Publications by authors named "Jessica M Rosenholm"

87 Publications

Stimuli-Responsive, Plasmonic Nanogel for Dual Delivery of Curcumin and Photothermal Therapy for Cancer Treatment.

Front Chem 2020 20;8:602941. Epub 2021 Jan 20.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland.

Nanogels (Ng) are crosslinked polymer-based hydrogel nanoparticles considered to be next-generation drug delivery systems due to their superior properties, including high drug loading capacity, low toxicity, and stimuli responsiveness. In this study, dually thermo-pH-responsive plasmonic nanogel (AuNP@Ng) was synthesized by grafting poly (N-isopropyl acrylamide) (PNIPAM) to chitosan (CS) in the presence of a chemical crosslinker to serve as a drug carrier system. The nanogel was further incorporated with gold nanoparticles (AuNP) to provide simultaneous drug delivery and photothermal therapy (PTT). Curcumin's (Cur) low water solubility and low bioavailability are the biggest obstacles to effective use of curcumin for anticancer therapy, and these obstacles can be overcome by utilizing an efficient delivery system. Therefore, curcumin was chosen as a model drug to be loaded into the nanogel for enhancing the anticancer efficiency, and further, its therapeutic efficiency was enhanced by PTT of the formulated AuNP@Ng. Thorough characterization of Ng based on CS and PNIPAM was conducted to confirm successful synthesis. Furthermore, photothermal properties and swelling ratio of fabricated nanoparticles were evaluated. Morphology and size measurements of nanogel were determined by transmission electron microscopy (TEM), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). Nanogel was found to have a hydrodynamic size of ~167 nm and exhibited sustained release of curcumin up to 72 h with dual thermo-pH responsive drug release behavior, as examined under different temperature and pH conditions. Cytocompatibility of plasmonic nanogel was evaluated on MDA-MB-231 human breast cancer and non-tumorigenic MCF 10A cell lines, and the findings indicated the nanogel formulation to be cytocompatible. Nanoparticle uptake studies showed high internalization of nanoparticles in cancer cells when compared with non-tumorigenic cells and confocal microscopy further demonstrated that AuNP@Ng were internalized into the MDA-MB-231 cancer cells via endosomal route. cytotoxicity studies revealed dose-dependent and time-dependent drug delivery of curcumin loaded AuNP@Ng/Cur. Furthermore, the developed nanoparticles showed an improved chemotherapy efficacy when irradiated with near-infrared (NIR) laser (808 nm) . This work revealed that synthesized plasmonic nanogel loaded with curcumin (AuNP@Ng/Cur) can act as stimuli-responsive nanocarriers, having potential for dual therapy i.e., delivery of hydrophobic drug and photothermal therapy.
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http://dx.doi.org/10.3389/fchem.2020.602941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873892PMC
January 2021

Mesoporous Silica Nanoparticles as Carriers for Biomolecules in Cancer Therapy.

Adv Exp Med Biol 2021 ;1295:99-120

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland.

Mesoporous silica nanoparticles (MSNs) offer many advantageous properties for applications in the field of nanobiotechnology. Loading of small molecules into MSNs is straightforward and widely applied, but with the upswing of both research and commercial interest in biological drugs in recent years, also biomacromolecules have been loaded into MSNs for delivery purposes. MSNs possess many critical properties making them a promising and versatile carrier for biomacromolecular delivery. In this chapter, we review the effects of the various structural parameters of MSNs on the effective loading of biomacromolecular therapeutics, with focus on maintaining stability and drug delivery performance. We also emphasize recent studies involving the use of MSNs in the delivery of biomacromolecular drugs, especially for cancer treatment.
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http://dx.doi.org/10.1007/978-3-030-58174-9_5DOI Listing
February 2021

Fabrication and Characterization of Diclofenac Sodium Loaded Hydrogels of Sodium Alginate as Sustained Release Carrier.

Gels 2021 Jan 27;7(1). Epub 2021 Jan 27.

Department of Medical Research, School of Pharmacy, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.

The aim of the current study was to fabricate naturally derived polymer based hydrogels for controlled release of diclofenac sodium (DS) for a long duration of time. In this research work, sodium alginate-co-poly(2-acrylamido-2-methyl propane sulphonic acid) (SA-co-poly(AMPS)) hydrogels were prepared by the free radical polymerization technique, where sodium alginate (SA) and 2-acrylamido-2-methyl propane sulphonic acid (AMPS) were used as the polymer and monomer while ammonium peroxodisulfate (APS) and N,N'-Methylene bisacrylamide (MBA) were used as the initiator and cross-linker, respectively. A swelling study was performed to determine the swelling index of developed hydrogels in both acidic (pH 1.2) and basic (pH 7.4) media and pH-independent swelling was observed due to the presence of AMPS. An in vitro release study was conducted to evaluate the percentage of drug released, and a high release of the drug was found at the higher pH of 7.4. Sol-gel analysis was performed to analyze the crosslinked and uncrosslinked part of the hydrogels, and results showed a rise in gel fraction as the composition of SA, AMPS and MBA increased while the sol fraction decreased and vice versa. This work demonstrated a potential for sustained delivery of diclofenac sodium by employing various concentration of SA, AMPS and MBA.
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http://dx.doi.org/10.3390/gels7010010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930945PMC
January 2021

Cell Volume (3D) Correlative Microscopy Facilitated by Intracellular Fluorescent Nanodiamonds as Multi-Modal Probes.

Nanomaterials (Basel) 2020 Dec 23;11(1). Epub 2020 Dec 23.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 20520 Turku, Finland.

