Recent Advances in the Structural Design of Photosensitive Agent Formulations Using "Soft" Colloidal Nanocarriers.

The growing demand for effective delivery of photosensitive active compounds has resulted in the development of colloid chemistry and nanotechnology. Recently, many kinds of novel formulations with outstanding pharmaceutical potential have been investigated with an expansion in the design of a wide variety of "soft" nanostructures such as simple or multiple (double) nanoemulsions and lipid formulations. The latter can then be distinguished into vesicular, including liposomes and "smart" vesicles such as transferosomes, niosomes and ethosomes, and non-vesicular nanosystems with solid lipid nanoparticles and nanostructured lipid carriers. Encapsulation of photosensitive agents such as drugs, dyes, photosensitizers or antioxidants can be specifically formulated by the self-assembly of phospholipids or other amphiphilic compounds. They are intended to match unique pharmaceutic and cosmetic requirements and to improve their delivery to the target site via the most common, i.e., transdermal, intravenous or oral administration routes. Numerous surface modifications and functionalization of the nanostructures allow increasing their effectiveness and, consequently, may contribute to the treatment of many diseases, primarily cancer. An increasing article number is evidencing significant advances in applications of the different classes of the photosensitive agents incorporated in the "soft" colloidal nanocarriers that deserved to be highlighted in the present review.

Recent progress in the engineering of multifunctional colloidal nanoparticles for enhanced photodynamic therapy and bioimaging.

This up-to-date review summarizes the design and current fabrication strategies that have been employed in the area of mono- and multifunctional colloidal nanoparticles - nanocarriers well suited for photodynamic therapy (PDT) and diagnostic purposes. Rationally engineered photosensitizer (PS)-loaded nanoparticles may be achieved via either noncovalent (i.e., self-aggregation, interfacial deposition, interfacial polymerization, or core-shell entrapment along with physical adsorption) or covalent (chemical immobilization or conjugation) processes. These PS loading approaches should provide chemical and physical stability to PS payloads. Their hydrophilic surfaces, capable of appreciable surface interactions with biological systems, can be further modified using functional groups (stealth effect) to achieve prolonged circulation in the body after administration and/or grafted by targeting agents (such as ligands, which bind to specific receptors uniquely expressed on the cell surface) or stimuli (e.g., pH, temperature, and light)-responsive moieties to improve their action and targeting efficiency. These attempts may in principle permit efficacious PDT, combination therapies, molecular diagnosis, and - in the case of nanotheranostics - simultaneous monitoring and treatment. Nanophotosensitizers (nano-PSs) should possess appropriate morphologies, sizes, unimodal distributions and surface processes to be successfully delivered to the place of action after systemic administration and should be accumulated in certain tumors by passive and/or active targeting. Additionally, physically facilitating drug delivery systems emerge as a promising approach to enhancing drug delivery, especially for the non-invasive treatment of deep-seated malignant tissues. Recent advances in nano-PSs are scrutinized, with an emphasis on design principles, via the promising use of colloid chemistry and nanotechnology.

The Effect of Millisecond Pulsed Electric Fields (msPEF) on Intracellular Drug Transport with Negatively Charged Large Nanocarriers Made of Solid Lipid Nanoparticles (SLN): In Vitro Study.

Drug delivery technology is still a dynamically developing field of medicine. The main direction in nanotechnology research (nanocarriers, nanovehicles, etc.) is efficient drug delivery to target cells with simultaneous drug reduction concentration. However, nanotechnology trends in reducing the carrier sizes to several nanometers limit the volume of the loaded substance and may pose a danger of uncontrolled access into the cells. On the other hand, nanoparticles larger than 200 nm in diameter have difficulties to undergo rapid diffusional transport through cell membranes. The main advantage of large nanoparticles is higher drug encapsulation efficiency and the ability to deliver a wider array of drugs. Our present study contributes a new approach with large Tween 80 solid lipid nanoparticles SLN (i.e., hydrodynamic GM-SLN-glycerol monostearate, GM, as the lipid and ATO5-SLNs-glyceryl palmitostearate, ATO5, as the lipid) with diameters DH of 379.4 nm and 547 nm, respectively. They are used as drug carriers alone and in combination with electroporation (EP) induced by millisecond pulsed electric fields. We evaluate if EP can support the transport of large nanocarriers into cells. The study was performed with two cell lines: human colon adenocarcinoma LoVo and hamster ovarian fibroblastoid CHO-K1 with coumarin 6 (C6) as a fluorescent marker for encapsulation. The biological safety of the potential treatment procedure was evaluated with cell viability after their exposure to nanoparticles and EP. The EP efficacy was evaluated by FACS method. The impact on intracellular structure organization of cytoskeleton was visualized by CLSM method with alpha-actin and beta-tubulin. The obtained results indicate low cytotoxicity of both carrier types, free and loaded with C6. The evaluation of cytoskeleton proteins indicated no intracellular structure damage. The intracellular uptake and accumulation show that SLNs do not support transport of C6 coumarin. Only application of electroporation improved the transport of encapsulated and free C6 into both treated cell lines.

Electroporation and lipid nanoparticles with cyanine IR-780 and flavonoids as efficient vectors to enhanced drug delivery in colon cancer.

Nanocarriers and electroporation (also named electropermeabilization) are convenient methods to increase drug transport. In the current study, we present an effective support of drug delivery into cancer cells, utilizing these methods. We compare the efficiency of each of them and their combination. Multifunctional solid lipid nanoparticles (SLNs) loaded with a cyanine-type IR-780 - acting as a diagnostic agent and a photosensitizer, and a flavonoid derivative - baicalein (BAI) or fisetin (FIS) as a therapeutic cargo - were fabricated via solvent-diffusion method. A therapy supplemented with flavonoids may provide a more precise method to apply desirable lower drug doses and is more likely to result in lower toxicity and a decrease in tumor growth. The SLNs were stabilized with Phospholipon 90G at various concentrations; cetyl palmitate (CP) was applied as a solid matrix. The obtained nanosystems were characterized by dynamic light scattering (size along with size distribution), UV-vis (cargos encapsulation efficiency) and atomic force microscopy (morphology and shape). The obtained SLNs were used as drug carriers alone and in combination with electropermeabilization induced by millisecond pulsed electric fields of high intensity. Two cell lines were selected for the study: LoVo and CHO-K1. The viability was assessed after electroporation alone, the use of electroporation and nanoparticles, and nanoparticles or drugs alone. The intracellular accumulation of cyanine IR-780 and the impact on intracellular structure organization of cytoskeleton was visualized with confocal microscopy method with alpha-actin and beta-tubulin. In this study, the efficacy of nanoparticles with mixed cargo, additionally enhanced by electroporation, is demonstrated to act as an anticancer modality to eliminate cancer cells.