In-situ forming biodegradable implants for sustained Fluocinolone acetonide release to the posterior eye: In-vitro and in-vivo investigations in rabbits.

Delivering medication to the posterior segment of the eye presents a significant challenge. Intravitreal injection has emerged as the preferred method for drug delivery to this area. However, current injectable non-biodegradable implants for fluocinolone acetonide (FA) require surgical removal after prolonged drug release, potentially affecting patient compliance. This study aimed to develop an in-situ forming biodegradable implant (ISFBI) optimal formulation containing PLGA504H and PLGA756S (50:50 w/w%) with the additive NMP solvent. The goal was to achieve slow and controlled release of FA over a two-month period with lower burst release, following a single intravitreal injection. Through morphology, rheology, stability and in-vitro release evaluations, the optimal formulation demonstrated low viscosity (0.12-1.25 Pa. s) and sustained release of FA at a rate of 0.36 µg/day from the third day up to two months. Furthermore, histopathology and in-vivo studies were conducted after intravitreal injection of the optimal formulation in rabbits' eye. Pharmacokinetic analysis demonstrated mean residence time (MRT) of 20.02 ± 0.6 days, half-life (t1/2) of 18.80 ± 0.4 days, and clearance (Cl) of 0.29 ± 0.03 ml/h for FA in the vitreous humor, indicating sustained and slow absorption of FA by the targeted retinal tissue from vitrea over the two-month period and eliminating through the anterior section of the eye, as revealed by its presence in the aqueous humor. Additionally, FA exhibited no detection in the blood and no evidence of systemic side effects or damage on the retinal layer and other organs. Based on these findings, it can be concluded that in-situ forming injectable biodegradable PLGA implants can show promise as a long-acting and controlled-release system for intraocular drug delivery.

Formulation and optimization of a single-layer coat for targeting budesonide pellets to the descending Colon.

The current budesonide formulations are inadequate for addressing left-sided colitis, and patients might hesitate to use an enema for a prolonged time. This study focuses on developing a single-layer coating for budesonide pellets targeting the descending colon. Pellets containing budesonide (1.5%w/w), PVP K30 (5%w/w), lactose monohydrate (25%w/w) and Avicel pH 102 (68.5%w/w) were prepared using extrusion spheronization technique. Coating formulations were designed using response surface methodology with pH and time-dependent Eudragits. Dissolution tests were conducted at different pH levels (1.2, 6.5, 6.8, and 7.2). Optimal coating formulation, considering coating level and the Eudragit (S + L) ratio to the total coating weight, was determined. Budesonide pellets were coated with the optimized composition and subjected to continuous dissolution testing simulating the gastrointestinal tract. The coating, with 48% S, 12% L, and 40% RS at a 10% coating level, demonstrated superior budesonide delivery to the descending colon. Coated pellets had a spherical shape with a uniform 30 µm thickness coating, exhibiting pH and time-dependent release. Notably, zero-order release kinetics was observed for the last 9 h in colonic conditions. The study suggests that an optimized single-layer coating, incorporating pH and time-dependent polymers, holds promise for consistently delivering budesonide to the descending colon.

Sustain-release lipid-liquid crystal formulations of pexiganan against Helicobacter pylori infection: in vitro evaluation in C57BL/6 mice.

INTRODUCTION: The Gram-negative bacterium Helicobacter pylori, H. pylori, is associated with significant digestive disorders. However, the effectiveness of bacterial eradication is declining due to drug resistance. A potent anti-H. pylori activity is shown by the natural antimicrobial peptide pexiganan. OBJECTIVE: The current study aimed to evaluate the effectiveness of pexiganan and its lipid-liquid crystals (LLCs) in inducing Helicobacter pylori in mice. METHODS: In this experimental study, H. pylori infection was first induced in C57BL/6 mice. Secondly, the antibacterial efficacy of pexiganan and its LLCs formulations was investigated to eliminate H. pylori infection. RESULTS: The H. pylori infection could not be completely eradicated by pexiganan peptide alone. However, incorporating pexiganan within the LLC formulation resulted in an increased elimination of H. pylori. Under the H&E strain, the pexiganan-LLCs formulation revealed minimal mucosal alterations and a lower amount of inflammatory cell infiltration in the stomach compared to the placebo. CONCLUSION: Clarithromycin was more effective than pexiganan at all tested concentrations. Furthermore, the pexiganan-loaded LLCs exhibited superior efficacy in curing H. pylori infection in a mouse model compared to pexiganan alone. This formulation can enhance H. pylori clearance while mitigating the adverse effects, typically associated with conventional drugs, leading to a viable alternative to current treatment options.

