pseudoplectania nigrella, ii) DPK-060, derived from the endogenous human protein kininogen and iii) LL-37, a human AMP found in the cathelicidin family. Phase behavior, different preparation methodologies of the LCNPs, antimicrobial effect and proteolytic protection of the AMPs were studied. Moreover, the interaction between AMP-loaded particles with bacteria and bacterial mimicking membranes was investigated. Formulations aimed for pulmonary and topical administration were also evaluated. Results showed that cubic LC phases were most sensitive to the incorporation of AMPs. Depending on the nature of the AMP, different changes in the curvature of the systems were observed. Cubosomes loaded with AMPs exhibited good antimicrobial activity and were found to protect the proteolytic sensitive LL-37 from enzymatic degradation. Data strongly suggested that the release of AMP from the particles cannot solely be explained by the antimicrobial effect. Cubosomes loaded with LL-37 are thought to adsorb onto bacterial membranes, resulting in cell death.

Abstract [sv]

Många av oss har någon gång blivit tvungna att ta en penicillinkur mot halsfluss eller kanske i samband med någon annan infektion. Oftast har behandlingen varit till stor nytta, och infektioner som förr i tiden kunde leda till döden har varit lätta att behandla med hjälp av antibiotika. I takt med att vi exponerat bakterier för icke-dödliga doser antibiotika, avsiktligt eller ej, så har de under årens lopp utvecklat en stark motståndskraft (resistens) mot dessa läkemedelsmolekyler.  Antibiotikaresistens är idag en stor utmaning inom hälso- och sjukvården runt om i världen och i och med att problemet växer har det fått mycket uppmärksamhet, både i media och bland forskare. Sjukdomsalstrande bakterier har utvecklat resistens mot i princip samtliga kommersiella antibiotikum som finns att tillgå. Behovet av att framställa nya och effektiva läkemedel är således stort och kommer med största sannolikhet att öka i framtiden. Ett skräckscenario, som i dagsläget inte helt och hållet kan uteslutas, är att vi inom en snar framtid noggrant måste överväga nyttan av mindre, eller icke-akuta kirurgiska ingrepp, mot de komplikationer som en bakterieinfektion skulle kunna medföra. Men det finns gott hopp om nya effektiva behandlingsmetoder och det forskas intensivt på just detta runt om i världen. En sorts ny antibiotika som har fått mer och mer uppmärksamhet på senare tid är så kallade antimikrobiella peptider. Dessa molekyler finns i både människor och djur som en del av det naturliga försvaret mot inkräktande bakterier, virus och svampar sedan miljontals år. Forskare har lyckats isolera, modifiera och framställa helt syntetiska antimikrobiella peptider som skulle kunna utnyttjas för behandling av infektioner orsakade av bakterier. Antimikrobiella peptider attackerar bakteriens skyddande hölje (bakteriemembranet), på liknande sätt som diskmedel löser upp fett och smuts, vilket gör det mycket svårt för dem att utveckla hög resistens. Tyvärr har dessa molekylär även vissa bekymmersamma egenskaper. Till exempel så bryts de ofta snabbt ner av olika enzymer som finns i kroppen eller i direkt anslutning till infekterande områden. I vissa fall kan de brytas ner i enbart närvaro av vatten.Denna avhandling handlar om att försöka kapsla in och skydda olika antimikrobiella peptider i mycket små partiklar (<0.5 µm) tillverkade av lipider (”fetter”). Lipiderna som använts består av två kemiskt mycket olika segment; ett hydrofilt (”vattenlösligt”) och ett hydrofobt (”fettlösligt”). Detta medför att lipidmolekylerna spontant ordnar sig (själv-associerar) i mycket komplexa en-, två- och tredimensionella nanostrukturer när de blandas med vatten. De nanostrukturer som då bildas har visat sig mycket användbara för inkapsling och levererans av olika läkemedel, däribland antimikrobiella peptider. I detta arbeta har de peptidladdade partiklarnas bakteriedödande förmåga undersökts grundligt i olika modeller, och hur de tar död på bakterierna har också utretts. Det visade sig att beroende på vilken antimikrobiell peptid och vilken nanostruktur på partiklarna som användes, påverkades deras bakteriedödande förmåga drastiskt. Partiklar av kubisk nanostruktur var mest förddelaktiga att använda sig av. De kunde både skydda en antimikrobiell peptid som är känslig mot enzymatisk nedbrytning och samtidigt uppvisa bra bakteriedödande förmåga.

