A new approach for the treatment of Alzheimer's disease: insulin-quantum dots.

The potential use of insulin supplementation for Alzheimer's Disease (AD) was aimed to investigate and explore CQDs as an alternative delivery system. CQDs were produced by microwave and characterised. Insulin-loaded Ins-CQDs and in-situ Gel-Ins-CQDs were developed. The in vitro release kinetics, penetrations of insulin through excised sheep nasal mucosa were determined. Toxicity of CQDs were calculated on SH-SY5Y cells. The stability and usability of the prepared formulations were assessed. The insulin release from the solution was 70.75% after 3 hours, while it was 37.51% for in-situ Gel-Ins-CQDs. IC50 value was 52 µM. The mean particle diameters of Ins-CQDs and in-situ Gel-Ins-CQDs varied between 8.35 ± 0.19 to 8.75 ± 0.03 nm during a 6-month period. Zeta potentials ranged from -31.51 ± 1.39 to -24.43 ± 0.26 mV, and PDI values were between 9.8 ± 0.01 to 5.3 ± 3.2%(SD, n = 3) for Ins-CQDs and in-situ Gel-Ins-CQDs, respectively.Our results show that Gel-Ins-CQDs represented a controlled release over time and can be used for AD through the nasal route.

The combined use of carbon nanotubes with synthetic ceramics enhances posterolateral fusion: an experimental study in a rat spinal fusion model.

PURPOSE: The aim of the present study was to evaluate the effectiveness of carbon nanotubes (CNTs)/ HA-tricalcium phosphate (TCP) composite in a posterolateral spinal fusion model. METHODS: At first, CNTs and CNTs/HA-TCP composites were prepared. Twenty adult male Sprague Dawley rats were randomized into four groups with five rats in each group. Decortication was carried out in standard manner in all animals. Group 1 (only decortication), group 2 (CNTs), group 3 (HA-TCP) and group 4 (CNTs/HA-TCP) were formed. Eight weeks later, all animals were killed and obtained fusion segments were evaluated by manual palpation, histomorphometry and micro-computed tomography (mCT). RESULTS: In all evaluations, highest fusion values were obtained in Group 4. In mCT investigations, bone volume/ tissue volume (BV/TV) ratio was found to be significantly higher in composite group (group 4) only compared to ceramic group (group 3) (p < 0.001). Although in Group 2, in which only CNTs were used, the ratio was found to be statistically significantly higher than group 1(p < 0.001), the difference was not considered as significant in terms of fusion and in addition in group 2, CNTs were completely surrounded by fibrous tissue, i.e., no bone formation was observed. CONCLUSIONS: The CNTs/HA-TCP composite is a promising synthetic bone graft substitute for spinal fusion. Although CNTs are inadequate in producing spinal fusion when they are used alone, due to their high biocompatibility due to their high biocompatibility, and multiple effect on bone regeneration, they seem to increase fusion rates significantly when they are used in combination with ceramic-based synthetic grafts.

Nanodesigning of multifunctional quantum dots and nanoparticles for the treatment of fibrosarcoma.

An effective, dual drug(DD) loaded nanocarrier system (nano particle(NP), quantum dots(QDs)) having two active substances was aimed to develop for the treatment of fibrosarcoma. Zinc oxide(ZnO) QDs were produced using zinc acetate dehydrate as a precursor, were incorporated with chitosan(Ch), and finally decorated with PEG-linked folic acid and were found to be effective after imatinib mesylate(IM) and dexketoprofen trometamol(DT) were loaded. Characterisations, in vitro drug releases, cell toxicities, penetrations through cell lines and in-vivo animal tests of the prepared nanosystems were performed. The size of hybrid nanoparticles were 168.6 ± 48.8 nm, surface charge was -35.8 ± 0.26 mV. The encapsulation efficiency was 75% for IM and 99% for DT. DD-functionalised QDChNPs and lyophilised functionalised QDChNPs in capsules slowed down tumour growth by up to 76.5 and 88.7%. Our results demonstrate that developed hybrid nanoparticles are highly effective. This hybrid system gathers many of the advantages of nanotechnology into one form.