Three-dimensional correlative light and electron microscopy (3D CLEM) is attaining popularity as a potential technique to explore the functional aspects of a cell together with high-resolution ultrastructural details across the cell volume. To perform such a 3D CLEM experiment, there is an imperative requirement for multi-modal probes that are both fluorescent and electron-dense. These multi-modal probes will serve as landmarks in matching up the large full cell volume datasets acquired by different imaging modalities. Fluorescent nanodiamonds (FNDs) are a unique nanosized, fluorescent, and electron-dense material from the nanocarbon family. We hereby propose a novel and straightforward method for executing 3D CLEM using FNDs as multi-modal landmarks. We demonstrate that FND is biocompatible and is easily identified both in living cell fluorescence imaging and in serial block-face scanning electron microscopy (SB-EM). We illustrate the method by registering multi-modal datasets.
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http://dx.doi.org/10.3390/nano11010014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822478PMC
December 2020

Intranasal Nanoemulsions for Direct Nose-to-Brain Delivery of Actives for CNS Disorders.

Pharmaceutics 2020 Dec 18;12(12). Epub 2020 Dec 18.

Faculty of Pharmacy, Uttar Pradesh University of Medical Sciences, Saifai, Etawah 206130, India.

The treatment of various central nervous system (CNS) diseases has been challenging, despite the rapid development of several novel treatment approaches. The blood-brain barrier (BBB) is one of the major issues in the treatment of CNS diseases, having major role in the protection of the brain but simultaneously constituting the main limiting hurdle for drugs targeting the brain. Nasal drug delivery has gained significant interest for brain targeting over the past decades, wherein the drug is directly delivered to the brain by the trigeminal and olfactory pathway. Various novel and promising formulation approaches have been explored for drug targeting to the brain by nasal administration. Nanoemulsions have the potential to avoid problems, including low solubility, poor bioavailability, slow onset of action, and enzymatic degradation. The present review highlights research scenarios of nanoemulsions for nose-to-brain delivery for the management of CNS ailments classified on the basis of brain disorders and further identifies the areas that remain unexplored. The significance of the total dose delivered to the target region, biodistribution studies, and long-term toxicity studies have been identified as the key areas of future research.
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http://dx.doi.org/10.3390/pharmaceutics12121230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767046PMC
December 2020

Fluorescent and Electron-Dense Green Color Emitting Nanodiamonds for Single-Cell Correlative Microscopy.

Molecules 2020 Dec 13;25(24). Epub 2020 Dec 13.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 20520 Turku, Finland.

Correlative light and electron microscopy (CLEM) is revolutionizing how cell samples are studied. CLEM provides a combination of the molecular and ultrastructural information about a cell. For the execution of CLEM experiments, multimodal fiducial landmarks are applied to precisely overlay light and electron microscopy images. Currently applied fiducials such as quantum dots and organic dye-labeled nanoparticles can be irreversibly quenched by electron beam exposure during electron microscopy. Generally, the sample is therefore investigated with a light microscope first and later with an electron microscope. A versatile fiducial landmark should offer to switch back from electron microscopy to light microscopy while preserving its fluorescent properties. Here, we evaluated green fluorescent and electron dense nanodiamonds for the execution of CLEM experiments and precisely correlated light microscopy and electron microscopy images. We demonstrated that green color emitting fluorescent nanodiamonds withstand electron beam exposure, harsh chemical treatments, heavy metal straining, and, importantly, their fluorescent properties remained intact for light microscopy.
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http://dx.doi.org/10.3390/molecules25245897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764487PMC
December 2020

Self-Synthesizing Nanorods from Dynamic Combinatorial Libraries against Drug Resistant Cancer.

Angew Chem Int Ed Engl 2021 02 16;60(6):3062-3070. Epub 2020 Dec 16.

MediCity Research Laboratory, University of Turku, Tykistökatu 6, 20520, Turku, Finland.

Molecular self-assembly has been widely used to develop nanocarriers for drug delivery. However, most of them have unsatisfactory drug loading capacity (DLC) and the dilemma between stimuli-responsiveness and stability, stagnating their translational process. Herein, we overcame these drawbacks using dynamic combinatorial chemistry. A carrier molecule was spontaneously and quantitatively synthesized, aided by co-self-assembly with a template molecule and an anti-cancer drug doxorubicin (DOX) from a dynamic combinatorial library that was operated by disulfide exchange under thermodynamic control. The highly selective synthesis guaranteed a stable yet pH- and redox- responsive nanocarrier with a maximized DLC of 40.1 % and an enhanced drug potency to fight DOX resistance in vitro and in vivo. Our findings suggested that harnessing the interplay between synthesis and self-assembly in complex chemical systems could yield functional nanomaterials for advanced applications.
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http://dx.doi.org/10.1002/anie.202010937DOI Listing
February 2021

Direct Functional Protein Delivery with a Peptide into Neonatal and Adult Mammalian Inner Ear .

Mol Ther Methods Clin Dev 2020 Sep 30;18:511-519. Epub 2020 Jun 30.

ENT Institute and Otorhinolaryngology Department, Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200031, China.

The aim of this study was to study an antimicrobial peptide (AMP), aurein 1.2, which substantially increased protein delivery directly into multiple mammalian inner-ear cell types . Different concentrations of aurein 1.2 with superpositively charged GFP (+36 GFP) protein fused with Cre recombinase were delivered to postnatal day 1-2 (P1-2) and adult cochleae of Cre reporter transgenic mice with various delivery methods. By cochleostomy at different concentrations of aurein 1.2-+36 GFP (1 μM, 5 μM, 22.5 μM, and 50 μM, respectively), the tdTomato (tdT) expression was observed in outer hair cells (OHCs; 20.77%, 23.02%, 76.36%, and 92.47%, respectively) and inner hair cells (IHCs; 14.90%, 44.50%, 89.59%, and 96.13%, respectively) in the cochlea. The optimal concentration was 22.5 μM with the highest transfection efficiency and the lowest cytotoxicity. Wide-spread tdT signals were detected in the cochlear-supporting cells, utricular-supporting cells, auditory nerve, and spiral ligament in neonatal and adult mice. Compared to cochleostomy, injection through the round window membrane (RWM) also produced highly efficient tdT+ labeled cells with less cell loss. In summary, the peptide aurein 1.2 fused with +36 GFP dramatically expanded the target cells with increased efficiency in direct protein delivery in the inner ear. Aurein 1.2-+36 GFP has the potential to be developed as protein-based therapy in regeneration and genome editing in the mammalian inner ear.
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http://dx.doi.org/10.1016/j.omtm.2020.06.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477795PMC
September 2020

Assessment of Intracellular Delivery Potential of Novel Sustainable Poly(δ-decalactone)-Based Micelles.