Microfluidic-assisted preparation of PLGA nanoparticles loaded with insulin: a comparison with double emulsion solvent evaporation method.

Poly lactic-co-glycolic acid (PLGA) is an ideal polymer for the delivery of small and macromolecule drugs. Conventional preparation methods of PLGA nanoparticles (NPs) result in poor control over NPs properties. In this research, a microfluidic mixer was designed to produce insulin-loaded PLGA NPs with tuned properties. Importantly; aggregation of the NPs through the mixer was diminished due to the coaxial mixing of the precursors. The micromixer allowed for the production of NPs with small size and narrow size distribution compared to the double emulsion solvent evaporation (DESE) method. Furthermore, encapsulation efficiency and loading capacity indicated a significant increase in optimized NPs produced through the microfluidic method in comparison to DESE method. NPs prepared by the microfluidic method were able to achieve a more reduction of trans-epithelial electrical resistance values in the Caco-2 cells compared to those developed by the DESE technique that leads to greater paracellular permeation. Compatibility and interaction between components were evaluated by differential scanning calorimetry and fourier transform infrared analysis. Also, the effect of NPs on cell toxicity was investigated using MTT test. Numerical simulations were conducted to analyze the effect of mixing patterns on the properties of the NPs. It was revealed that by decreasing flow rate ratio, i.e. flow rate of the organic phase to the flow rate of the aqueous phase, mixing of the two streams increases. As an alternative to the DESE method, high flexibility in modulating hydrodynamic conditions of the microfluidic mixer allowed for nanoassembly of NPs with superior insulin encapsulation at smaller particle sizes.

Development of Sustained Release Formulations Based on Lipid-Liquid Crystal to Control the Release of Deoxycholate: In Vitro and In Vivo Assessment.

Subcutaneous injections of phosphatidylcholine (PC), sodium deoxycholate (NADC), and a mixture of them were found to be an effective option for treating cellulite. However, it is noteworthy that the injection of NADC may result in inflammation as well as necrosis in the injection area. The preparation of a sustained release formulation based on lipid-liquid crystal that controls the release of NADC could be a potential solution to address the issue of inflammation and necrosis at the site of injection. To present a practical and validated approach for accurately determining the concentration of NADC in LLC formulations, spectrofluorimetry was used based on the International Council for Harmonization (ICH) Q2 guidelines. Based on the validation results, the fluorometric technique has been confirmed as a reliable, efficient, and economical analytical method for quantifying NADC concentrations. The method demonstrated favorable attributes of linearity, precision, and accuracy, with an r2 value of 0.999. Furthermore, it exhibited excellent interday and intraday repeatability, with RSD values below 4%. The recovery percentages ranged from 97 to 100%, indicating the method's ability to accurately measure NADC concentrations. The subcutaneous injection of the LLC-NADC demonstrated a reduction in inflammation and tissue necrosis in skin tissue, along with an increase in fat lysis within 30 days, when compared to the administration of only NADC solution. Moreover, the histopathological assessment confirmed that the use of the LLC formulation did not result in any detrimental side effects for kidney or heart tissue.

Preparation and characterization of solid lipid nanoparticles encapsulated noscapine and evaluation of its protective effects against imiquimod-induced psoriasis-like skin lesions.