Can Carbon Quantum Dots (CQDs) or Boron Compounds be an Ultimate Solution for COVID-19 Therapy?

Severe acute respiratory syndrome (SARS) is an infectious and highly transmissible disease that is affected by SARS coronavirus (SARS-CoV) and for which there are presently no approved treatments. COVID-19 is a new strain of coronavirus that has not been previously identified in humans. It is also a member of the coronaviruse family and known to cause similar illnesses in humans. The last outbreak has been identified as a Pandemic because of COVID-19 infections in humans. This review has been prepared to give some information to readers or scientists about some new generation of boron-doped or boron attached composite quantum dots during the design phase of the drug or drug delivery systems to be developed to combat COVID-19 and to help in the design of new drugs and systems by opening some new horizons. All scientists and researchers must quickly share their ideas and experiences in the fight against COVID-19 to find a better therapy or strategy for humans, and thus we can be successful. In this sense, this review offers readers some new ideas and rational perspectives. In conclusion, boron-containing composite carbon quantum dots appear to be the most suitable delivery system for treating COVID-19 infections especially when they are delivered through the lung.

Development of controlled release dexketoprofen tablets and prediction of drug release using Artificial Neural Network (ANN) modelling

Dexketoprofen trometamol (DT) is an active S (+) enantiomer of ketoprofen, and a non-steroidal anti-inflammatory agent. DT has a short biological half-life and the dosing interval is quite short when there is a need to maintain the desirable effect for longer time periods. Consequently, a controlled release DT tablet was designed for oral administration aiming to minimize the number of doses and the possible side effects. Calculations of the parameters for controlled release DT tablets were shown clearly. Controlled release matrix-type tablet formulations were prepared using hydroxypropyl methylcellulose (HPMC) (low and high viscosity), Eudragit RS and Carbopol, and the effects of different polymers on DT release from the tablet formulations were investigated. The dissolution rate profiles were compared and analyzed kinetically. An Artificial Neural Network (ANN) model was developed to predict drug release and a successful model was obtained. Subsequently, an optimum formulation was selected and evaluated in terms of its analgesic and anti-inflammatory activity. Although the developed controlled release tablets did not have an initial dose, they were found to be as effective as commercially available tablets on the market. Dissolution and in vivo studies have shown that the prepared tablets were able to release DT for longer time periods, making the tablets more effective, convenient and more tolerable.

Anti-aging formulation of rosmarinic acid-loaded ethosomes and liposomes.

The study was aimed to evaluate the effectiveness of rosmarinic acid (RA) loaded ethosomes (ETHs) and liposomes (LPs) when subjected to the transdermal application. RA-loaded ETHs and LPs were prepared, optimised, and characterised. The ex vivo permeation studies of formulations using mouse abdominal skin were performed. Antioxidant activities and the inhibitory effects of formulations on collagenase and elastase enzymes were measured. Optimised ethosomal formulation (F3) was showed nanometric size range (138 ± 1.11 nm) and greatest entrapment (55 ± 1.80%), was selected for further transdermal permeation studies. Skin permeation profile of the nanoformulations analysed by HPLC revealed an enhanced permeation of ETHs. Transdermal flux of ETHs was found to be higher than RA solution and LPs. Enzyme inhibitions of ETHs were the significant difference found between ETHs and LPs (p < 0.05). ETHs were found to be more effective and successful than LPs. Results suggest that ETHs are more effective than LPs for transdermal delivery of RA.

Development of Orally Applicable, Combinatorial Drug-Loaded Nanoparticles for the Treatment of Fibrosarcoma.