Pharmaceutics 2020 Aug 2;12(8). Epub 2020 Aug 2.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 20520 Turku, Finland.

Biodegradable polymers from renewable resources have attracted much attention in recent years within the biomedical field. Lately, poly(δ-decalactone) based copolymer micelles have emerged as a potential drug delivery carrier material as a sustainable alternative to fossil-based polymers. However, their intracellular drug delivery potential is not yet investigated and therefore, in this work, we report on the synthesis and cellular uptake efficiency of poly(δ-decalactone) based micelles with or without a targeting ligand. Folic acid was chosen as a model targeting ligand and Rhodamine B as a fluorescent tracer to demonstrate the straightforward functionalisation aspect of copolymers. The synthesis of block copolymers was accomplished by a combination of facile ring-opening polymerisation and click chemistry to retain the structure uniformity. The presence of folic acid on the surface of micelles with diameter ~150 nm upsurge the uptake efficiency by 1.6 fold on folate receptor overexpressing MDA-MB-231 cells indicating the attainment of targeting using ligand functionality. The drug delivery capability of these carriers was ascertained by using docetaxel as a model drug, whereby the in vitro cytotoxicity of the drug was significantly increased after incorporation in micelles 48 h post incubation. We have also investigated the possible endocytosis route of non-targeted micelles and found that caveolae-mediated endocytosis was the preferred route of uptake. This work strengthens the prospect of using novel bio-based poly(δ-decalactone) micelles as efficient multifunctional drug delivery nanocarriers towards medical applications.
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http://dx.doi.org/10.3390/pharmaceutics12080726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465297PMC
August 2020

Evolution of Nanotechnology in Delivering Drugs to Eyes, Skin and Wounds via Topical Route.

Pharmaceuticals (Basel) 2020 Jul 27;13(8). Epub 2020 Jul 27.

Pharmaceutical Nanotechnology Research Laboratory, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Hyderabad 500037, Telangana, India.

The topical route is the most preferred one for administering drugs to eyes, skin and wounds for reaching enhanced efficacy and to improve patient compliance. Topical administration of drugs via conventional dosage forms such as solutions, creams and so forth to the eyes is associated with very low bioavailability (less than 5%) and hence, we cannot rely on these for delivering drugs to eyes more efficiently. An intravitreal injection is another popular drug delivery regime but is associated with complications like intravitreal hemorrhage, retinal detachment, endophthalmitis, and cataracts. The skin has a complex structure that serves as numerous physiological barriers to the entry of exogenous substances. Drug localization is an important aspect of some dermal diseases and requires directed delivery of the active substance to the diseased cells, which is challenging with current approaches. Existing therapies used for wound healing are costly, and they involve long-lasting treatments with 70% chance of recurrence of ulcers. Nanotechnology is a novel and highly potential technology for designing formulations that would improve the efficiency of delivering drugs via the topical route. This review involves a discussion about how nanotechnology-driven drug delivery systems have evolved, and their potential in overcoming the natural barriers for delivering drugs to eyes, skin and wounds.
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http://dx.doi.org/10.3390/ph13080167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463474PMC
July 2020

Recent Advances and Impact of Chemotherapeutic and Antiangiogenic Nanoformulations for Combination Cancer Therapy.

Pharmaceutics 2020 Jun 25;12(6). Epub 2020 Jun 25.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 20520 Turku, Finland.

Traditional chemotherapy, along with antiangiogenesis drugs (combination cancer therapy), has shown reduced tumor recurrence and improved antitumor effects, as tumor growth and metastasis are often dependent on tumor vascularization. However, the effect of combination chemotherapy, including synergism and additive and even antagonism effects, depends on drug combinations in an optimized ratio. Hence, nanoformulations are ideal, demonstrating a great potential for the combination therapy of chemo-antiangiogenesis for cancer. The rationale for designing various nanocarriers for combination therapy is derived from organic (polymer, lipid), inorganic, or hybrid materials. In particular, hybrid nanocarriers that consist of more than one material construct provide flexibility for different modes of entrapment within the same carrier-e.g., physical adsorption, encapsulation, and chemical conjugation strategies. These multifunctional nanocarriers can thus be used to co-deliver chemo- and antiangiogenesis drugs with tunable drug release at target sites. Hence, this review attempts to survey the most recent advances in nanoformulations and their impact on cancer treatment in a combined regimen-i.e., conventional cytotoxic and antiangiogenesis agents. The mechanisms and site-specific co-delivery strategies are also discussed herein, along with future prospects.
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http://dx.doi.org/10.3390/pharmaceutics12060592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356724PMC
June 2020

Plant-Derived Natural Biomolecule Picein Attenuates Menadione Induced Oxidative Stress on Neuroblastoma Cell Mitochondria.

Antioxidants (Basel) 2020 Jun 25;9(6). Epub 2020 Jun 25.

Department of Applied Physics, Aalto University, 00076 Espoo, Finland.