Psoriasis is a chronic inflammatory skin disease characterized by thickening the epidermis with erythema, scaling, and proliferation. Noscapine (NOS) has several anti-inflammatory, anti-angiogenic, and anti-fibrotic effects, but its low solubility and large size results in its lower efficacy in the clinic. In this regard, solid lipid nanoparticles (SLN) encapsulated NOS (SLN-NOS) were fabricated using the well-known response surface method based on the central composite design and modified high-shear homogenization and ultrasound method. As a result, Precirol® was selected as the best lipid base for the SLN formulation based on Hildebrand-Hansen solubility parameters, in which SLN-NOS 1 % had the best zeta potential (-35.74 ± 2.59 mV), average particle size (245.66 ± 17 nm), polydispersity index (PDI, 0.226 ± 0.09), high entrapment efficiency (89.77 %), and ICH-based stability results. After 72 h, the SLN-NOS 1 % released 83.23 % and 58.49 % of the NOS at pH 5.8 and 7.4, respectively. Moreover, Franz diffusion cell's results indicated that the skin levels of NOS for SLN and cream formulations were 46.88 % and 13.5 % of the total amount, respectively. Our pharmacological assessments revealed that treatment with SLN-NOS 1 % significantly attenuated clinical parameters, namely ear thickness, length, and psoriasis area and severity index, compared to the IMQ group. Interestingly, SLN-NOS 1 % reduced the levels of interleukin (IL)-17, tumor necrosis factor-α, and transforming growth factor-ß, while elevating IL-10, compared to the IMQ group. Histology studies also showed that topical application of SLN-NOS 1 % significantly decreased parakeratosis, hyperkeratosis, acanthosis, and inflammation compared to the IMQ group. Taken together, SLN-NOS 1 % showed a high potential to attenuate skin inflammation.

Surface-modified cationic liposomes with a matrix metalloproteinase-degradable polyethylene glycol derivative improved doxorubicin delivery in murine colon cancer.

PEGylation is a commonly used approach to prolong the blood circulation time of cationic liposomes. However, PEGylation is associated with the "PEG dilemma", which hinders binding and uptake into tumor cells. The cleavable PEG products are a possible solution to this problem. In the current research, doxorubicin-loaded cationic liposomes (Dox-CLs) surface-conjugated with a matrix metalloproteinase-2 (MMP-2)-sensitive octapeptide linker-PEG derivative were prepared and compared to non-PEGylated and PEGylated CLs in terms of size, surface charge, drug encapsulation and release, uptake, in vivo pharmacokinetics, and anticancer efficacy. It was postulated that PEG deshielding in response to the overexpressed MMP-2 in the tumor microenvironment increases the interaction of protected CLs with cellular membranes and improves their uptake by tumor cells/vasculature. MMP2-responsive Dox-CLs had particle sizes of ∼115-140 nm, surface charges of ∼+25 mV, and encapsulation efficiencies of ∼85-95%. In vitro cytotoxicity assessments showed significantly enhanced uptake and cytotoxicity of PEG-cleavable CLs compared to their non-cleavable PEG-coated counterparts or Caelyx®. Also, the chick chorioallantoic membrane assay showed great antiangiogenesis ability of Dox-CLs leading to target and prevent tumor neovascularization. Besides, in vivo studies showed an effective therapeutic efficacy of PEG-cleavable Dox-CLs in murine colorectal cancer with negligible hematological and histopathological toxicity. Altogether, our results showed that MMP2-responsive Dox-CLs could be served as a promising approach to improve tumor drug delivery and uptake.

The recent insight in the release of anticancer drug loaded into PLGA microspheres.

Cancer is a series of diseases leading to a high rate of death worldwide. Microspheres display specific characteristics that make them appropriate for a variety of biomedical purposes such as cancer therapy. Newly, microspheres have the potentials to be used as controlled drug release carriers. Recently, PLGA-based microspheres have attracted exceptional attention relating to effective drug delivery systems (DDS) because of their distinctive properties for a simple preparation, biodegradability, and high capability of drug loading which might be increased drug delivery. In this line, the mechanisms of controlled drug release and parameters that influence the release features of loaded agents from PLGA-based microspheres should be mentioned. The current review is focused on the new development of the release features of anticancer drugs, which are loaded into PLGA-based microspheres. Consequently, future perspective and challenges of anticancer drug release from PLGA-based microspheres are mentioned concisely.

Preparation and Evaluation of the In situ Gel-forming Chitosan Hydrogels for Nasal Delivery of Morphine in a Single Unit dose in Rats to Enhance the Analgesic Responses.