Publisher
p. 63
Series
Doktorsavhandlingar vid Chalmers tekniska högskola ; Ny serie: 4490
Keywords
Liquid crystals, liquid crystalline nanoparticles, cubosome, hexosome, phase behavior, antimicrobial peptide, AMP, glycerol monooleate, proteolysis, antimicrobial effect, antimicrobial resistance, bacterial membrane, membrane interaction, infection, topical delivery, pulmonary delivery
National Category
Natural Sciences
Identifiers
urn:nbn:se:ri:diva-37668 (URN)9789175978093 (ISBN)
Supervisors
Available from: 2019-07-02 Created: 2019-01-29 Last updated: 2019-07-02Bibliographically approved
Boge, L., Bysell, H., Ringstad, L., Wennman, D., Umerska, A., Cassisa, V., . . . Andersson, M. (2016). Lipid-based liquid crystals as carriers for antimicrobial peptides: Phase behavior and antimicrobial effect. Langmuir, 32(17), 4217-4228
Open this publication in new window or tab >>Lipid-based liquid crystals as carriers for antimicrobial peptides: Phase behavior and antimicrobial effect
Show others...
2016 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 32, no 17, p. 4217-4228Article in journal (Refereed) Published
Abstract [en]

The number of antibiotic-resistant bacteria is increasing worldwide, and the demand for novel antimicrobials is constantly growing. Antimicrobial peptides (AMPs) could be an important part of future treatment strategies of various bacterial infection diseases. However, AMPs have relatively low stability, because of proteolytic and chemical degradation. As a consequence, carrier systems protecting the AMPs are greatly needed, to achieve efficient treatments. In addition, the carrier system also must administrate the peptide in a controlled manner to match the therapeutic dose window. In this work, lyotropic liquid crystalline (LC) structures consisting of cubic glycerol monooleate/water and hexagonal glycerol monooleate/oleic acid/water have been examined as carriers for AMPs. These LC structures have the capability of solubilizing both hydrophilic and hydrophobic substances, as well as being biocompatible and biodegradable. Both bulk gels and discrete dispersed structures (i.e., cubosomes and hexosomes) have been studied. Three AMPs have been investigated with respect to phase stability of the LC structures and antimicrobial effect: AP114, DPK-060, and LL-37. Characterization of the LC structures was performed using small-angle X-ray scattering (SAXS), dynamic light scattering, ζ-potential, and cryogenic transmission electron microscopy (Cryo-TEM) and peptide loading efficacy by ultra performance liquid chromatography. The antimicrobial effect of the LCNPs was investigated in vitro using minimum inhibitory concentration (MIC) and time-kill assay. The most hydrophobic peptide (AP114) was shown to induce an increase in negative curvature of the cubic LC system. The most polar peptide (DPK-060) induced a decrease in negative curvature while LL-37 did not change the LC phase at all. The hexagonal LC phase was not affected by any of the AMPs. Moreover, cubosomes loaded with peptides AP114 and DPK-060 showed preserved antimicrobial activity, whereas particles loaded with peptide LL-37 displayed a loss in its broad-spectrum bactericidal properties. AMP-loaded hexosomes showed a reduction in antimicrobial activity.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2016
National Category
Physical Chemistry Pharmaceutical Sciences
Identifiers
urn:nbn:se:ri:diva-141 (URN)10.1021/acs.langmuir.6b00338 (DOI)2-s2.0-84968912179 (Scopus ID)
Available from: 2016-06-07 Created: 2016-06-07 Last updated: 2020-12-01Bibliographically approved
Matougui, N., Boge, L., Groo, A.-C., Umerska, A., Ringstad, L., Bysell, H. & Saulnier, P. (2016). Lipid-based nanoformulations for peptide delivery. International Journal of Pharmaceutics, 502(1-2), 80-97
Open this publication in new window or tab >>Lipid-based nanoformulations for peptide delivery
Show others...
2016 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 502, no 1-2, p. 80-97Article, review/survey (Refereed) Published
Abstract [en]

