Nanomedicine Journal
Volume:11 Issue: 2, Spring 2024

Neurological disorders are the diseases associated with the central and peripheral nervous system. They are among the most serious and prevalent diseases nowadays. However, most of the pharmacological agents used to treat neurological disorders demonstrate severe toxicities and side effects, along with failure to achieve the desired outcomes due to their inability to cross the blood-brain barrier (BBB). Therefore, efforts have been made to develop potential drug carriers that can enhance the penetration of various therapeutic agents across the BBB. Due to the remarkable selectivity of nanoparticles and their ability to penetrate the BBB, they have attracted enormous interest as a viable solution to overcome these challenges. Polymeric nanoparticles used as drug delivery systems, in particular, demonstrated multiple advantages over traditional drug delivery systems in the treatment of neurological and psychological disorders due to several beneficial properties. This minireview article discusses the current literature on the use of chitosan nanoparticles in particular as promising carriers for delivering therapeutic agents to the brain for the treatment of different neurological diseases. The article emphasizes the advantages of using chitosan over other natural and synthetic polymers, and illustrates the methods of preparation of chitosan nanoparticles, in addition to the characterization of chitosan-based nanoparticles. The article also discusses the specific application of chitosan-based nanoparticles for brain targeting with the aim of the treatment of neurological disorders. Furthermore, challenges and future prospects were also discussed.

Cubosomes are the aqueous dispersions of lipid-based liquid-crystalline bi-continuous phases, with the inner structure comprised of triply periodic, non-intersecting, curved, bilayers folded in cubic symmetry, and are organized to form two disjoined continuous water channels on an infinite periodic minimal surface. This review emphasized the peer findings about history and origin of cubosomes, including preparation, characterization and evaluation techniques, along with its promising features as a bio-therapeutics biodegradable cargo nano-material in descriptive manner. The structures of cubosomes, e.g. Q223, Q227, Q212, Q230 etc. are discussed here reflecting their versatile applicability. The automated cubosome preparation method in addition to the general preparation methods and assessment of cubosomes with the aid of both, ordinary visual characterization as well as sophisticated instruments like cryo-TEM, Cryo-FESEM, SAXS, LUMiFuge® have been described. Physical parameter’s quantification approves the drug-carriers system fit in therapeutics, i.e stability analysis, permeation, entrapment efficiency (EE), loading capacity (LC), drug content of dispersions, in-vitro drug release studies, HPLC analysis, in-vivo studies, etc., which are framed here in detail. Cubosomes owes the versatility and desired characteristic of a nanoparticle for drug delivery and other biomedical applications. Therefore, we have described here the up to date wide area applications of cubosomes administered through various routes.

Selenium Nanoparticles can modulate the function of the immune system and improve immunity. We investigate the expression of toll-like receptor-7 (TLR-7), myeloid differentiation primary response 88 (MyD88), Nuclear factor kappa B (NF-κB), and TNF receptor associated factor 6 (TRAF6) genes in thymus of Wistar rats following treatment with cyclosporine A (CsA) and Nano-selenium (Nano-Se) supplementation.  Twenty-four male Wistar rats (200-220 grams) were divided into 3 groups of control (n=8), CsA (n=8), and CsA+Nano-Se (n=8). Rats in CsA and CsA+Nano-Se group’s received cyclosporine A and olive oil solution by subcutaneous injection for 10 days at a dose of 5 mg/kg/day. Nano-Se with a dose of 2.5 mg/kg of body weight was gavaged to the CsA+Nano-Se group once a day and 3 times a week. Real-time PCR were used for gene expression of TLR-7, MyD88, NF-kB, and TRAF6 at thymus.  The result of this study show that CsA significantly decreased expressions of TLR-7, MyD88, NF-kB, and TRAF6 at thymus compared to control group (P<0.05). However, expressions of TLR-7, MyD88, NF-kB, and TRAF6 at thymus in  CsA+ Nano-Se group was significantly increased compared to CsA group (P<0.05).  Nano-Se supplementation significantly regulated the expression of TLR-7, MyD88, NF-kB and TRAF6 genes in the thymus of rats treated with cyclosporine A. Therefore, Nano-Se supplementation can be recommended to boost immune function after using immunosuppressive drugs. However, more research is needed in the future.

