Browsing by Author "Airaksinen, Anu J."

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  • Delivery of agents into articular cartilage with electric spark-induced sound waves
    (2018-10-16) Pérez, Alejandro García; Nieminen, Heikki J.; Finnilä, Mikko; Salmi, Ari; Pritzker, Kenneth P.H.; Lampsijärvi, Eetu; Paulin, Tor; Airaksinen, Anu J.; Saarakkala, Simo; Hæggström, Edward
     A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
    Localized delivery of drugs into articular cartilage (AC) may facilitate the development of novel therapies to treat osteoarthritis (OA). We investigated the potential of spark-gap-generated sound to deliver a drug surrogate, i.e., methylene blue (MB), into AC. In vitro experiments exposed bovine AC samples to either simultaneous sonication and immersion in MB (Treatment 1; n = 10), immersion in MB after sonication (Control 1; n = 10), solely immersion in MB (Control 2; n = 10), or neither sonication nor immersion in MB (Control 3; n = 10). The sonication protocol consisted of 1,000 spark-gap -generated pulses. Delivery of MB into AC was estimated from optical absorbance in transmission light microscopy. Optical absorbance was significantly greater in the treatment group up to 900 μm depth from AC surface as compared to all controls. Field emission scanning electron microscopy (FESEM), histological analysis, and digital densitometry (DD) of sonicated (n = 6) and non-sonicated (n = 6) samples showed no evidence of sonication-induced changes in proteoglycan content or collagen structure. Consequently, spark-gap -generated sound may offer a solution for localized drug delivery into AC in a non-destructive fashion. Further research on this method may contribute to OA drug therapies.
  • Localized delivery of compounds into articular cartilage by using high-intensity focused ultrasound
    (2019-12-01) Nieminen, Heikki J.; Lampsijärvi, Eetu; Barreto, Gonçalo; Finnilä, Mikko A.J.; Salmi, Ari; Airaksinen, Anu J.; Eklund, Kari K.; Saarakkala, Simo; Pritzker, Kenneth P.H.; Hæggström, Edward
     A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
    Localized delivery of drugs into an osteoarthritic cartilaginous lesion does not yet exist, which limits pharmaceutical management of osteoarthritis (OA). High-intensity focused ultrasound (HIFU) provides a means to actuate matter from a distance in a non-destructive way. In this study, we aimed to deliver methylene blue locally into bovine articular cartilage in vitro. HIFU-treated samples (n = 10) were immersed in a methylene blue (MB) solution during sonication (f = 2.16 MHz, peak-positive-pressure = 3.5 MPa, mechanical index = 1.8, pulse repetition frequency = 3.0 kHz, cycles per burst: 50, duty cycle: 7%). Adjacent control 1 tissue (n = 10) was first pre-treated with HIFU followed by immersion into MB; adjacent control 2 tissue (n = 10) was immersed in MB without ultrasound exposure. The MB content was higher (p < 0.05) in HIFU-treated samples all the way to a depth of 600 µm from AC surface when compared to controls. Chondrocyte viability and RNA expression levels associated with cartilage degeneration were not different in HIFU-treated samples when compared to controls (p > 0.05). To conclude, HIFU delivers molecules into articular cartilage without major short-term concerns about safety. The method is a candidate for a future approach for managing OA.
  • Radiolabeled Molecular Imaging Probes for the In Vivo Evaluation of Cellulose Nanocrystals for Biomedical Applications
    (2019-02-11) Imlimthan, Surachet; Otaru, Sofia; Keinänen, Outi; Correia, Alexandra; Lintinen, Kalle; Santos, Helder A.; Airaksinen, Anu J.; Kostiainen, Mauri; Sarparanta, Mirkka
     A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
    Cellulose nanocrystals (CNCs) have remarkable potential to improve the delivery of diagnostic and therapeutic agents to tumors; however, the in vivo studies on CNC biodistribution are still limited. We developed CNC-based imaging probes for the in vitro and in vivo evaluation using two labeling strategies: site-specific hydrazone linkage to the terminal aldehyde of the CNC and nonsite-specific activation using 1,1′-carbonyldiimidazole (CDI). The in vivo behavior of unmodified CNC, DOTA-CNC (ald.), and DOTA-CNC (OH) was investigated in healthy and 4T1 breast cancer mouse models. They displayed good biocompatibility in cell models. Moreover, the biodistribution profile and SPECT/CT imaging confirmed that the accumulation of 111 In-labeled DOTA-CNC (ald.) and 111 In-DOTA-CNC (OH) was primarily in hepatic, splenic, and pulmonary ducts in accordance with the clearance of nontargeted nanoparticles. The developed CNC imaging probes can be used to obtain information with noninvasive imaging on the behavior in vivo to guide structural optimization for targeted delivery.
  • A Theranostic Cellulose Nanocrystal-Based Drug Delivery System with Enhanced Retention in Pulmonary Metastasis of Melanoma
    (2021-05-06) Imlimthan, Surachet; Khng, You Cheng; Keinänen, Outi; Zhang, Wenzhong; Airaksinen, Anu J.; Kostiainen, Mauri A.; Zeglis, Brian M.; Santos, Hélder A.; Sarparanta, Mirkka
     A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
    Metastatic melanoma can be difficult to detect until at the advanced state that decreases the survival rate of patients. Several FDA-approved BRAF inhibitors have been used for treatment of metastatic melanoma, but overall therapeutic efficacy has been limited. Lutetium-177 (177Lu) enables simultaneous tracking of tracer accumulation with single-photon emission computed tomography and radiotherapy. Therefore, the codelivery of 177Lu alongside chemotherapeutic agents using nanoparticles (NPs) might improve the therapeutic outcome in metastatic melanoma. Cellulose nanocrystals (CNC NPs) can particularly deliver payloads to lung capillaries in vivo. Herein, 177Lu-labeled CNC NPs loaded with vemurafenib ([177Lu]Lu-CNC-V NPs) is developed and the therapeutic effect in BRAF V600E mutation-harboring YUMM1.G1 murine model of lung metastatic melanoma is investigated. The [177Lu]Lu-CNC-V NPs demonstrate favorable radiolabel stability, drug release profile, cellular uptake, and cell growth inhibition in vitro. In vivo biodistribution reveals significant retention of the [177Lu]Lu-CNC-V NPs in the lung, liver, and spleen. Ultimately, the median survival time of animals is doubly increased after treatment with [177Lu]Lu-CNC-V NPs compared to control groups. The enhanced therapeutic efficacy of [177Lu]Lu-CNC-V NPs in the lung metastatic melanoma animal model provides convincing evidence for the potential of clinical translation for theranostic CNC NP-based drug delivery systems after intravenous administration.