Several bioactive compounds are in use for the treatment of neurodegenerative disorders, such as Alzheimer's and Parkinson's disease. Historically, willow ( sp.) bark has been an important source of salisylic acid and other natural compounds with anti-inflammatory, antipyretic and analgesic properties. Among these, picein isolated from hot water extract of willow bark, has been found to act as a natural secondary metabolite antioxidant. The aim of this study was to investigate the unrevealed pharmacological action of picein. In silico studies were utilized to direct the investigation towards the neuroprotection abilities of picein. Our in vitro studies demonstrate the neuroprotective properties of picein by blocking the oxidative stress effects, induced by free radical generator 2-methyl-1,4-naphthoquinone (menadione, MQ), in neuroblastoma SH-SY5Y cells. Several oxidative stress-related parameters were evaluated to measure the protection for mitochondrial integrity, such as mitochondrial superoxide production, mitochondrial activity (MTT), reactive oxygen species (ROS) and live-cell imaging. A significant increase in the ROS level and mitochondrial superoxide production were measured after MQ treatment, however, a subsequent treatment with picein was able to mitigate this effect by decreasing their levels. Additionally, the mitochondrial activity was significantly decreased by MQ exposure, but a follow-up treatment with picein recovered the normal metabolic activity. In conclusion, the presented results demonstrate that picein can significantly reduce the level of MQ-induced oxidative stress on mitochondria, and thereby plays a role as a potent neuroprotectant.
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http://dx.doi.org/10.3390/antiox9060552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346164PMC
June 2020

Coculture of P. aeruginosa and S. aureus on cell derived matrix - An in vitro model of biofilms in infected wounds.

J Microbiol Methods 2020 08 25;175:105994. Epub 2020 Jun 25.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku 20520, Finland. Electronic address:

Polymicrobial biofilms are major complications of various chronic infections. Therefore, in vitro biorelevant polymicrobial biofilm models are essential tools for medical studies. This study presents an in vitro model for dual species biofilm of Pseudomonas aeruginosa and Staphylococcus aureus developed on cell-derived matrices (CDMs), in order to simulate the microenvironment of in vivo biofilms. P. aeruginosa and S. aureus are two of the most frequent pathogens in polymicrobial biofilms of wound infections. Although they are commonly isolated from polymicrobial biofilms, their interaction is antagonistic; and there is severe battle between them for nutrients and space. We introduced a nutritious formulation supporting co-cultures of P. aeruginosa and S. aureus in order to study the interaction of these gram-positive and gram-negative bacterial species. Quantitative analyses demonstrated that the enrichment of tryptic soy broth (TSB) with NaCl and glucose facilitate dual-species biofilm formation of P. aeruginosa and S. aureus when it is mixed with fetal bovine serum (FBS). Furthermore, the dual species biofilm was incubated on CDMs. Characterization of the model by fluorescent and electron microscopy techniques revealed realistic features of chronic multi-species biofilms, including competitive distribution pattern of two bacterial species and small-colony variants (SCVs) morphology of S. aureus.
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http://dx.doi.org/10.1016/j.mimet.2020.105994DOI Listing
August 2020

Anti-bacterial activity of inorganic nanomaterials and their antimicrobial peptide conjugates against resistant and non-resistant pathogens.

Int J Pharm 2020 Aug 12;586:119531. Epub 2020 Jun 12.

Pharmaceutical Sciences Laboratory, Faculty of Science & Engineering, Åbo Akademi University, 20500 Turku, Finland. Electronic address:

This review details the antimicrobial applications of inorganic nanomaterials of mostly metallic form, and the augmentation of activity by surface conjugation of peptide ligands. The review is subdivided into three main sections, of which the first describes the antimicrobial activity of inorganic nanomaterials against gram-positive, gram-negative and multidrug-resistant bacterial strains. The second section highlights the range of antimicrobial peptides and the drug resistance strategies employed by bacterial species to counter lethality. The final part discusses the role of antimicrobial peptide-decorated inorganic nanomaterials in the fight against bacterial strains that show resistance. General strategies for the preparation of antimicrobial peptides and their conjugation to nanomaterials are discussed, emphasizing the use of elemental and metallic oxide nanomaterials. Importantly, the permeation of antimicrobial peptides through the bacterial membrane is shown to aid the delivery of nanomaterials into bacterial cells. By judicious use of targeting ligands, the nanomaterial becomes able to differentiate between bacterial and mammalian cells and, thus, reduce side effects. Moreover, peptide conjugation to the surface of a nanomaterial will alter surface chemistry in ways that lead to reduction in toxicity and improvements in biocompatibility.
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http://dx.doi.org/10.1016/j.ijpharm.2020.119531DOI Listing
August 2020

Synthetic polymers from renewable feedstocks: an alternative to fossil-based materials in biomedical applications.

Ther Deliv 2020 May 15;11(5):297-300. Epub 2020 Apr 15.

Pharmaceutical Sciences Laboratory, Faculty of Science & Engineering, Åbo Akademi University, Turku, Finland.

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http://dx.doi.org/10.4155/tde-2020-0033DOI Listing
May 2020

Facile methodology of nanoemulsion preparation using oily polymer for the delivery of poorly soluble drugs.

Drug Deliv Transl Res 2020 10;10(5):1228-1240

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 20520, Turku, Finland.

Aqueous solubility of an active pharmaceutical ingredient (API) is a determining factor that has a direct impact on formulation strategies and overall bioavailability. Fabrication of nanoemulsions of poorly soluble drugs is one of the widely utilized approaches to overcome this problem. However, thermodynamic instability and tedious manufacturing processes of nanoemulsions limit their clinical translation. Therefore, this study was focused on circumventing the abovementioned hurdles by utilizing the polymer as an oil phase, instead of conventional oils. The nanoemulsion was prepared via a facile low-energy nanoprecipitation method using renewable poly(δ-decalactone) (PDL), as an oil phase and Pluronic F-68 as surfactant. The prepared nanoemulsions were characterized in terms of size, drug encapsulation efficiency, stability, and toxicity. Five different hydrophobic drugs were utilized to evaluate the drug delivery capability of the PDL nanoemulsion. The prepared nanoemulsions with sizes less than 200 nm were capable to enhance the aqueous solubility of the drugs by 3 to 10 times compared with the well-established Pluronic F-68 micelles. No phase separation or significant changes in size and drug content was observed with PDL nanoemulsions after high-speed centrifugation and 3 months of storage at two different temperatures (20 °C and 50 °C). PDL nanoemulsions were found to be non-heamolytic up to concentrations of 1 mg/mL, and the cell cytotoxicity studies on MDA-MB-231 and MEF cells suggest a concentration and time-dependent toxicity, where the PDL polymer itself induced no cytotoxicity. The results from this study clearly indicate that the PDL polymer has a tremendous potential to be utilized as an oil phase to prepare stable nanoemulsions via a facile methodology, ultimately favouring clinical translations. Graphical abstract TOC graphic.
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http://dx.doi.org/10.1007/s13346-019-00703-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447668PMC
October 2020

Nanogels as drug-delivery systems: a comprehensive overview.

