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Drug administration to the central nervous system (CNS) has become a great obstacle because of several biological barriers, such as the blood-brain barrier, therefore, brain targeting insights are a light for scientists to move forward for treating neurogenerative diseases using advanced non-invasive methods. The current demand is to use a potential direct route as the nasal administration to transport drugs into the brain enhancing the BBB permeability and hence, increasing the bioavailability. Interestingly, recent techniques have been implanted in formulating nanocarriers-based therapeutics for targeting and treating ischemic stroke using lipid or polymeric-based materials. Nanoparticulate delivery systems are set as an effective platform for brain targeting as polymeric nanoparticles and polymeric micelles or nanocarriers based on lipids for preventing drug efflux to promote optimal therapeutic medication concentration in the brain-diseased site. In recent years, there has been a notable increase in research publications and ongoing investigations on the utilization of drug-loading nanocarriers for the treatment of diverse CNS diseases. This review comprehensively depicts these dangerous neurological disorders, drug targeting challenges to CNS, and potential contributions as novel intranasal nano-formulations are being used to treat and regulate a variety of neurological diseases.

This study aims to explore the protective machinery of pegylated polymeric micelles of boswellic acid-selenium (PMBS) against secondary neuronal damage triggered by mild repetitive traumatic brain injury (RTBI). After PMBS characterization in terms of particle size, size distribution, zeta potential, and transmission electronic microscopy, the selected formula was used to investigate its potency against experimental RTBI. Five groups of rats were used; group 1 (control) and the other four groups were subjected to RTBI. Groups 2 was RTBI positive control, while 3, 4, and 5 received boswellic acid (BSA), selenium (SEL), and PMBS, respectively. The open-field behavioral test was used for behavioral assessment. Subsequently, brain tissues were utilized for hematoxylin and eosin staining, Nissl staining, Western blotting, and ELISA in addition to evaluating microRNA expression (miR-155 and miR-146a). The behavioral changes, oxidative stress, and neuroinflammation triggered by RTBI were all improved by PMBS. Moreover, PMBS mitigated excessive glutamate-induced excitotoxicity and the dysregulation in miR-155 and miR-146a expression. Besides, connexin43 (Cx43) expression as well as klotho and brain-derived neurotrophic factor (BDNF) were upregulated with diminished neuronal cell death and apoptosis because of reduced Forkhead Box class O3a(Foxo3a) expression in the PMBS-treated group. The current study has provided evidence of the benefits produced by incorporating BSA and SEL in PEGylated polymeric micelles formula. PMBS is a promising therapy for RTBI. Its beneficial effects are attributed to the manipulation of many pathways, including the regulation of miR-155 and miR-146a expression, as well as the BDNF /Klotho/Foxo3a signaling pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bottle gourd (BG) oil (family Cucurbitaceae) has several pharmacological activities including a reduction of the hazard of cardiovascular and atherosclerosis conditions. This work aimed to develop and optimize self-dispersing lipid formulations (SDLFs) of BG oil by applying a full 3 2 factorial design. The formulation variables (oil concentration and surfactant mixture ratio) showed an obvious impact on the characters of the prepared BG-SDLFs including droplet size (DS), polydispersity index (PDI), emulsification time (ET), and transmission percentage (Tr%). The optimum BG-SDLF composed of 30% oil and Tween 80/Cremophor ® RH40 (1:1) showed good emulsification characteristics and a better drug release profile compared with BG oil. In vivo study in isoproterenol-injected rats showed that BG oil and the optimized BG-SDLF improved cardiac function, by elevating the miRNA-23a gene expression level and decreasing miRNA-21 gene expression. They also caused the inhibition of the plasma B-type natriuretic peptide (BNP), N-terminal proatrial natriuretic peptide (NT-pro-BNP), cystatin c, galectin-3, lipoprotein-associated phospholipase A2 (Lp-PLA2), matrix metallopeptidase 2 (MMP2), cardiac troponin I (cTnI), and cardiac troponin T (cTnT). Our study demonstrated that BG oil and the optimized BG-SDLF provided a cardioprotection against isoproterenol-induced cardiac toxicity with better results in groups treated with the optimized BG-SDLF.

The present study aimed to develop fast melting tablets (FMTs) using silymarin (SM) owing to FMTs rapid disintegration and dissolution. FMTs represent a pathway to help patients to increase their compliance level of treatment via facile administration without water or chewing beside reduction cost. One of the methods for FMTs formulation is lyophilization. Optimization of SM-FMTs was developed via a 3 2 factorial design. All prepared SM-FMTs were evaluated for weight variation, thickness, breaking force, friability, content uniformity, disintegration time (DT), and % SM released. The optimized FMT formula was selected based on the criteria of scoring the fastest DT and highest % SM released after 10 min (Q 10 ). Optimized FMT was subjected to Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM) besides investigating its lung-protective efficacy. All SM-FMT tablets showed acceptable properties within the pharmacopeial standards. Optimized FMT (F7) scored a DT of 12.5 ± 0.64 Sec and % SM released at Q 10 of 82.69 ± 2.88%. No incompatibilities were found between SM and excipients, it showed a porous structure under SEM. The optimized formula decreased cytokines, up-regulated miRNA133a, and down-regulated miRNA-155 and COX-2 involved in the protection against lung toxicity prompted by HgCl 2 in a manner comparable to free SM at the same dosage.