Nanoformulations have attracted a lot of attention because of their size-dependent properties. Among the array of nanoformulations, lipid nanoformulations (LNFs) have evoked increasing interest because of the advantages of their high degree of biocompatibility and versatility. The performance of lipid nanoformulations is greatly influenced by their composition and structure. Therapeutic peptides represent a growing share of the pharmaceutical market. However, the main challenge for their development into commercial products is their inherent physicochemical and biological instability. Important peptides such as insulin, calcitonin and cyclosporin A have been incorporated into LNFs. The association or encapsulation of peptides within lipid-based carriers has shown to protect the labile molecules against enzymatic degradation. This review describes strategies used for the formulation of peptides and some methods used for the assessment of association efficiency. The advantages and drawbacks of such carriers are also described.

Place, publisher, year, edition, pages
Elsevier, 2016
Keywords
Drug delivery, Lipids, Nanoformulations, Peptides
National Category
Other Chemistry Topics Physical Chemistry Pharmaceutical Sciences
Identifiers
urn:nbn:se:ri:diva-90 (URN)10.1016/j.ijpharm.2016.02.019 (DOI)2-s2.0-84959179307 (Scopus ID)
Available from: 2016-05-24 Created: 2016-04-28 Last updated: 2020-12-01Bibliographically approved
Mira, I. C., Andersson, M. P., Boge, L., Blute, I. A., Carlsson, G., Salminen, K., . . . Kinnunen, K. (2014). Foam forming revisited Part I. Foaming behaviour of fibre-surfactant systems. Nordic Pulp & Paper Research Journal, 29(4), 679-688
Open this publication in new window or tab >>Foam forming revisited Part I. Foaming behaviour of fibre-surfactant systems
Show others...
2014 (English)In: Nordic Pulp & Paper Research Journal, ISSN 0283-2631, E-ISSN 2000-0669, Vol. 29, no 4, p. 679-688Article in journal (Refereed) Published
Abstract [en]

The foaming properties of typical chemithermo-mechanical (CTMP) and kraft pulp paper making formulations in the presence of a series of surfactants were investigated using a lab-scale foaming set up. Foamability, foam stability, and bubble size distribution of the generated foam-fibre systems were measured. The foaming behaviour of the fibre/surfactant systems was found to be dependent on the surfactant concentration. Foams fulfilling the target requirements of air content (ca. 65% v/v air) and average bubble size (25 to 75 μm in radius) were obtained with all the seven surfactants tested. Three of the surfactants were found to allow for a rapid foaming in the system, namely sodium dodecyl sulphate (SDS), a commercial mixture of alkyl and ethoxylated alkyl sulphates, (MixSAES) and a commercial mixture of short chain alkyl glucosides (C8/C10Gluc). The rapid foaming is believed to be an intrinsic property of mixtures of surfactants with the right molecular structures and in the right proportion with respect to each other. On the other hand, the minimum surfactant concentrations required to reach the target foam volumes were lowest for surfactants with an anionic character. Further, the type of pulp fibre and the presence of GCC in the surfactant/pulp formulation were found to have very little effect on the foaming performance of the suspensions.

Place, publisher, year, edition, pages
SPCI, 2014
Keywords
Anionic surfactants, Aqueous foam, Foam stability, Foam-fibre mixture, Foamability, Non-ionic surfactants, Fibers, Kraft pulp, Mixtures, Sodium compounds, Sulfur compounds, Aqueous foams, Bubble size distributions, Commercial mixtures, Foaming properties, Sodium dodecyl sulphate, Surfactant concentrations, Chemimechanical Pulping, Foaming, Kraft Pulping, Paper Making, Surfactants
National Category
Engineering and Technology
Identifiers
urn:nbn:se:ri:diva-46133 (URN)10.3183/npprj-2014-29-04-p679-689 (DOI)2-s2.0-84914810929 (Scopus ID)
Available from: 2020-08-14 Created: 2020-08-14 Last updated: 2020-12-01Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-4742-1702

Search in DiVA

Show all publications