Clinic-oriented injectable smart material for the treatment of diabetic wounds: Coordinating the release of GM-CSF and VEGF.

Chronic wounds are often caused by diabetes and present a challenging clinical problem due to vascular problems leading to ischemia. This inhibits proper wound healing by delaying inflammatory responses and angiogenesis. To address this problem, we have developed injectable particle-loaded hydrogels which sequentially release Granulocyte-macrophage- colony-stimulating-factor (GM-CSF) and Vascular endothelial growth factor (VEGF) encapsulated in polycaprolactone-lecithin-geleol mono-diglyceride hybrid particles. GM-CSF promotes inflammation, while VEGF facilitates angiogenesis. The hybrid particles (200-1000 nm) designed within the scope of the study can encapsulate the model proteins Bovine Serum Albumin 65 ±â€¯5 % and Lysozyme 77 ±â€¯10 % and can release stably for 21 days. In vivo tests and histological findings revealed that in the hydrogels containing GM-CSF/VEGF-loaded hybrid particles, wound depth decreased, inflammation phase increased, and fibrotic scar tissue decreased, while mature granulation tissue was formed on day 10. These findings confirm that the hybrid particles first initiate the inflammation phase by delivering GM-CSF, followed by VEGF, increasing the number of vascularization and thus increasing the healing rate of wounds. We emphasize the importance of multi-component and sequential release in wound healing and propose a unifying therapeutic strategy to sequentially deliver ligands targeting wound healing stages, which is very important in the treatment of the diabetic wounds.

Tadpole-Like Anisotropic Polymer/Lipid Janus Nanoparticles for Nose-to-Brain Drug Delivery: Importance of Geometry, Elasticity on Mucus-Penetration Ability.

Asymmetric geometry (aspect ratio >1), moderate stiffness (i.e., semielasticity), large surface area, and low mucoadhesion of nanoparticles are the main features to reach the brain by penetrating across the nasal mucosa. Herein, a new application has been presented for the use of multifunctional Janus nanoparticles (JNPs) with controllable geometry and size as a nose-to-brain (N2B) delivery system by changing proportions of Precirol ATO 5 and polycaprolactone compartments and other operating conditions. To bring to light the N2B application of JNPs, the results are presented in comparison with polymer and solid lipid nanoparticles, which are frequently used in the literature regarding their biopharmaceutical aspects: mucoadhesion and permeability through the nasal mucosa. The morphology and geometry of JPs were observed via cryogenic-temperature transmission electron microscopy images, and their particle sizes were verified by dynamic light scattering, atomic force microscopy, and scanning electron microscopy. Although all NPs showed penetration across the mucus barrier, the best increase in penetration was observed with asymmetric and semielastic JNPs, which have low interaction ability with the mucus layer. This study presents a new and promising field of application for a multifunctional system suitable for N2B delivery, potentially benefiting the treatment of brain tumors and other central nervous system diseases.

Carthamus Tinctorius L. (Safflower) extracts inhibit expression of metastatic genes of MDA-MB-231 breast cancer cells.

Breast cancer is the most common type of cancer in women and the second  cause of cancer-related death after lung cancer. Although the common methods used in the treatment of breast cancer are chemotherapy, radiotherapy and surgery, the search for alternative treatments continues.  The leading  alternative treatments are medicinal plants which actually inspire the production of many cancer drugs. In this study, the proliferative and metastatic effects of Carthamus tinctorius L., known for its many therapeutic properties, on metastatic breast cancer were investigated. Here, intending to evaluate the the content and actions of different extracts of safflower leaves extracts were prepared by extracting in water, alcohol and oil and analysed by FTIR. Their antioxidant effect was tested and then the extracts were applied to metastatic breast cancer cells. FTIR spectrums of all three extracts have revealed the presence of organic compounds.  It is found that all extracts but mostly the oil extract has antioxidant property. MTT assay, wound healing assay and gene expression analysis were performed to assess the antiproliferative and anti metastatic effects of the extracts on breast cancer cells. It is found that, there is no significant antiproliferative effect of extracts on MDA-MB-231 cells except the alcohol extract. However, all safflower extracts, especially the oil extract, significantly reduced the metastatic potential of breast cancer cells. It is concluded that safflower contents are potent chemicals which inhibit the cellular mechanisms underlying the spreading of cancer cells and further analysis may lead to new initiatives in drug design research.

Preparation of magnetic nanoparticle integrated nanostructured lipid carriers for controlled delivery of ascorbyl palmitate.

Most cancer treatments can cause vital side effects on healthy tissues. Ascorbic acid (AA) is a water-soluble antioxidant molecule and possesses a variety of functions such as prevention of tumor proliferation and treatment of cancer. However, AA, is very sensitive to air, heat and light. Its high hydrophilicity also makes the controlled delivery difficult. To overcome these problems, AA can be chemically-modified and made more hydrophobic by the esterification. Palmitic acid is one of the most common long-chain fatty acids that can be used for this purpose. It is known that Ascorbyl palmitate (AP) which is a lipopihilic derivative of AA, can inhibit cell proliferation and DNA synthesis in many types of cancer. Although AP has higher stability, its bioavailability and therapeutic effect is low due to its lipophilicity and low release capacity.•In this study, nanostructured lipid carriers (NLC) which are colloidal nanoparticles with high biocompatibility, low crystallinity and high hydrophobic-drug encapsulation capacity was prepared to increase the bioavailability of AP.•To provide triggered drug release via hyperthermia, magnetic nanoparticles (MNps) were integrated into the NLCs besides AP.•The synthesis of biocompatible NLCs with controlled and triggered release ability, is successfully completed and controlled release of AP as an antitumor agent is achieved.

Stimuli-responsive lipid nanotubes in gel formulations for the delivery of doxorubicin.

Lipid nanotubes (LNTs) are one of the most advantageous structures for drug delivery and targeting. LNTs formed by a specially designed molecule called AQUA (AQ-NH-(CH2)10COOH (AQ: anthraquinone group) is used for drug delivery, and doxorubicin (DOX) is the drug selected. DOX and AQUA have some similarities in their molecular structures, so a significant amount of DOX can be loaded to LNTs. The AQUA LNTs are pH responsive, and drug loading increased almost linearly by increasing the pH, reaching a maximum value (96%) at pH 9.0. In terms of drug release, lower pHs are preferred. Drug-loaded LNTs are also mixed with four different gels (chitosan, alginate, hydroxypropyl methylcellulose and polycarbophil) to use the advantages of these gels. The drug release efficiency is studied using a Franz diffusion cell in which sheep colon membranes and dialysis membranes are utilized. The amount of released DOX from the chitosan gel formulations was quite high. Sodium alginate gels had lower release and slower diffusion of DOX. The cytotoxic effect of DOX-loaded AQUA LNTs has also been determined on cell cultures. Our new lipid nanotubes are a non-toxic, effective, biodegradable, biocompatible, stable and promising system for drug delivery and can be used for colonic administration of DOX for the treatment of colorectal cancer (CRC).