Evaluation of Brain Targeting and Antipsychotic Activity of Nasally Administrated Ziprasidone Lipid-Polymer Hybrid Nanocarriers.

The feasibility of using lipid-polymer hybrid (LPH) nanocarriers as a potential platform for the intranasal delivery of ziprasidone (ZP), a second-generation antipsychotic, was explored. Different ZP-loaded LPH composed of a PLGA core and cholesterol-lecithin lipid coat were prepared using a single step nano-precipitation self-assembly technique. Modulation of polymer, lipid and drug amounts, as well as stirring-speed-optimized LPH with a particle size of 97.56 ± 4.55 nm and a ZP entrapment efficiency (EE%) of 97.98 ± 1.22%. The brain deposition and pharmacokinetics studies proved the efficiency of LPH to traverse the blood-brain barrier (BBB) following intranasal delivery with a 3.9-fold increase in targeting efficiency compared to the intravenous (IV) ZP solution with a direct nose-to-brain transport percentage (DTP) of 74.68%. The ZP-LPH showed enhanced antipsychotic activity in terms of animals' hypermobility over an IV drug solution in schizophrenic rats. The obtained results showed that the fabricated LPH was able to improve ZP brain uptake and proved its antipsychotic efficiency.

Quetiapine Albumin Nanoparticles as an Efficacious Platform for Brain Deposition and Potentially Improved Antipsychotic Activity.

Quetiapine (QP) is a second-generation short-acting antipsychotic drug extensively metabolized in the liver, producing pharmacologically inactive metabolites and leading to diminished bioavailability. Therefore, this study aimed to develop an intravenous QP albumin nanoparticles (NPs) system for improving QP antipsychotic activity and brain targeting. QP-loaded albumin NPs were prepared by the desolvation method. The fabricated NPs were characterized in terms of particle size, zeta potential, entrapment efficiency (EE%), and in vitro drug release. In vivo pharmacokinetics and biodistribution in rats were studied. In addition, the antipsychotic activity of the optimized platform was also investigated. Human serum albumin (HSA) concentration, pH, and stirring time were modulated to optimize QP albumin NPs with a particle size of 103.54 ± 2.36 nm and a QP EE% of 96.32 ± 3.98%. In addition, the intravenous administration of QP albumin NPs facilitated QP brain targeting with a 4.9-fold increase in targeting efficiency compared to the oral QP solution. The QP albumin NPs improved the QP antipsychotic activity, indicated by suppressing rats' hypermobility and reducing the QP's extrapyramidal side effects. The obtained results proposed that intravenous QP- NPs could improve QP brain targeting and its antipsychotic efficiency.

Retama monosperma chemical profile, green synthesis of silver nanoparticles, and antimicrobial potential: a study supported by network pharmacology and molecular docking.

In this study, Retama monosperma extract (RME) was used for the green synthesis of silver nanoparticles (RME-AgNPs). RME's phenolic profile was identified by liquid chromatography coupled to mass spectroscopy (LC-ESI/MS/MS) technique. A tentative identification of 21 phenolic metabolites from the extract was performed. The produced RME-AgNPs showed UV absorbance at 443 nm. FTIR spectroscopy confirmed the presence of RME functional groups. In addition, XRD analysis confirmed the crystallography of RME-AgNPs via exhibiting peaks with 2θ values at 38.34°, 44.29°, and 64.65°. RME-AgNPs were spherical with particle sizes ranging from 9.87 to 21.16 nm, as determined by SEM and HR-TEM techniques. The zeta potential determined the particle's charge value as -15.25 mv. RME-AgNPs exhibited significantly higher antibacterial activity against Gram-negative (Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens, and Klebsiella pneumoniae) and Gram-positive bacteria (Bacillus subtilis and Staphylococcus aureus) compared to RME. Moreover, the SEM images of green-synthesized nanoparticles revealed severe damage and deformation in the bacterial cell wall of the different strains subjected to the current investigation. The bioinformatics study identified 266 targets, among which only 41 targets were associated with bacterial infections. The PI3K-Akt and Relaxin signaling pathways were the top KEGG signaling pathways. Molecular docking was also performed for the 21 identified compounds at the TNF-α active site; kaempferol-3-O-robinoside-7-O-rhamnoside had a higher binding energy (-6.8084). The findings of this study warrant the use of green-synthesized AgNPs from Retama monosperma as potential antibacterial agents.

Novel nasal niosomes loaded with lacosamide and coated with chitosan: A possible pathway to target the brain to control partial-onset seizures.