Ther Deliv 2019 11 2;10(11):697-717. Epub 2019 Dec 2.

Department of Pharmacy, Faculty of Pharmacy & Alternative Medicine, The Islamia University of Bahawalpur, 63100, Punjab, Pakistan.

Nanogels have attracted considerable attention as nanoscopic drug carriers, particularly for site-specific or time-controlled delivery of bioactive mediators. A high diversity of polymer systems and the simple modification of their physicochemical features have provided multipurpose forms of nanogel preparations. Nanogels have outstandingly high stability, drug loading ability, biologic consistence, good permeation capability and can be responsive to environmental stimuli. Great potential has been shown by nanogels in many fields including delivery of genes, chemotherapy drugs, diagnosis, targeting of specific organs and several others. This review focuses mainly on different types of nanogels, methods of preparation including methods of drug loading, different modes of biodegradation mechanisms as well as main mechanisms of drug release from nanogels. Recent applications of nanogels are also briefly discussed and exemplified.
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http://dx.doi.org/10.4155/tde-2019-0010DOI Listing
November 2019

Formulation and optimization of drug-loaded mesoporous silica nanoparticle-based tablets to improve the dissolution rate of the poorly water-soluble drug silymarin.

Eur J Pharm Sci 2020 Jan 21;142:105103. Epub 2019 Oct 21.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Tykistökatu 6A, 20520 Turku, Finland. Electronic address:

Porous carriers have been put forward as a promising alternative for stabilizing the amorphous state of loaded drugs, and thus significantly improving the dissolution rate of poorly soluble compounds. The purpose of this study was to enhance the saturation solubility, dissolution rate and drug loading of the poorly water-soluble drug silymarin via incorporation into mesoporous silica nanospheres within a lyophilized tablet to obtain a unique formulation. 3 full factorial design was applied to study the effect of both independent variables, polyvinyl alcohol (PVA) as stabilizer and binder and sucrose as cryoprotectant and disintegrant; and on the dependent variables that included the mean particle size (Y), disintegration time (Y), tablet strength (Y) and % of drug release after 2 min, R,Y. The drug-loaded mesoporous silica nanospheres and the optimized formula was evaluated by different characterization methods: scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry, X-ray diffractometry and Fourier transform infrared spectroscopy; as well as drug content, saturation solubility and moisture content. The evaluation demonstrated that the loaded mesoporous silica nanospheres and the optimized formula are in amorphous state without any chemical interaction with the silica matrix or the stabilizer. Moreover, the drug was stably maintained in nanosize range with narrow particle size distribution. Furthermore, the optimized lyophilized tablets had highly porous structure, low friability (less than 1%), fast disintegration (less than 30 s), high tablet strength, low moisture content (less than 1%), remarkably increased dissolution rate and noticeable improvement in saturation solubility.
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http://dx.doi.org/10.1016/j.ejps.2019.105103DOI Listing
January 2020

Hybrid mesoporous nanorods with deeply grooved lateral faces toward cytosolic drug delivery.

Biomater Sci 2019 Dec 16;7(12):5301-5311. Epub 2019 Oct 16.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Tykistökatu 6A, Turku 20520, Finland.

Nanocarriers with high local curvatures hold a great potential of inducing effective penetration of intracellular barriers and cytosolic delivery of membrane-impermeable drugs. However, the fine control of the sharp edges and their morphological effects inside cells remains largely unexplored. Herein, a nanocarrier system of hybrid mesoporous nanorods with six-arm star-shaped end faces and groove-patterned lateral faces was developed to maximize surface regions with high local curvatures for enhancing membrane destabilization. Specifically, twisted (right-handed) nanorods (TNR, diameter ∼120, aspect ratio 4-5) with a hexagon cross-section from a templated synthesis were modified by amino groups to promote surface coating of a wet-adhesive polymer, i.e. polydopamine (PDA). An edge-preferential deposition of PDA by local curvature effects led to the protective etching of silica, and in turn, the formation of nanorods with varying groove depths at different volumes of the aqueous coating solution. Finally, branched polyethylene imine (PEI) was grafted on the exterior surface of the nanorods for enhancing the dispersity and cellular uptake rate. As verified by elaborate in vitro investigations, the configuration of nanorods with the sharpest edges/deepest grooves can be rotated to a lying-down/upright mode in order to minimize/maximize the membrane tension during the interaction with membranes, which consequently resulted in highly efficient lysosomal escape despite the relatively lower uptake degree. The successful delivery of vorinostat (SAHA, a FDA-approved histone deacetylase inhibitor) and inhibition of cancer cells demonstrated the attractive ability of the nanocarriers in drug delivery.
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http://dx.doi.org/10.1039/c9bm01251fDOI Listing
December 2019

Comparison of Polydopamine-Coated Mesoporous Silica Nanorods and Spheres for the Delivery of Hydrophilic and Hydrophobic Anticancer Drugs.

Int J Mol Sci 2019 Jul 11;20(14). Epub 2019 Jul 11.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, BioCity (3rd floor), Tykistökatu 6A, FI 20520 Turku, Finland.