Calcium phosphates, particularly hydroxyapatite, are the main inorganic compounds of vertebrate bone.In this study, nanohydroxyapatite was prepared using kombucha Symbiotic Culture of Bacteria and Yeast (SCOBY), and its effect was investigated on osteoporosis in ovariectomized rats.  Kombucha-nanohydroxyapatite was synthesized by adding phosphoric acid to the kambucha scoby. Characterization of the nanoparticle was performed through X-ray diffraction, X-ray fluorescence, and transmission electron microscopy techniques. Female rats were divided into 5 groups: control, ovariectomized groups, and three ovariectomized groups treated with concentrations of 25, 50, and 100 mg/kg of nanoparticles. At the end of the treatment period, the levels of calcium, phosphorus, parathyroid hormone, and activity of alkaline phosphatase were measured in the blood samples. Calcium and phosphorus levels were also measured in bone and liver. The bone was evaluated histopathologically. The synthesis of nanohydroxyapatite with particle size of 30 nm was confirmed through the use of X-ray diffraction (XRD) and TEM techniques. A significant increase in calcium and phosphorus levels in the femur bone was observed in the ovariectomized group, which received the highest nanoparticle concentration compared to the ovariectomized group. Parathyroid hormone and alkaline phosphatase activity inhibition were increased in ovariectomized rats following treatment with the highest nanoparticle concentration. In the mentioned group, bone trabeculae proliferation and increased lacuna-containing osteocytes were also observed. This study suggested that the highest concentration of kombucha-nanohydroxyapatite could be partially absorbed into bone tissues and recover the bone-destructive changes caused by ovariectomy, although additional experiments are needed for confirmation.

Colorectal cancer is the second deadly cancer for men and women worldwide. Depending on the pathological attributes of the tumor, there are numerous therapeutic options for colorectal cancer treatment. Chemotherapy is one of the main methods, however, due to the low solubility and short half-life of chemotherapy drugs, this treatment method has limitations. 5-Fu and curcumin are important drugs for the treatment of colorectal cancer. One of the primary resolutions is the application of bioanalytical techniques, which involve the utilization of chemotherapy agents in conjunction with nanoparticles, thereby facilitating the directed transportation of the therapeutic substance to malignant cells.  In this study, Polycaprolactone- Polyethylene glycol- Hyaluronic acid (PCL-PEG-HA) copolymers and magnetic nanoparticle iron-cobalt (FeCo) were synthesized to deliver Curcumin (CU), 5-Fluorouracil (5-Fu) and the combination to HCT116 colorectal cancer cells. To control the release of CU and 5-FU and in vivo tumor targeting, PCL-PEG-HA/FeCo were synthesized and then characterized for the morphological characteristics, shape, and magnetic properties of the nanoparticles, drug retention efficiency, and release pattern in two acidic and neutral environments.  Our results demonstrated that the release profile of CU and 5-FU from the nanoparticles in acidic conditions was more than the drug release in neutral conditions. In acidic conditions, due to faster degradation of nanoparticles, drugs are released faster. Moreover, these nanoparticles have high biocompatibility and potential in transporting CU and 5-FU drugs to HCT116 cells. The IC50 of co-delivery of CU and 5-FU was 65.42 mg/L, while, the IC50 value of drugs coated with nanoparticles (PCL-PEG-HA/FeCo/5-FU/Curcumin) was 72.26. Otherwise, utilizing nanoparticles can increase the amount of apoptosis compared to control and free 5-Fu and Curcumin.  In conclusion, PCL-PEG-HA/FeCo/5-FU/Curcumin nanoparticles can be an efficient solution in targeted drug delivery to colorectal cancer cells and reducing the side effects of these drugs on normal cells.