This work aimed to develop and produce lacosamide-loaded niosomes coated with chitosan (LCA-CTS-NSM) using a thin-film hydration method and the Box-Behnken design. The effect of three independent factors (Span 60 amount, chitosan concentration, and cholesterol amount) on vesicle size, entrapment efficiency, zeta potential, and cumulative release (8 h) was studied. The optimal formulation of LCA-CTS-NSM was chosen from the design space and assessed for morphology, in vitro release, nasal diffusion, stability, tolerability, and in vivo biodistribution for brain targeting after intranasal delivery. The vesicle size, entrapment, surface charge, and in vitro release of the optimal formula were found to be 194.3 nm, 58.3%, +35.6 mV, and 81.3%, respectively. Besides, it exhibits sustained release behavior, enhanced nasal diffusion, and improved physical stability. Histopathological testing revealed no evidence of toxicity or structural damage to the nasal mucosa. It demonstrated significantly more brain distribution than the drug solution. Overall, the data is encouraging since it points to the potential for non-invasive intranasal administration of LCA as an alternative to oral or parenteral routes.

Aceclofenac-Loaded Microspheres Prepared by Vesicular Ionotropic Gelation to Minimize Drug-induced Gastric Ulcers in Rats.

BACKGROUND: Aceclofenac is a non-steroidal anti-inflammatory drug and a potent analgesic. However, its oral ingestion may cause gastrointestinal problems, including dyspepsia, abnormal pain, nausea, diarrhea, and ulcerative colitis. OBJECTIVE: This study aimed to prepare vesicular-based enteric microspheres containing aceclofenac by ionotropic gelation technique to minimize gastric irritation in rats. METHODS: The micron-size vesicles were prepared by the ionic-orifice gelation method. Three types of vesicularbased microcapsules containing aceclofenac were prepared by employing sodium alginate as the coating material in combination with Eudragit L100, Eudragit S100, and polyvinylpyrrolidone PVP K90. The drug to sodium alginate to polymer ratios were 1:0.5:0.5, 1:1:1, and 1:1.5:1.5, respectively. Gelation of sodium alginate was induced by the dropwise addition of calcium chloride solution (10 % w/v). Aceclofenac-loaded microspheres were evaluated in terms of aceclofenac content and in vitro drug release, and FTIR, DSC, and XRD were used for physicochemical evaluation of some selected formulae. The effects of microencapsulation on aceclofenac-induced ulcerative activity in male Wistar rats were also investigated. RESULTS: The results indicated no interaction between aceclofenac and microcapsules forming polymers. In addition, microcapsules formulations M1, M4, and M7 gave maximal protection in acidic pH and optimal release in alkaline pH. The histopathological studies revealed that the reduction of ulceration is evident from the macroscopic and microscopic studies, which showed complete protection of the tissue morphology with no ulcers, indicating the effectiveness of the microcapsules system against aceclofenac-induced gastric ulceration in rats again. CONCLUSION: Ionotropic gelation seems to be a simple, efficient technique to prepare aceclofenac-loaded microspheres with a reduced risk of gastric ulceration. It is possible to overcome the problem of gastric damage while utilizing aceclofenac by avoiding the exposure of the drug to the ulcer-prone area of the gastrointestinal tract.

Fabrication and In Vitro/In Vivo Appraisal of Metronidazole Intra-Gastric Buoyant Sustained-Release Tablets in Healthy Volunteers.

Helicobacter pylori is thought to be the most common cause of peptic and duodenal ulcers. Eradication of this organism is now considered one of the lines of treatment of gastric and duodenal ulcers. This can be achieved via local delivery of antibacterial agents in high concentrations. Accordingly, our objective was to fabricate and evaluate sustained release floating tablets for metronidazole to extend the gastric residence period and control the release rate of metronidazole. Floating tablets containing cellulose derivatives and Avicel were prepared using direct compression. The rate of metronidazole release from the floating tablets (K = 6.278 mg min-1/2) was significantly lower than that from conventional tablets (K = 10.666 mg min-1/2), indicating sustained drug release, according to the Higuchi model, for more than 6 h in an acidic medium of 0.1 N HCl. In vivo study in healthy volunteers revealed significantly improved bioavailability; increased Tmax, AUC, and MRT; and significantly lower absorption rate constant after a single oral dose of 150 mg metronidazole as floating tablets. In addition, the significant increase in MRT indicated an in vivo sustained drug release. The floating tablets provided several benefits, including ease of preparation, absence of effervescent ingredients, and reliance on a pH-independent gel-forming agent to deliver metronidazole in a sustained manner. In conclusion, the prepared tablets could be promising for enhancing both local and systemic metronidazole efficacy.