Oleogel consists of hydrophobic solvent and an oleogelator. In this study, attempts were made to study the influence of Celecoxib solubility, concentration and dispersability on its release, absorption, and biological performance. Oleogels were prepared to study the formulation variables on its stability and release. Castor oil was selected as the oil and the oleogelator concentration was 4.5% w/w. F3 revealed the highest release and stability compared to other formulae. The percent permeated across the rat intestine showed a 7.5-fold increase over free Celecoxib, and its lifetime was found to be greater than 18 months. The efficacy of free Celecoxib and oleogel formulae to treat rats with ulcerative colitis was done via the induction of ulcerative colitis (UC) through administration of 5% dextran sodium sulphate (DSS). Celecoxib besides its formulae significantly reduced the release of Leucine rich 2 glycoprotein (LRG), Myeloperoxidase (MPO), Tumor necrosis factor-α (TNF-α), proinflammatory cytokine expression, High mobility group box 1 (HMGB1), Nuclear factor kappa B (NF-ΚB), Trefoil Factor 3 (TFF3), Metalloproteinase-3 (MMP3), and miRNA31. Moreover, F3 significantly increased the colonic cAMP in DSS treated rats and reduced the intestinal inflammation beside healing of mucosa and restitution of the epithelium of the gastrointestinal tract.

The current study aimed to load terconazole (TCZ), an antifungal agent with low permeability characteristics, into highly deformable bilosomes (HBs) for augmenting its topical delivery. HBs contain edge activator in addition to the constituents of traditional bilosomes (Span 60, cholesterol, and bile salts). More elasticity is provided to the membrane of vesicles by the existence of edge activator and is expected to increase the topical permeation of TCZ. HBs were formulated using ethanol injection technique based on 2 4 complete factorial design to inspect the impact of various formulation variables (bile salt type and amount, edge activator type, and sonication time) on HBs characteristics (entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP)). The optimum formula (HB14) was decided based on Design-Expert ® software and was utilized for further explorations. HB14 exhibited EE% = 84.25 ± 0.49%, PS = 400.10 ± 1.69 nm, PDI = 0.23 ± 0.01, and ZP = - 56.20 ± 0.00 mV. HB14 showed spherical vesicles with higher deformability index (9.94 ± 1.91 g) compared to traditional bilosomal formula (3.49 ± 0.49 g). Furthermore, HB14 showed superior inhibition of Candida albicans growth relative to TCZ suspension using XTT (2,3-bis(2-methyloxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reduction assay. Moreover, in vivo skin deposition studies revealed superior TCZ deposition inside the skin from HB14 compared to traditional bilosomal formula and TCZ suspension. Moreover, histopathological examination in rats assured the safety of HB14 for topical use. Concisely, the obtained outcomes confirmed the pronounced efficacy of HBs for topical delivery of TCZ.

Various invasive and noninvasive methods have been used for measuring primary implant stability. Periotest damping device and resonance frequency analysis with the Osstell device have been classified as noninvasive methods. Primary and secondary implant stability measurements using both devices have given reproducible quantitative values. In this clinical randomized trial, a general correlation was evaluated between the implant stability recorded using both Osstell and Periotest devices on the day of implant installation and 3 months after healing for the submerged and nonsubmerged loading protocols. The present study also investigated whether the difference in gender of the included patients would have an effect on the correlation between the two devices. Eighty completely edentulous patients were recruited, and all patients ranged from 50 to 69 years of age. Overall, 56 men and 24 women were included, with a mean age of 62.5 years for men and 59.6 years for women. A single implant was installed in the midline of the completely edentulous mandible to improve retention of the patient's lower denture. After implant installation, one implant stability quotient (ISQ) value at the buccal surface was recorded, and then the Periotest M device was used to measure the damping effect (Periotest value [PTV]) of the installed implant using the smart peg screwed to the implant. Patients were then randomized into 2 groups using sealed envelopes: the submerged and nonsubmerged groups. For both groups, all ISQ and Periotest readings were recorded in the patient's case report file on the day of implant installation and 3 months after healing. When the ISQ of the buccal surface was correlated to the PTV, there was a moderate negative statistically significant correlation between the 2 readings (correlation coefficient = -.466, P = .000). There tended to be a weak negative correlation between the 2 devices in the male group (correlation coefficient = .395, P = .046) during implant installation, although there tended to be no correlation between the 2 devices in the female group (correlation coefficient = -.367, P = .342). After 3 months of healing, when correlating the readings of the buccal surface of the Osstell with that of the Periotest within each group (submerged and nonsubmerged), there was no statistically significant correlation between the readings within each group (correlation coefficient = -.014, -.430, P = .942, P = .052, respectively). However, there was a strong negative statistically significant correlation between the 2 devices for the female group for both the nonsubmerged group (correlation coefficient = -.823, P = .003) and submerged group (correlation coefficient = -.857, P = .014), whereas there was no statistically significant correlation within the male group for both the nonsubmerged group (correlation coefficient = -.377, P = .123) and submerged group (correlation coefficient = -.022, P = .940). The correlation between the Osstel and Periotest device remains controversial. The present study concluded that there is a significant negative correlation between the 2 devices when recording primary implant stability, although this significance is lost after 3 months of loading when recording secondary implant stability. Gender also affects the implant stability recording, which is mainly due to the difference in bone density between men and women.