INTRODUCTION: In this study, an in situ gel-forming chitosan hydrogel was prepared with the use of glutamate salt of chitosan (Ch-Ga), ß-glycerophosphate (Gp), and morphine (Mor). The paper is focused on in vitro physicochemical properties and in-vivo analgesic effects of the prepared chitosan hydrogel. METHOD: The thermosensitive properties of prepared chitosan hydrogel were evaluated during the different temperatures and times. The physicochemical properties of chitosan hydrogel were investigated by infrared (IR) spectroscopy and X-ray diffraction analysis (XRD). Also, its cell cytotoxicity effects were evaluated in murine NIH/3T3 normal cells. Subsequently, the distribution of chitosan hydrogel in the nasal cavity of rats and its analgesic responses were evaluated. The prepared chitosan hydrogel showed that it could be gelled at the temperature of 34 °C before leaving the nose in the shortest possible time of 30 s. RESULT: The analgesic responses of the intranasal (IN) injection of chitosan hydrogel (IN-chitosan hydrogel, 10 mg Mor/kg) in a single unit dose in rat relative to the placebo and intranasal or intraperitoneal (IP) injection of free morphine solution (IN-Free Mor or IP-Free Mor, 10 mg Mor/kg) via the hot plate test, reveal that the IN-chitosan hydrogel could induce fast analgesic effects of morphine with maximum possible effect (MPE) of 93% after 5 min compare to the IN-Free Mor and IP-Free Mor with MPE of 80% after 15 min and 66% after 30 min, respectively. Also, prolonged analgesic effects with MPE of 78 % after 6 h of injection were only seen in the IN-chitosan hydrogel injected group. The obtained fluorescent images of rat's brain injected with IN-chitosan hydrogel containing doxorubicine (Dox) as a fluorescent agent showed that the mucosal adhesive and absorption enhancer properties of IN-chitosan hydrogel resulting in longer presence of them in the nasal cavity of rats followed by more absorption of Dox from the blood vessels of olfactory bulbs with a 74% color intensity compared to the IN-Free Mor and IN-Free Dox with 15%. CONCLUSION: These data reveal that the IN-chitosan hydrogel could induce fast and prolonged analgesic effects of morphine compare to the IN/IP-Free Mor, which could be considered as an in situ gel-forming thermosensitive chitosan hydrogel for nasal delivery of wide ranges of therapeutic agents.

Preparation and Characterization of Undecylenoyl Phenylalanine Loaded-Nanostructure Lipid Carriers (NLCs) as a New α-MSH Antagonist and Antityrosinase Agent.

Purpose: The aim of this study was to characterize the undecylenoyl phenylalanine (Sepiwhite (SEPI))-loaded nanostructured lipid carriers (NLCs) as a new antimelanogenesis compound. Methods: In this study, an optimized SEPI-NLC formulation was prepared and characterized for particle size, zeta potential, stability, and encapsulation efficiency. Then, in vitro drug loading capacity and the release profile of SEPI, and its cytotoxicity were investigated. The ex vivo skin permeation and the anti-tyrosinase activity of SEPI-NLCs were also evaluated. Results: The optimized SEPI-NLC formulation showed the size of 180.1±5.01 nm, a spherical morphology under TEM, entrapment efficiency of 90.81±3.75%, and stability for 9 months at room temperature. The differential scanning calorimetry (DSC) analysis exhibited an amorphous state of SEPI in NLCs. In addition, the release study demonstrated that SEPI-NLCs had a biphasic release outline with an initial burst release compared to SEPI-EMULSION. About 65% of SEPI was released from SEPI-NLC within 72 h, while in SEPI-EMULSION, this value was 23%. The ex vivo permeation profiles revealed that the higher SEPI accumulation in the skin following application of SEPI-NLC (up to 88.8%) compared to SEPI-EMULSION (65%) and SEPI-ETHANOL (74.8%) formulations (P<0.01). An inhibition rate of 72% and 65% was obtained for mushroom and cellular tyrosinase activity of SEPI, respectively. Moreover, results of in vitro cytotoxicity assay confirmed SEPI-NLCs to be non-toxic and safe for topical use. Conclusion: The results of this study demonstrate that NLC can efficiently deliver SEPI into the skin, which has a promise for topical treatment of hyperpigmentation.

Prolonged local delivery of doxorubicin to cancer cells using lipid liquid crystalline system.