Nanoparticulate systems have been receiving a significant attention especially for the treatment of cancer but one of the main hurdles is to produce these developed and high-tech nanosystems in large quantities. Anticancer drug formulations are generally designed for parenteral administrations but oral administration is still the most convenient route. In this study, orally applicable nano-sized chitosan nanoparticles (NPs) were successfully prepared using Nano Spray Dryer. It is possible to produce these NPs in large quantities by simply increasing the processing time using the machine without changing any parameter. A chemotherapeutic agent (imatinib mesylate; IMA) and nonsteroidal anti-inflammatory drug (dexketoprofen trometamol) were loaded together in these NPs. NPs were also functionalized with polyethylene glycol and folic acid to obtain long circulating NPs and tumor targeting. The antitumoral activities of formulations showed that these developed NPs can enhance the effectiveness. Animal experiments were performed on fibrosarcoma-bearing mice model, and the treatment with 0.8 mg/µL/kg IMA-loaded chitosan NPs was found to be successful to slow down the growth of tumors. The tumor tissues were removed from the animals and enzymatic activities were evaluated. The inhibitory effect of tyrosine kinase was found to be enhanced from 36.4% to 68.4% when IMA was used in combination with dexketoprofen trometamol. Furthermore, all dried NPs were found to be stable for more than a year at 25°C. Presented results show that these developed combinatorial drug-loaded NPs can be used for the treatment of fibrosarcoma, and these data can provide an insight, new strategies for productions or alternatives in cancer treatment.

Carbon nanotube membranes to predict skin permeability of compounds.

In the present study, carbon nanotube (CNT) membranes were prepared to predict skin penetration properties of compounds. A series of penetration experiments using Franz diffusion cells were performed with 16 different membrane compositions for model chemicals. Similar experiments were also carried out with same model molecules using five different commercially available synthetic membranes and human skins for the comparison. Model chemicals were selected as diclofenac, dexketoprofen and salicylic acid. Their permeability coefficients and flux values were calculated. Correlations between permeability values of model compounds for human skins and developed model membranes were investigated. Good correlations were obtained for CNT membrane, isopropyl myristate-treated CNT membrane (IM-CNT membrane) and bovine serum albumin-cholesterol, dipalmitoyl phosphatidyl choline-treated membrane (BSA-Cholesterol-DPPC-IM-CNT membrane). An artificial neural network (ANN) model was developed using some molecular properties and penetration coefficients from pristine CNT membranes to predict skin permeability values and quite good predictions were made.

Release Pattern of Liposomal Bupivacaine in Artificial Cerebrospinal Fluid.

OBJECTIVE: We aimed to compare the possible controlled release profile of multilamellar liposomal bupivacaine formulations with non-liposomal forms in artificial cerebrospinal fluid (CSF) under in vitro conditions. METHODS: Liposome formulations were prepared using a dry-film hydration method. Then, an artificial CSF-buffered solution was prepared. Bupivacaine base with liposomal bupivacaine base, bupivacaine HCl with liposomal bupivacaine HCl and bupivacaine HCl were added in a Franz diffusion cell. These solutions were kept in a hot water bath for 24 h. The samples were taken at 0.5, 1, 3, 6, 12 and 24 h (1st series of experiment). Solutions of bupivacaine base with liposomal bupivacaine base and bupivacaine HCl with liposomal bupivacaine HCl were centrifuged to obtain liposomal bupivacaine base and liposomal bupivacaine HCl. Afterwards, liposomal bupivacaine base and liposomal bupivacaine HCl were added in a Franz diffusion cell. After keeping these solutions in a hot water bath for 24 h as well, the samples were taken at the same time intervals (2(nd) series of experiment). All samples (54 from the 1st experiment and 36 from the 2(nd) experiment) were analysed with high-performance liquid chromatography and ultra-performance liquid chromatography and their chromatograms were obtained. RESULTS: After obtaining calibration curves for bupivacaine base and HCl, release patterns of these formulations were plotted. A markedly controlled slow-release pattern was observed for multilamellar liposomal bupivacaine than for non-liposomal bupivacaine in artificial CSF. CONCLUSION: Demonstration of controlled slow-release profile for mutilamellar liposomal bupivacaine in artificial CSF in vitro might support intrathecal use of liposomal bupivacaine in vivo in animal studies.

