| 1. |
- Toropainen, Tarja, et al.
(författare)
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Crystal structure changes of gamma-cyclodextrin after the SEDS process in supercritical carbon dioxide affect the dissolution rate of complexed budesonide
- 2007
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Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 24:6, s. 1058-1066
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. The present study describes the crystal structure changes of γ-cyclodextrin (γ-CD) during the solution enhanced dispersion by supercritical fluids (SEDS) process and its effect on dissolution behaviour of complexed budesonide. Materials and Methods. γ-CD solution (10 mg/ml in 50% ethanol) was pumped together with supercritical carbon dioxide through a coaxial nozzle with or without a model drug, budesonide (3.3 mg/ml). The processing conditions were 100 b and 40, 60 or 80°C. γ-CD powders were characterised before and after vacuum-drying (2-3 days at RT) with XRPD, SEM and NMR. Budesonide/γ-CD complexation was confirmed with DSC and XRPD. The dissolution behaviour of complexed budesonide was determined in aqueous solution (1% γ-CD, 37°C, 100 rpm). Results. During the SEDS process (100 b, 40 and 60°C), γ-CD and budesonide/γ-CD complexes crystallized in a tetragonal channel-type form. The vacuum-drying transformed crystalline γ-CD into amorphous form while the complexes underwent a tetragonal-to-hexagonal phase transition. The increase in the processing temperature decreased the crystallinity of γ-CD. At 80°C, amorphous γ-CD was obtained while the complexes crystallized in a hexagonal channel-type form. The dissolution behaviour of budesonide/γ-CD complexes was dependent on their crystal structure: the tetragonal form dissolved faster than the hexagonal form. Conclusions. The crystal structure of γ-CD and subsequently, the dissolution rate of complexed budesonide, can be modified with the processing conditions.
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| 2. |
- Toropainen, Tarja, et al.
(författare)
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Preparation of budesonide/gamma-cyclodextrin complexes in supercritical fluids with a novel SEDS method
- 2006
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 95:10, s. 2235-2245
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to investigate if solid drug/cyclodextrin complexes could be produced in a single-step process with a solution enhanced dispersion by supercritical fluids (SEDS) method. Budesonide and gamma-cyclodextrin (CD) solutions (50% or 99.5% ethanol) were pumped from the same (conventional method) or separate (modified method) containers together with supercritical carbon dioxide through a coaxial nozzle into a particle formation chamber. The pressure was maintained at 100, 150 or 200 bar with a temperature of 40, 60 or 80 degrees C. SEDS-processed powders were characterised with HPLC, DSC and XRPD for budesonide content, complexation and crystallinity. The budesonide dissolution rate was determined in 1% gamma-CD aqueous solution. Solid, white budesonide/gamma-CD complex particles were formed using the conventional and modified SEDS processes. The complexation efficiency was dependent on the processing conditions. For example, with the conventional method (100 bar, 60 C) the yield of the powder was 65 +/- 12% with 0.14 +/- 0.02 mg budesonide/mg powder, corresponding to 1:2 drug:CD molar ratio. The dissolution rate of this complexed budesonide (93 +/- 2% after 15 min) was markedly higher compared to unprocessed micronised budesonide (41 +/- 10%) and SEDS-processed budesonide without CD (61 +/- 3%). As a conclusion, SEDS is a novel method to produce solid drug/CD complexes in a single-step process.
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| 3. |
- Järvinen, Kristiina, et al.
(författare)
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Nanoteknologia biomateriaalien ja lääkkeiden kantaja-aineiden pintojen räätälöinnissä [Nanoscale tailoring of the surface properties of biomaterials and drug carriers]
- 2012
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Ingår i: Duodecim. - 0012-7183 .- 2242-3281. ; 128:20, s. 2085-2092
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Forskningsöversikt (refereegranskat)abstract
- Functionalities of biomaterials and drug delivery systems are improved by tailoring their surface properties using modern nanotechnology. Orthopedic implants and invasive electrodes are examples of implantable biomaterials. Biological interactions of orthopedic implants can be optimized by the synergetic effect of surface micro- and nanotexturing with a chemical composition of coating. Further, mechanical flexibility and electrochemical characteristics of invasive electrodes are improved by using micro- and nanotechnology. In nano-size drug delivery systems, surface properties of nanocarriers strongly affect their safety and efficacy. Mesoporous silicon nanoparticles are example of nanocarriers those properties can be tailored for drug delivery applications.
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| 4. |
- Rytkonen, Jussi, et al.
(författare)
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Porous Silicon-Cell Penetrating Peptide Hybrid Nanocarrier for Intracellular Delivery of Oligonucleotides
- 2014
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 11:2, s. 382-390
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Tidskriftsartikel (refereegranskat)abstract
- The largest obstacle to the use of oligonucleotides as therapeutic agents is the delivery of these large and negatively charged biomolecules through cell membranes into intracellular space. Mesoporous silicon (PSi) is widely recognized as a potential material for drug delivery purposes due to its several beneficial features like large surface area and pore volume, high loading capacity, biocompatibility, and biodegradability. In the present study, PSi nanoparticles stabilized by thermal oxidation or thermal carbonization and subsequently modified by grafting aminosilanes on the surface are utilized as an oligonucleotide carrier. Splice correcting oligonucleotides (SCOs), a model oligonucleotide drug, were loaded into the positively charged PSi nanoparticles with a loading degree as high as 14.3% (w/w). Rapid loading was achieved by electrostatic interactions, with the loading efficiencies reaching 100% within 5 min. The nanoparticles were shown to deliver and release SCOs, in its biologically active form, inside cells when formulated together with cell penetrating peptides (CPP). The biological effect was monitored with splice correction assay and confocal microscopy utilizing HeLa pLuc 705 cells. Furthermore, the use of PSi carrier platform in oligonucleotide delivery did not reduce the cell viability. Additionally, the SCO-CPP complexes formed in the pores of the carrier were stabilized against proteolytic digestion. The advantageous properties of protecting and releasing the cargo and the possibility to further functionalize the carrier surface make the hybrid nanoparticles a potential system for oligonucleotide delivery.
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