Toxoplasma gondii is a common parasite in the world. Pharmaceutical options for toxoplasmosis treatment are limited. Several studies have been conducted on the anti-infectious properties of miltefosine (MLF). We investigated the effectiveness of nanoemulsion miltefosine (NEM) in tachyzoites of T. gondii, RH strain. Various NEM formulations were designed considering pseudo-ternary phase diagrams. Physicochemical properties of the developed nanoemulsions (NEs), including pH, polydispersity index (PDI), droplet size, and refractive index (RI) were evaluated. The considered formulation was analyzed for dilution and stability tests. MTT assay was performed on Vero cells for calculation CC50 and on Vero cells with RH strain tachyzoite for calculation IC50. Sulfadiazine (SDZ) and pyrimethamine (PYR) were positive controls. The trypan blue method was used to investigate the effect of drugs (NEM, MLF, SDZ, PYR) in reducing the number of infected Vero cells and reducing the intracellular proliferation of tachyzoites. Next, the viability of tachyzoites was measured in the tube in the direct vicinity of different drug concentrations. The final particle size of NEM was calculated to be 17.463 nm by DLS and TEM. The CC50 of NEM (75.7 µg/mL) indicated lower toxicity than the other drugs. IC50 obtained by trypan blue, MTT, and test tube methods showed that NEM (28.43 µg/mL) has a suitable IC50 against Toxoplasma tachyzoites. The calculated selectivity index (SI) demonstrated that NEM (SI=2.66) is a more suitable drug candidate than the MLF and positive controls. The trypan blue assay indicated the excellent reduction effect of NEM on T. gondii intracellular proliferation rate and the number of infected cells.

Concerns regarding increased breast cancer cases worldwide have spurred interest in the discovery of novel approaches to overcome this deadly disease. Although several treatment strategies have been developed to treat breast cancer including chemotherapy, an efficient drug delivery system remains a challenge. Here, we study the drug distribution and boosting the efficiency of Panobinostat, a histone deacetylase inhibitor, by using silver nanoparticles as a controlled drug delivery system. Green synthesis of silver nanoparticles, as nanocarriers for drug delivery was synthesized by using Rhazya stricta extract and loaded with the drug. These drug-loaded nanoparticles were characterized by UV-vis spectroscopy, XRD, FTIR, SEM, and EDX techniques.  The AgNPs had an average size of 20 nm and were stable over a period. The evaluation of drug encapsulation effectiveness and drug release capacity revealed 56% encapsulation efficiency and sustained drug release. The kinetics study of drug release showed the first-order reaction which means that drug concentration is proportional to drug release. The MTT assay showed that drug-loaded AgNPs had a potent and dose-dependent anticancer activity on the breast cancer cell lines (MDA-MB-231).  As the successfully green synthesized Panobinostat-AgNPs were stable and exhibited increased in vitro anticancer activity compared with free Panobinostat, our data demonstrate that the combination of AgNPs with Panobinostat improves the drug’s long-term viability, effectiveness, and active targeting as a potential targeted therapeutic molecule for the treatment of cancer. To strengthen the utilization of this combination therapy in cancer therapy trials, further research is warranted in vivo.

Prescription of ibuprofen as a non-steroidal anti-inflammatory drug is limited by its gastrointestinal side effects and poor aqueous solubility. It was shown that phospholipid-association (PA) can lead to assembling assembly of the micellar form, thereby improving solubility  of non-steroidal anti-inflammatory drugs solubility and reducing their gastrointestinal side effects.  Ibuprofen in PA form was prepared and its interaction, crystallinity, and particle size were evaluated. Conventional ibuprofen and PA pellets in different drug contents were prepared by extrusion-spheronization. The mMorphology, shape factors, mechanical strength, and drug content of pellets were investigated. The dissolution test also was conducted in an intestinal-simulated medium and a gastric-simulated medium.  The results showed that PA micelles of ibuprofen were demonstrated to be formed, amorphous, and in an acceptable size range. Using a suitable composition of solid components and granulation fluid, pellets with desirable size, shape, and sphericity could be produced. All pellets have had plastic mechanical properties and the strength of formulations were  decreased with increasing PA ratio. The PA-pellet formulation had faster drug release compared to conventional ibuprofen pellets, via increasing ibuprofen solubility by reducing crystallinity in solid state and micelle formation in dissolution media. Moreover, ibuprofen solubility in a gastric-simulated medium was decreased and might result in reduced gastrointestinal side effects. Due to the demonstrated bioavailability advantages of PA-pellets, they can be considered for further studies.