Ethylmorphine hydrochloride (EtM) is a derivative of morphine used as analgesic to treat severe pain in case of cancer and bone injury. This study aimed to formulate and evaluate core in cup tablets containing 2 doses of EtM, the cup was formulated as lyophilized oro-dispersible tablet (ODT) for immediate release (IR), and the core was formulated as directly compressed tablet for sustained release (SR). Factorial design was adopted for the optimization of tablets prepared via lyophilized form and direct compression techniques: a 4 1 .2 2 design was used for the former, while a 3 2 one was used for the latter. All prepared tablets showed acceptable physical properties which were in accordance with pharmacopeial standards. Two lyophilized ODTs (F9 and F10) formulae were selected as the cup for instant release. While one directly compressed tablet formula (S6) was selected based on the in vitro release profile to represent the sustained core, the outcome was 2 core in cup tablets, namely B1 and B2 which were evaluated for their in vivo absorption and showed a maximum plasma concentration (Cp max ) of 354.12 ± 17.55 ng/mL and 350.82 ± 12.15 ng/mL respectively attained after 3.0 h which were twofolds significantly higher in comparison to the market tablet with Cp max of only 172.05 ± 12.53 ng/mL attained after 2.20 ± 0.24 h.

Myocardial infarction (MI) is the principal cause of death in many countries. Silymarin (SM) is a herbal antioxidant and can be efficiently used in preventing cardiovascular diseases (CVDs). The study is aimed to enhance the absorption rate and biological activity of SM by using liquisolids besides investigating the cardioprotective activity of SM and its selected liquisolid formula against isoproterenol prompted cardiotoxicity in rats. Eight formulae were prepared according to (2 3 ) full-factorial design. The effect of viscosity increasing agent type and concentration, as well as the carrier/coat ratio on the dissolution rate and angle of repose were studied. All formulae were tested for content uniformity, micromeritic properties, dissolution performance besides the evaluation of its physicochemical properties, and scanning electron microscopy (SEM). Based on the factorial design outcomes, the highest desirability was obtained from F3 with excipient ratio value (R) of 20%, dissolution rate at Q 5 min of 26.9%, and angle of repose of 19. Oral administration of F3 liquisolid and SM revealed a significant protective efficacy against the modification of cardiac plasma markers, brain natriuretic peptide (BNP), interleukin-10 (IL-10), vascular endothelial growth factor (VEGF), and transforming growth factor (TGF)-β1 besides cardiac superoxide dismutase (SOD), malondialdehyde (MDA), and total protein kinase-1 (Akt-1) levels. Additionally, they minimized cardiac inducible nitric oxide synthase (iNOS), microRNA-34a (miR-34a), and p38 mitogen-activated protein kinase (p38-MAPK) levels. In conclusion, F3 liquisolid compact possessed an overall pronounced results over pure SM reckoned to its enhanced solubility and efficacy.

The present study demonstrates a preparative medium-pressure liquid chromatography (MPLC) method for isolation of Morin besides evaluating its efficacy in comparison with its self-nanoemulsifying drug delivery (SNEDD) and nanoemulsion (NE) systems against in-vivo HgCl 2 -induced lung toxicity in rats. Morin was isolated from hydroalcoholic (70%) extract of Psidium guajava leaves by MPLC. The purity (> 90%) was done using HPLC. Screening of Morin solubility was studied to identify the components of each system. The prepared formulae were assessed for their thermodynamic stability, rheological properties, emulsification time, size, zeta potential beside its dissolution. The selected formulae according to the smallest size, highest zeta potential, and release at Q 10 min were assessed for their morphology by transmission electron microscopy (TEM) and protective potential against in-vivo HgCl 2 -induced lung toxicity in rats. All formulae were stable with Newtonian flow, emulsification time was (< 134 ± 10 s), size (< 40 nm) with zeta potential (> - 10.36 ± 0.99 mV). The extent of free Morin dissolved from capsule showed significantly the lowest percent released (22.21 ± 1.45%) while in case of SNEDDs and NEs (> 55% dissolved). The morphology of the selected Morin formulae showed spherical shape within the nano-range. Supplementation of Morin and its formulae to rats caused significant decrease in C-reactive protein, hepatoglobin, hydroproxide, lung nitric oxide, tumor necrosis factor-α, immunoglobulin (E and G), histamine, malondialdehyde, and interleukin-6 gene expression while significant increase in immunoglobulin A, caspase-3, catalase, and glutathione peroxidase compared to HgCl 2 . SNEDD and NE formulae could ameliorate lung toxicity in a mechanism related to their antioxidant and anti-inflammatory potential.