Berberine Encapsulated Lecithin-Chitosan Nanoparticles as Innovative Wound Healing Agent in Type II Diabetes.

The aim of this research is to formulate a lecithin-chitosan based nanoparticulate system loaded with berberine (BER-LC-CTS-NPs) that could be integrated into a topically applied formulation and assessed for healing wounds in a diabetic animal model. In order to formulate BER-LC-CTS-NPs, soybean lecithin, isopropyl myristate, and berberine dispersed in ethanolic solution were added into an aqueous solution of chitosan dropwise with sonication. We assessed the influence of lecithin amount, chitosan amount, and isopropyl myristate concentration on particle diameter, zeta potential, and entrapment and employed a Box-Behnken statistical design. The resulting optimized BER-LC-CTS-NPs had a mean size of 168.4 nm, a surface charge of 33.1 mV, and entrapment of 82.3%. The optimized BER-LC-CTS-NPs showed a sustained in vitro release profile. Furthermore, the potential of the optimized BER-LC-CTS-NPs integrated into a topical gel formulation for wound healing in streptozocin-induced diabetic rats was assessed. Our findings show that combining chitosan and berberine in the nanoparticles produces a synergistic effect when it comes to wound healing. The optimized nanoparticulate system works by reducing inflammation, inducing blood vessels and fibroblast proliferation, and promoting mature collagen fibers deposition. Based on the experimental results, lecithin-chitosan nanoparticles loaded with berberine have evolved as a promising strategy for accelerating wound the healing process in diabetic patients. However, the clinical merits of the developed system need to be investigated in diabetic patients.

COVID-19: Vaccine Delivery System, Drug Repurposing and Application of Molecular Modeling Approach.

The acute respiratory syndrome coronavirus (SARS-CoV-2) has spread across the world, resulting in a pandemic COVID-19 which is a human zoonotic disease that is caused by a novel coronavirus (CoV) strain thought to have originated in wild or captive bats in the initial COVID outbreak region. The global COVID-19 outbreak started in Guangdong Province, China's southernmost province. The global response to the COVID-19 pandemic has been hampered by the sheer number of infected people, many of whom need intensive care before succumbing to the disease. The epidemic is being handled by a combination of disease control by public health interventions and compassionate treatment for those who have been impacted. There is no clear anti-COVID-19 medication available at this time. However, the need to find medications that can turn the tide has led to the development of a number of investigational drugs as potential candidates for improving outcomes, especially in the severely and critically ill. Although many of these adjunctive medications are still being studied in clinical trials, professional organizations have attempted to define the circumstances in which their use is deemed off-label or compassionate. It is important to remind readers that new information about COVID-19's clinical features, treatment options, and outcomes is released on a regular basis. The mainstay of treatment remains optimized supportive care, and the therapeutic effectiveness of the subsequent agents is still being studied.

Bucco-Adhesive Film as a Pediatric Proper Dosage Form for Systemic Delivery of Propranolol Hydrochloride: In-vitro and in-vivo Evaluation.

OBJECTIVE: To formulate and assess bucco-adhesive films of propranolol hydrochloride for pediatric use. METHODS: Different films were formulated adopting mucin, polyvinyl alcohol, chitosan and carbopol. A drug/polymer compatibility study was conducted adopting differential scanning calorimetry and Fourier transform infrared spectroscopy. The prepared films were physically investigated for variation of weight, propranolol content, thickness, surface pH, proportion of moisture, folding endurance and mucoadhesion. In vitro drug release study and kinetic analysis of the corresponding data have been conducted. The optimized formulation was selected for a bioavailability study using albino rabbits and adopting a developed HPLC method. The pharmacokinetic parameters of the drug were calculated following administration of the optimized film and the corresponding marketed oral tablets to albino rabbits. KEY FINDING: The compatibility study revealed the absence of drug/polymer interaction. The film formulations had suitable mucoadhesive and mechanical properties. The optimized formulation exhibited reasonable drug release that followed Higuchi diffusion pattern. The calculated AUC0-8h presented an enhancement in the bioavailability of propranolol hydrochloride from the selected film formulation by 1.9 times relative to the marketed propranolol oral tablets. CONCLUSION: These findings support that propranolol hydrochloride bucco-adhesive film can be considered as a proper effective dosage form for pediatric delivery.