Exploring efficient strategies to eradicate the tumor tissue and enhance patient outcomes still remained a serious challenge. Systemic toxicity of the current chemotherapeutics and their low concentration in the tumor site limited reaching a practical approach in their administration and combinational therapy. Besides, complicated delivery platforms could not receive the marketing approval due to difficulties in scale up procedures. To this aim, we developed a simple injectable local delivery platform which provided a sufficient dose of the chemotherapeutic in the cancerous tissue with sustained release properties. Herein, various injectable in situ forming LLC formulations loaded with doxorubicin (DOX) were developed. Although there were many previous studies on lipid liquid crystal (LLC) based formulations, their performance as an injectable intratumoral depot system for local chemotherapy has not been extensively investigated yet. In the current study we developed 18 formulations of DOX loaded LLCs using Box-Behnken method via different ratios of phosphatidyl choline: sorbitan monooleate (PC: SMO), N-Methyl-2-pyrrolidone (NMP), and tween 80. The physicochemical properties of the formulations were investigated and their in vivo tumor inhibition efficiencies in C26 tumor bearing mouse model was further studied. The results indicated that DOX loaded PC: SMO/NMP/Tween 80 (50:50/50/2 w/w%) and DOX loaded PC: SMO/NMP (50:50/50 w/w%) formulations were syringeable with pseudoplastic behavior. Also, they could release the cargo in a sustained manner for 60 days. Compared to intravascular administration of DOX, intratumoral injection of the developed formulations led to a significant decrease in tumor volume and enhancement of the survival rate in murine tumor model. Additionally, animal imaging studies proved their prolonged accumulation in the tumor site. Histopathological studies showed that treatment with the DOX-loaded LLC formulations did not cause any systemic toxicity to vital organs. Taken together, we believe that the developed simple and efficient local delivery platform can be further used in combinational therapies and treatment of various solid tumors.

Injectable In-Situ Forming Depot Based on PLGA and PLGA-PEG-PLGA for Sustained-Release of Risperidone: In Vitro Evaluation and Pharmacokinetics in Rabbits.

In the current research, novel drug delivery systems based on in situ forming gel (ISFG) (PLGA-PEG-PLGA) and in situ forming implant (ISFI) (PLGA) were developed for one-month risperidone delivery. In vitro release evaluation, pharmacokinetics, and histopathology studies of ISFI, ISFG, and Risperdal CONSTA® were compared in rabbits. Formulation containing 50% (w/w %) of PLGA-PEG-PLGA triblock revealed sustained release for about one month. Scanning electron microscopy (SEM) showed a porous structure for ISFI, while a structure with fewer pores was observed in the triblock. Cell viability in ISFG formulation in the first days was more than ISFI due to the gradual release of NMP to the release medium. Pharmacokinetic data displayed that optimal PLGA-PEG-PLGA creates a consistent serum level in vitro and in vivo through 30 days, and histopathology results revealed nearly slight to moderate pathological signs in the rabbit's organs. The shelf life of the accelerated stability test didn't affect the results of the release rate test and demonstrated stability in 24 months. This research confirms the better potential of the ISFG system compared with ISFI and Risperdal CONSTA®, which would increase patients' compliance and avoid problems of further oral therapy.

Simultaneous determination of mometasone furoate and calcipotriol in a binary mixture by validated HPLC and chemometric-assisted UV spectrophotometric methods and identification of degradation products by LC-MS.

Objectives: A new binary mixture containing mometasone furoate (MF) and calcipotriol (CP) is suggested to manage psoriasis; since the combined stability profile of these drugs is poorly understood. Materials and Methods: Herein MF, CP, and their mixtures were subjected to various stress conditions. Also, stability-indicating HPLC was developed and validated according to ICH guidelines with Box-Behnken design. The degradation products (DPs) were predicted in silico and identified using LC-MS. The bioactivity and toxicity of DPs were studied using molecular docking and alamarBlue assay, respectively. Spectroscopic techniques of the first derivative, first-derivative ratio, and the mean-centering of ratio spectra were also used to determine MF and CP in the mixture because of spectra overlapping. Results: The major degradants for MF in alkaline conditions were DP1, DP2, and DP3, while in thermal and UV conditions, only DP1 was generated. CP gave one degradant in all conditions. No new impurity was observed in the MF and CP mixtures. The results of spectrophotometry showed good linearity in the range of 4-50 and 2-20 µg/ml, while linearity for HPLC was in the range of 4-50 and 0.5-2.5 µg/ml for MF and CP, respectively. Recovery was 99.61-100.38% for UV and 100.4% for HPLC methods of MF and 100.6-101.4% for UV and 99.5% for HPLC methods of CP. Conclusion: The developed methods can be used as simple, accurate, precise, and rapid techniques for routine quality control of MF and CP mixtures.