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).

Cheap, suitable, predictable and manageable nanoparticles for drug delivery: quantum dots.

Recently ZnO quantum dots are reported to be very promising for drug delivery. It has also been reported that adsorptive material can deliver drug molecules by simple adsorption and they release the drug at site of action by subsequent desorption. This has been shown for carbon nanotubes and some other hydrophobic molecules for transdermal applications in the literature. Therefore it was aimed to find the effect of ZnO quantum dots on transdermal penetrations of selected model drug molecules (ketoprofen and dexketoperofen). Drug coated ZnO quantum dots were found to increase transdermal penetration of ketoprofen and dexketoprofen through rat skin.

A feasible way to use carbon nanotubes to deliver drug molecules: transdermal application.

INTRODUCTION: Nanotechnology has gained increasing importance in the pharmaceutical and medical fields, beyond its importance in physics and technology. Targeting of the drug or active molecules can be achieved rather easily with some nanocarriers because of their unique properties; to program or control of delivery can also be possible. One of the smart nanosystems is carbon nanotubes (CNTs) because they are elecroconductive and they have very big surface area to deliver active molecules. There have been many drug delivery systems proposed to the scientific world using CNTs. One administration way which appears to be the most appropriate for drug delivery is transdermal application. AREAS COVERED: Performed experiments and proposed techniques with the use of CNTs are scrutinized and discussed in this review. EXPERT OPINION: In the light of current knowledge, a feasible way to use CNTs to deliver drug molecules is transdermally.

Development of sustained release formulation of an antithrombotic drug and application of Fuzzy logic.

Clopidogrel bisulphate has quite low bioavailability (40-50%). It was aimed to increase its bioavailability by designing a controlled release dosage form of clopidogrel, which is different from available current dosage forms in the market. There are also some attempts to overcome patent protection of clopidogrel by combination of active substances or preparation of controlled release tablets. Therefore, it was also aimed to determine in vitro and in vivo properties of controlled release clopidogrel tablets. The amounts of releases from formulations were subjected computer program and effects of components in the formulation on release were investigated (INFORM v.3.7 and FORMRULES, Intelligensys Ltd). Two sustained release formulations and innovator product were selected and their effectiveness was compared by in vivo tests in rabbits. In conclusion, proposed controlled release formulations were found to be an alternative and to be more effective for longer periods than the commercial one.

Carbon nanotubes for transdermal drug delivery.

In this study, drug carrier properties through skin and penetration enhancement effects of carbon nanotubes (CNTs) are presented. Multi-walled and double-walled carbon nanotubes were used. Penetration enhancement into the skin following passive diffusion and iontophoresis were determined. Possible solubility enhancement effects and drug adsorption properties of CNTs were investigated. CNTs were found to be a useful drug carrier system and they can provide a high loading and enhanced transdermal penetration for especially hydrophobic drugs. The electroconductive nature of CNTs allows easy application of iontophoresis and the additional advantage of CNTs appears to be using them as electrodes.

Carbon nanotubes to deliver drug molecules.

Nanotechnology is rapidly developing field in especially engineering and medical sciences. Carbon nanotubes are one of the most studied nanomaterials in material sciences and physics. Although there are limitted number of studies have been performed with carbon nanotubes in medical sciences and pharmacy, to use carbon nanotubes as drug delivery material is still at beginning and at developing stage. Carbon nanotubes are adsorptive materials and they can actively adsorb drug molecules on the surface. In this study the adsorption properties of carbon nanotubes were investigated for ibuprofen, naproxen, oxaliplatin and paclitaxel. Desorption properties and the posibility of using them as drug delivery systems for mentioned drugs were investigated and determined. Multiwalled carbon nanotubes were also PEGylated and PEGylation was found to be successful and effective. Particle sizes and zeta potentials of carbon nanotubes were not altered after PEGylation.

Determination of the sildenafil effect on alopecia areata in childhood: An open-pilot comparison study.