Mesoporous silica nanoparticles (MSNs) have been widely studied as drug delivery systems in nanomedicine. Surface coating of MSNs have enabled them to perform efficiently in terms of bioavailability, biocompatibility, therapeutic efficacy and targeting capability. Recent studies have suggested the use of polydopamine (PDA) as a facilitative coating for MSNs that provides sustained and pH-responsive drug release, owing to the adhesive "molecular-glue" function of PDA. This further endows these hybrid MSN@PDA particles with the ability to carry large amounts of hydrophilic drugs. In this study, we expand the feasibility of this platform in terms of exploring its ability to also deliver hydrophobic drugs, as well as investigate the effect of particle shape on intracellular delivery of both a hydrophilic and hydrophobic anticancer drug. MSN@PDA loaded with doxorubicin (hydrophilic) and fingolimod (hydrophobic) was studied via a systematic in vitro approach (cellular internalization, intracellular drug distribution and cytotoxicity). To promote the cellular uptake of the MSN@PDA particles, they were further coated with a polyethylene imine (PEI)-polyethylene glycol (PEG) copolymer. Drug-loaded, copolymer-coated MSN@PDA showed effective cellular uptake, intracellular release and an amplified cytotoxic effect with both doxorubicin and fingolimod. Additionally, rods exhibited delayed intracellular drug release and superior intracellular uptake compared to spheres. Hence, the study provides an example of how the choice and design of drug delivery systems can be tuned by the need for performance, and confirms the PDA coating of MSNs as a useful drug delivery platform beyond hydrophilic drugs.
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http://dx.doi.org/10.3390/ijms20143408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679059PMC
July 2019

Quantitative bioimage analytics enables measurement of targeted cellular stress response induced by celastrol-loaded nanoparticles.

Cell Stress Chaperones 2019 07 11;24(4):735-748. Epub 2019 May 11.

Cell Biology, Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland.

The cellular stress response, which provides protection against proteotoxic stresses, is characterized by the activation of heat shock factor 1 and the formation of nuclear stress bodies (nSBs). In this study, we developed a computerized method to quantify the formation and size distribution of nSBs, as stress response induction is of interest in cancer research, neurodegenerative diseases, and in other pathophysiological processes. We employed an advanced bioimaging and analytics workflow to enable quantitative detailed subcellular analysis of cell populations even down to single-cell level. This type of detailed analysis requires automated single cell analysis to allow for detection of both size and distribution of nSBs. For specific induction of nSB we used mesoporous silica nanoparticles (MSNs) loaded with celastrol, a plant-derived triterpene with the ability to activate the stress response. To enable specific targeting, we employed folic acid functionalized nanoparticles, which yields targeting to folate receptor expressing cancer cells. In this way, we could assess the ability to quantitatively detect directed and spatio-temporal nSB induction using 2D and 3D confocal imaging. Our results demonstrate successful implementation of an imaging and analytics workflow based on a freely available, general-purpose software platform, BioImageXD, also compatible with other imaging modalities due to full 3D/4D and high-throughput batch processing support. The developed quantitative imaging analytics workflow opens possibilities for detailed stress response examination in cell populations, with significant potential in the analysis of targeted drug delivery systems related to cell stress and other cytoprotective cellular processes.
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http://dx.doi.org/10.1007/s12192-019-00999-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629742PMC
July 2019

Formulation and optimization of lyophilized nanosuspension tablets to improve the physicochemical properties and provide immediate release of silymarin.

Int J Pharm 2019 May 1;563:217-227. Epub 2019 Apr 1.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Tykistökatu 6A, 20520 Turku, Finland. Electronic address:

Silymarin (SLM) is a hepatoprotective herbal drug characterized by low aqueous solubility and, consequently, low oral bioavailability. The objective of this study was to enhance the physiochemical properties of SLM, through preparation and optimization of lyophilized nanosuspension tablets (LNTs). LNTs were prepared by sonoprecipitation technique followed by a freeze-drying process using both polyvinyl alcohol (PVA) as stabilizer and binder, and mannitol as cryoprotectant and disintegrating agent. 3 full factorial design (FFD) was applied to study the effect of independent variables at different concentrations of both PVA (X) and mannitol (X) on the dependent variables that included mean particle size (Y), disintegration time (Y), friability % (Y) and time required to release 90% of the drug (Y). Several physicochemical evaluations were implemented on the optimized formula; for instance differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy, scanning electron microscopy and transmission electron microscopy. These analyses demonstrated that the drug was in an amorphous state, stable in nanosize range and displayed no chemical interaction with the polymer. Moreover, the optimized formula had highly porous structure, rapid disintegration, friability with less than 1% and noticeable improvement in saturation solubility and dissolution rate.
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http://dx.doi.org/10.1016/j.ijpharm.2019.03.064DOI Listing
May 2019

Feasibility Study of Mesoporous Silica Particles for Pulmonary Drug Delivery: Therapeutic Treatment with Dexamethasone in a Mouse Model of Airway Inflammation.

Pharmaceutics 2019 Apr 1;11(4). Epub 2019 Apr 1.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 20520 Turku, Finland.

Diseases in the respiratory tract rank among the leading causes of death in the world, and thus novel and optimized treatments are needed. The lungs offer a large surface for drug absorption, and the inhalation of aerosolized drugs are a well-established therapeutic modality for local treatment of lung conditions. Nanoparticle-based drug delivery platforms are gaining importance for use through the pulmonary route. By using porous carrier matrices, higher doses of especially poorly soluble drugs can be administered locally, reducing their side effects and improving their biodistribution. In this study, the feasibility of mesoporous silica particles (MSPs) as carriers for anti-inflammatory drugs in the treatment of airway inflammation was investigated. Two different sizes of particles on the micron and nanoscale (1 µm and 200 nm) were produced, and were loaded with dexamethasone (DEX) to a loading degree of 1:1 DEX:MSP. These particles were further surface-functionalized with a polyethylene glycol⁻polyethylene imine (PEG⁻PEI) copolymer for optimal aqueous dispersibility. The drug-loaded particles were administered as an aerosol, through inhalation to two different mice models of neutrophil-induced (by melphalan or lipopolysaccharide) airway inflammation. The mice received treatment with either DEX-loaded MSPs or, as controls, empty MSPs or DEX only; and were evaluated for treatment effects 24 h after exposure. The results show that the MEL-induced airway inflammation could be treated by the DEX-loaded MSPs to the same extent as free DEX. Interestingly, in the case of LPS-induced inflammation, even the empty MSPs significantly down-modulated the inflammatory response. This study highlights the potential of MSPs as drug carriers for the treatment of diseases in the airways.
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http://dx.doi.org/10.3390/pharmaceutics11040149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523761PMC
April 2019

Green Nanotechnology: Advancement in Phytoformulation Research.