The recent advancement in the PLGA-based thermo-sensitive hydrogel for smart drug delivery.

To date, hydrogels have opened new prospects for potential applications for drug delivery. The thermo-sensitive hydrogels have the great potential to provide more effective and controllable release of therapeutic/bioactive agents in response to changes in temperature. PLGA is a safe FDA-approved copolymer with good biocompatibility and biodegradability. Recently, PLGA-based formulation have attracted a lot of interest for thermo-sensitive hydrogels. Thermo-sensitive PLGA-based hydrogels provide the delivery system with good spatial and temporal control, and have been widely applied in drug delivery. This review is focused on the recent progression of the thermo-sensitive and biodegradable PLGA-based hydrogels that have been reported for smart drug delivery to the different organs. Eventually, future perspectives and challenges of thermo-sensitive PLGA-based hydrogels are discussed briefly.

Preparation of porous PCL-PEG-PCL scaffolds using supercritical carbon dioxide.

In this study, the Supercritical Carbon Dioxide (scCO2) gas foaming procedure was used in the preparation of scaffolds containing the model drug dexamethasone (DXMT). The method used did not include an organic solvent thus making it a safe method. The ring-opening polymerization of PCL-PEG-PCL (PCEC) triblock was conducted using an organocatalyst [1,8 diazabicyclo [5.4.0] undec-7-ene (DBU)]. After mixing 5.0 g of DXMT with 50.0 g of PCEC, hydraulic pressure was applied to compress the mixed powder into disc-like tablets. The tablet-like scaffold of the triblock containing DXMT was inserted into a scCO2 gas-foaming device. The peak porosity percentage of the synthesized triblock was found to be 55.58 %. Pressure, temperature, soaking time and the time required to depressurize were recorded as 198 bar, 50 °C, 2.0 h, and 28 min respectively. After treatment with scCO2, the scaffolds experienced an almost full release of DXMT in vitro after 30 days (83.74 ± 1.54 % vs 52.24 ± 2.03 % before scCO2 treatment). In conclusion, the results proved that the scCO2 gas foaming procedure could be employed for constructing modifiable PCEC scaffolds with plausible porosity and structural and morphological features which can manipulate drug release.

In-vitro and in-vivo evaluation of sustained-release buprenorphine using in-situ forming lipid-liquid crystal gels.

AIMS: Sustained-release systems reduce the incidence of drug side effects and the need for frequent drug consumption, thus increasing patient compliance with treatment. In this study, we aimed to produce sustained-release buprenorphine (BP) using lipid-liquid crystal gels. MAIN METHODS: The three experimental groups in this study included: group I: lipid-liquid crystal formulation 5 (F5) containing BP, group II: BP-free F5, group III: BP solution in NMP, and group IV: control (no treatment). The formulations were injected subcutaneously into the rabbits' back neck. KEY FINDINGS: The results showed that the time required to reach the drug's maximum concentration (Tmax) was longer in group I than in group III. The maximum BP concentration (Cmax) and the constants of the drug removal rate and drug absorption rate (Ka) were significantly higher in group III compared to group I. The half-life (t1/2) of the drug in blood circulation was significantly longer in group I than in group III. Histopathological analysis revealed no histological abnormalities in the skin and heart in group I (BP-containing F5); however, mild hyperemia was observed in interstitial vessels in group III (BP-containing NMP). The kidney and liver tissues showed normal structure in the control group, as well as groups I and II. However, in the group receiving BP-containing NMP, significant congestion, tissue damage, necrosis, and fibrosis were observed in the kidney and liver. SIGNIFICANCE: The results showed that the lipid-liquid crystal system can be used to design slow-release platforms for BP, minimizing the side effects associated with the use of its conventional forms.