BACKGROUND: Alopecia areata is an immunologically mediated cessation of hair growth primarily involving, but not limited to, the scalp. The treatment of alopecia areata involves promotion of hair growth (for instance with topical minoxidil application), immunosuppression (intralesional or systemic steroid therapy, phototherapy) or immunomodulation (anthralin, dinitrochlorobenzene, diphenylcyclopropenone, squaric acid dibutylester). All these medications have some disadvantages and difficulties for the treatment of children with alopecia areata. OBJECTIVE: To use an open-pilot study to assess the efficacy of topical 1% sildenafil in children diagnosed with alopecia areata. METHODS: Eight patients with (25% of scalp surface area involvement) alopecia areata who were refractory to previous topical treatments applied 1% sildenafil twice daily for 3 months. All the patients completed the study. RESULTS: Two patients experienced vellus-type hair growth and one patient had terminal hair growth. However, these outcomes were accepted as the spontaneous regression of the disease. CONCLUSION: We cannot recommend the use of topical 1% sildenafil for the treatment of alopecia areata without further evidence of its therapeutic benefit.

Reverse iontophoresis: a non-invasive technique for measuring blood urea level.

Monitoring of the urea level of patients with insufficient kidney function requires repetitive blood sampling. The potentially painful nature of blood sampling and the difficulty of venous access, particularly in premature neonates, as well as possible complications of needle injuries, create many disadvantages. A non-invasive technique needs to be developed for monitoring the urea level for these patients. Reverse iontophoresis has recently gained importance and the possibility of extracting some compounds from body fluids using reverse iontophoresis has been reported in the literature. Moreover, a small, watch-type device has been developed for the determination of blood glucose levels using a similar approach. The aim of the current study was to investigate the possibility of extracting urea from blood through skin using reverse iontophoresis to monitor blood urea levels without taking a blood sample. In vitro iontophoresis studies have indicated that urea may be successfully transferred through the full thickness of human skin. The reverse iontophoresis technique was applied to 17 patients with kidney insufficiency and urea was successfully extracted through their skin into the collection solution. A high correlation ( r(2)=0.878) between urea concentrations in collection solutions and urea levels in the blood was observed. These results suggest that it is possible to make a watch-type device for monitoring blood urea levels.

Transdermal administration of bromocriptine.

Bromocriptine (BRC) has been mainly used for the inhibition of lactation, treatment of menstrual disorders, Parkinson disease, breast tumours, infertility and brain tumours as a dopamine agonist in clinics. But current BRC formulations have some side effects and bioavailability problems because of hepatic first pass effect. Transdermal application could be an alternative route to overcome all these problem and penetration properties of BRC has not been studied yet. Therefore, it was aimed to investigate the effectiveness of transdermal formulation of BRC which is applicable to the skin. For this purpose, a number of BRC gel formulations (Carbopol-934 (C-934), chitosan (CH) and Gantrez-SP215 (G-SP215) were developed and the effectiveness and bioavailability of the formulations were compared in rabbits. Commercial BRC tablets (Parlodel) were also given to rabbits orally and plasma levels were compared. The effects of two different penetration enhancers, sodium taurocholate (ST) and ethoxydiglycol-Transcutol) (TR) on the BRC penetration were also investigated. The skin samples from the dorsal part of the rabbit were removed after CH gel application and investigated under electron microscope to understand the effects of the gel on the penetration and the possible penetration mechanisms through skin were also discussed. In conclusion, CH gel formulation was found to be the best formulation and comparable blood BRC concentrations were obtained when applied to the rabbit skin. Higher blood levels were obtained with the use of CH. The main penetration process was found to be through transcellular route but some other mechanisms were also found to be incorporated, after microscopic investigation. CH gel was found to be a useful carrier for BRC administration through dermal route and the penetration enhancing effect and the mechanism of CH gel were first established in this study. It was concluded that transdermal delivery of BRC may be a very promising alternative route to the oral route for the treatment.