Medicines (Basel) 2019 Mar 14;6(1). Epub 2019 Mar 14.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 20520 Turku, Finland.

The ultimate goal of any scientific development is to increase well-being and human health. Novel strategies are required for the achievement of safe and effective therapeutic treatments beyond the conventional ones, and society needs new requirements for new technologies, moving towards clean and green technology development. Green nanotechnology is a branch of green technology that utilizes the concepts of green chemistry and green engineering. It reduces the use of energy and fuel by using less material and renewable inputs wherever possible. Green nanotechnology, in phytoformulations, significantly contributes to environmental sustainability through the production of nanomaterials and nanoproducts, without causing harm to human health or the environment. The rationale behind the utilization of plants in nanoparticle formulations is that they are easily available and possess a broad variability of metabolites, such as vitamins, antioxidants, and nucleotides. For instance, gold (Au) nanoparticles have attracted substantial attention for their controllable size, shape, and surface properties. A variety of copper (Cu) and copper oxide (CuO) nanoparticles have also been synthesized from plant extracts. Titanium dioxide and zinc oxide nanoparticles are also important metal oxide nanomaterials that have been synthesized from a number of plant extracts. International and domestic laws, government and private-party programs, regulations and policies are being carefully reviewed and revised to increase their utility and nurture these nanoscale materials for commercialization. Inspiring debates and government initiatives are required to promote the sustainable use of nanoscale products. In this review, we will discuss the potential of the utilization of plant extracts in the advancement of nanotechnology.
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http://dx.doi.org/10.3390/medicines6010039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6473607PMC
March 2019

CaP coated mesoporous polydopamine nanoparticles with responsive membrane permeation ability for combined photothermal and siRNA therapy.

Acta Biomater 2019 03 3;86:416-428. Epub 2019 Jan 3.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, No. 174 Shazheng Road, Chongqing 400044, China.

Combined photothermal and gene therapy provides a promising modality toward cancer treatment, yet facile integration and controlled codelivery of gene payloads and photothermal conversion agents (PTCAs) remains a great challenge. Inspired by the robust wet adhesion of marine mussels, we present a rationally designed nanosystem constructed by using hybrid mesoporous polydopamine nanoparticles (MPDA) with sub-100 nm sizes and a high photothermal conversion efficiency of 37%. The surface of the particles were modified with tertiary amines by the facile Michael addition/Schiff base reactions of PDA to realize high siRNA loading capacity (10 wt%). Moreover, a successful calcium phosphate (CaP) coating via biomineralization was constructed on the cationic nanoparticle to prohibit premature release of siRNA. The CaP coating underwent biodegradation in weakly-acidic subcellular conditions (lysosomes). The synergistic integration of tertiary amines and catechol moieties on the subsequently exposed surfaces was demonstrated to feature the destabilization/disruption ability toward model cellular membranes via the greatly enhanced interfacial adhesion and interactions. Consequently, sufficient permeability of lysosomal membranes, and in turn, a high lysosomal escape efficiency, was realized, which then resulted in high gene silencing efficiencies via sufficient cytosolic delivery of siRNA. When an efficient knocking down (65%) of survivin (an inhibitor of apoptosis proteins) was combined with a subsequent photothermal ablation, remarkably higher therapeutic efficiencies were observed both in vitro and in vivo, as compared with monotherapy. The system may help to pave a new avenue on the utilization of bio-adhesive surfaces for handling the obstacles of combined photothermal and gene therapy. STATEMENT OF SIGNIFICANCE: Polydopamine (PDA) based porous photothermal-conversion agent (PTCA) with sufficiently high conversion efficiency was employed to deliver photothermal/gene therapy modalities towards cancer treatment. CaP coating via PDA-induced biomineralization was constructed to prohibit premature release of siRNA loaded in the pore space of the nanocarriers. Responsive degradation of CaP also led to the exposure of membrane-lytic surfaces built through the synergistic integration of tertiary amines and catechol moieties, and in turn the significantly enhanced lysosomal escape and cytosol siRNA delivery. Therapeutic targeting of survivin was successfully applied for activation of apoptosis and programmed cell death. Combined photothermal and gene therapy improved therapeutic effectiveness.
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http://dx.doi.org/10.1016/j.actbio.2019.01.002DOI Listing
March 2019

Role of Polymers in 3D Printing Technology for Drug Delivery - An Overview.

Curr Pharm Des 2018 ;24(42):4979-4990

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Abo Akademi University, 20520 Turku, Finland.

Background: 3D printing (3DP) is an emerging technique for fabrication of a variety of structures and complex geometries using 3D model data. In 1986, Charles Hull introduced stereolithography technique that took advances to beget new methods of 3D printing such as powder bed fusion, fused deposition modeling (FDM), inkjet printing, and contour crafting (CC). Being advantageous in terms of less waste, freedom of design and automation, 3DP has been evolved to minimize incurred cost for bulk production of customized products at the industrial outset. Due to these reasons, 3DP technology has acquired a significant position in pharmaceutical industries. Numerous polymers have been explored for manufacturing of 3DP based drug delivery systems for patient-customized medication with miniaturized dosage forms.

Method: Published research articles on 3D printed based drug delivery have been thoroughly studied and the polymers used in those studies are summarized in this article.

Results: We have discussed the polymers utilized to fabricate 3DP systems including their processing considerations, and challenges in fabrication of high throughput 3DP based drug delivery systems.