Recent progress in the graphene-based biosensing approaches for the detection of Alzheimer's biomarkers.

Alzheimer's disease (AD) is one of the most common types of neurodegenerative disorders. It is possible to identify AD early thanks to the measurement of specific biomarker levels. Owing to crucial roles of biomarkers in the AD, the detection of AD-related biomarkers may be suitable for predictive identification of AD. Biosensors is a novel tool that could be beneficial to appreciate recognition of several AD biomarkers as early as possible. Graphene and its derivatives containing graphene oxide (GO) and reduced-GO (rGO) can be good choice for biosensing approaches due to their unique properties. GO/rGO-based biosensors or nanosensors have been widely used for the determination of AD biomarkers. In this article, the general aspects of AD, its biomarkers, biosensors, and GO are overviewed. In addition, this review provides the current developments in the applications of graphene-based biosensors for recognition of AD biomarkers. Future perspectives and challenges of graphene-based biosensing as a new approach for detection of AD are discussed in brief as well.

Supercritical CO2 versus water as an antisolvent in the crystallization process to enhance dissolution rate of curcumin.

Antisolvent crystallization approach using either water (in conventional crystallization process (WAS)), or supercritical CO2 (in supercritical anti-solvent crystallization (SCAS)), was employed in presence of hydroxypropyl methylcellulose (HPMC) to enhance the dissolution of curcumin. The impact of pressure, temperature and depressurization time on the SCAS process was studied using the Box-Behnken design to achieve the highest saturation solubility. A physical mixture of curcumin-HPMC was prepared for comparison purposes. Saturation solubility, scanning electron microscopy, differential scanning calorimetry, X-ray diffraction analysis and Fourier transform infrared spectroscopy were conducted to characterize the solid-state characteristics of the crystallized samples. Dissolution studies helped in ascertaining the effects of the crystallization techniques on the performance of the formulation. Curcumin crystalized by different antisolvent displayed varied shapes, sizes, saturation solubility's and dissolution properties. In SCAS process, the maximum saturation solubility (2.83 µg/mL) was obtained when the pressure, temperature and depressurization time were 275 bars, 55 °C, and 22 min respectively. The SCAS samples showed the highest dissolution (70%) in 30 min compared to WAS (27%), physical mixture (18%) and unprocessed curcumin (16%). The improved dissolution rate of SCAS sample originates from the development of sponge-like particles with augmented porosity, decreased crystallinity as well as increased solubility of curcumin.

The effects of Ziziphus Spina leaves' Hydro-Alcoholic Extract Vaginal Cream and Clotrimazole on Candida albicans in Wistar Rats.

Background: In vitro, Ziziphus Spina-Christi (ZSC) leaves have been shown to have antimicrobial and antifungal effects. This study aimed to examine the effects of Ziziphus Spina leaves hydro-alcoholic extracts with Clotrimazole against Candida albicans in female rats. Methods: Four groups of rats were infected vaginally with C. Albicans, and 1 group not infected was considered negative control. The infected groups received the following treatments: 2 groups were treated with vaginal 5%, or 10%, of Ziziphus Spina extract creams. One group received 1% clotrimazole, and 1 group did not receive any treatment considered a positive control. Results: The mean number of colony-forming units (CFUs) before the intervention was 195.83 ± 395.126 in the 5% ZSC group, 346.33 ± 396.719 in the 10% ZSC group, 345.17 ± 507.431 in the clotrimazole group, 212.20 ± 148.304 in the positive control group (P = .604), and 0 in the negative control group (P = .003). After 1 week, the average number of CFUs considerably dropped to 65.14 ± 36.03 in the 5% ZSC group, 1.43 ± 3.60 in the 10% ZSC group, and 0.43 ± 1.13 in the clotrimazole group. The number in the positive control group remained unchanged (212.20 ± 148.304) (P = .005). After 2 weeks, the average number of CFUs was 0 in the 10% ZSC group, Clotrimazole and negative control groups and was 4.57 ± 23.99 in the 5% ZSC group (P < .001). Conclusions: Our findings indicated that the effectiveness of Vaginal creams containing 10% Ziziphus Spina is similar to Clotrimazole in eliminating C. Albicans.