Conclusion: Despite several advantages of 3DP in drug delivery, there are still a few issues that need to be addressed such as lower mechanical properties and anisotropic behavior, which are obstacles to scale up the technology. Polymers as a building material certainly plays crucial role in the final property of the dosage form. It is an effort to bring an assemblage of critical aspects for scientists engaged in 3DP technology to create flexible, complex and personalized dosage forms.
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http://dx.doi.org/10.2174/1381612825666181226160040DOI Listing
November 2019

Factors Affecting Intracellular Delivery and Release of Hydrophilic Versus Hydrophobic Cargo from Mesoporous Silica Nanoparticles on 2D and 3D Cell Cultures.

Pharmaceutics 2018 Nov 17;10(4). Epub 2018 Nov 17.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 20521 Turku, Finland.

Intracellular drug delivery by mesoporous silica nanoparticles (MSNs) carrying hydrophilic and hydrophobic fluorophores as model drug cargo is demonstrated on 2D cellular and 3D tumor organoid level. Two different MSN designs, chosen on the basis of the characteristics of the loaded cargo, were used: MSNs with a surface-grown poly(ethylene imine), PEI, coating only for hydrophobic cargo and MSNs with lipid bilayers covalently coupled to the PEI layer as a diffusion barrier for hydrophilic cargo. First, the effect of hydrophobicity corresponding to loading degree (hydrophobic cargo) as well as surface charge (hydrophilic cargo) on intracellular drug release was studied on the cellular level. All incorporated agents were able to release to varying degrees from the endosomes into the cytoplasm in a loading degree (hydrophobic) or surface charge (hydrophilic) dependent manner as detected by live cell imaging. When administered to organotypic 3D tumor models, the hydrophilic versus hydrophobic cargo-carrying MSNs showed remarkable differences in labeling efficiency, which in this case also corresponds to drug delivery efficacy in 3D. The obtained results could thus indicate design aspects to be taken into account for the development of efficacious intracellular drug delivery systems, especially in the translation from standard 2D culture to more biologically relevant organotypic 3D cultures.
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http://dx.doi.org/10.3390/pharmaceutics10040237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320991PMC
November 2018

Core-Shell Structures of Upconversion Nanocrystals Coated with Silica for Near Infrared Light Enabled Optical Imaging of Cancer Cells.

Micromachines (Basel) 2018 Aug 14;9(8). Epub 2018 Aug 14.

School of Basic Sciences and Advanced Materials Research Center, Indian Institute of Technology Mandi, Kamand, Mandi 175005, Himachal Pradesh, India.

Optical imaging of cancer cells using near infrared (NIR) light is currently an active area of research, as this spectral region directly corresponds to the therapeutic window of biological tissues. Upconversion nanocrystals are photostable alternatives to conventional fluorophores. In our work, we have prepared upconversion nanocrystals of NaYF₄:Yb/Er and encapsulated them in silica to form core-shell structures. The as-prepared core-shell nanostructures have been characterized for their structure, morphology, and optical properties using X-ray diffraction, transmission electron microscopy coupled with elemental mapping, and upconversion luminescence spectroscopy, respectively. The cytotoxicity examined using cell viability assay indicated a low level of toxicity of these core-shell nanostructures. Finally, these core-shell nanostructures have been utilized as photostable probes for NIR light enabled optical imaging of human breast cancer cells. This work paves the way for the development of advanced photostable, biocompatible, low-toxic core-shell nanostructures for potential optical imaging of biological cells and tissues.
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http://dx.doi.org/10.3390/mi9080400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6187455PMC
August 2018

Characterization of modified mesoporous silica nanoparticles as vectors for siRNA delivery.

Asian J Pharm Sci 2018 Nov 21;13(6):592-599. Epub 2018 Feb 21.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, BioCity, Artillerigatan 6A, FI 20520 Turku, Finland.

Gene therapy using siRNA molecules is nowadays considered as a promising approach. For successful therapy, development of a stable and reliable vector for siRNA is crucial. Non-viral and non-organic vectors like mesoporous silica nanoparticles (MSN) are associated with lack of most viral vector drawbacks, such as toxicity, immunogenicity, but also generally a low nucleic acid carrying capacity. To overcome this hurdle, we here modified the pore walls of MSNs with surface-hyperbranching polymerized poly(ethyleneimine) (hbPEI), which provides an abundance of amino-groups for loading of a larger amount of siRNA molecules via electrostatic adsorption. After loading, the particles were covered with a second layer of pre-polymerized PEI to provide better protection of siRNA inside the pores, more effective cellular uptake and endosomal escape. To test the transfection efficiency of PEI covered siRNA/MSNs, MDA-MB 231 breast cancer cells stably expressing GFP were used. We demonstrate that PEI-coated siRNA/MSN complexes provide more effective delivery of siRNAs compared to unmodified MSNs. Thus, it can be concluded that appropriately surface-modified MSNs can be considered as prospective vectors for therapeutic siRNA delivery.
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http://dx.doi.org/10.1016/j.ajps.2018.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7032096PMC
November 2018

Solid Lipid Nanoparticles: Emerging Colloidal Nano Drug Delivery Systems.

Pharmaceutics 2018 Oct 18;10(4). Epub 2018 Oct 18.

Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Abo Akademi University, 20520 Turku, Finland.

Solid lipid nanoparticles (SLNs) are nanocarriers developed as substitute colloidal drug delivery systems parallel to liposomes, lipid emulsions, polymeric nanoparticles, and so forth. Owing to their unique size dependent properties and ability to incorporate drugs, SLNs present an opportunity to build up new therapeutic prototypes for drug delivery and targeting. SLNs hold great potential for attaining the goal of targeted and controlled drug delivery, which currently draws the interest of researchers worldwide. The present review sheds light on different aspects of SLNs including fabrication and characterization techniques, formulation variables, routes of administration, surface modifications, toxicity, and biomedical applications.
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http://dx.doi.org/10.3390/pharmaceutics10040191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321253PMC
October 2018