Pectin nanoparticles loaded with nitric oxide donor drug: A potential approach for tissue regeneration.

The process of wound healing and tissue regeneration involves several key mechanisms to ensure the production of new tissues with similar cellular functions. This study investigates the impact of pectin, a natural polysaccharide, and nebivolol hydrochloride (NBV), a nitric oxide (NO) donor drug, on wound healing. Utilizing ionotropic gelation, NBV-loaded pectin nanoparticles were developed following a 2231 full factorial design. The optimized formulation, determined using Design expert® software, exhibited an encapsulation efficiency percentage of 70.68%, zeta potential of -51.4 mV, and a particle size of 572 nm, characterized by a spherical, discrete morphology. An in vivo study was conducted to evaluate the effectiveness of the optimal formulation in wound healing compared to various controls. The results demonstrated the enhanced ability of the optimal formulation to accelerate wound healing. Moreover, histopathological examination further confirmed the formulation's benefits in tissue proliferation and collagen deposition at the wound site 15 days post-injury. This suggests that the developed formulation not only promotes faster healing but does so with minimal side effects, positioning it as a promising agent for effective wound healing and tissue regeneration.

Synergistic therapeutic strategies and engineered nanoparticles for anti-vascular endothelial growth factor therapy in cancer.

Angiogenesis is one of the defining characteristics of cancer. Vascular endothelial growth factor (VEGF) is crucial for the development of angiogenesis. A growing interest in cancer therapy is being caused by the widespread use of antiangiogenic drugs in treating several types of human cancer. However, this therapeutic approach can worsen resistance, invasion, and overall survival. As we proceed, refining combination strategies and addressing the constraint of targeted treatments are paramount. Therefore, major challenges in using novel combinations of antiangiogenic agents with cytotoxic treatments are currently focused on illustrating the potential of synergistic therapeutic strategies, alongside advancements in nanomedicine and gene therapy, present opportunities for more precise interference with angiogenesis pathways and tumor environments. Nanoparticles have the potential to regulate several crucial activities and improve several drug limitations such as lack of selectivity, non-targeted cytotoxicity, insufficient drug delivery at tumor sites, and multi-drug resistance based on their unique features. The goal of this updated review is to illustrate the enormous potential of novel synergistic therapeutic strategies and the targeted nanoparticles as an alternate strategy for t treating a variety of tumors employing antiangiogenic therapy.

Intranasal Radioiodinated Ferulic Acid Polymeric Micelles as the First Nuclear Medicine Imaging Probe for ETRA Brain Receptor.

INTRODUCTION: The aim of this work was to prepare a selective nuclear medicine imaging probe for the Endothelin 1 receptor A in the brain. MATERIAL AND METHODS: Ferulic acid (an ETRA antagonist) was radiolabeled using 131I by direct electrophilic substitution method. The radiolabeled ferulic acid was formulated as polymeric micelles to allow intranasal brain delivery. Biodistribution was studied in Swiss albino mice by comparing brain uptake of 131I-ferulic acid after IN administration of 131I-ferulic acid polymeric micelles, IN administration of 131I-ferulic acid solution and IV administration of 131I-ferulic acid solution. RESULTS: Successful radiolabeling was achieved with an RCY of 98 % using 200 µg of ferulic acid and 60 µg of CAT as oxidizing agents at pH 6, room temperature and 30 min reaction time. 131I-ferulic acid polymeric micelles were successfully formulated with the particle size of 21.63 nm and polydispersity index of 0.168. Radioactivity uptake in the brain and brain/blood uptake ratio for I.N 131I-ferulic acid polymeric micelles were greater than the two other routes at all periods. CONCLUSION: Our results provide 131I-ferulic acid polymeric micelles as a hopeful nuclear medicine tracer for ETRA brain receptor.

Injectable systems of chitosan in situ forming composite gel incorporating linezolid-loaded biodegradable nanoparticles for long-term treatment of bone infections.

The objective of the current study was to create an efficient, minimally invasive combined system comprising in situ forming hydrogel loaded with both spray-dried polymeric nanoparticles encapsulating linezolid and nanohydroxyapatite for local injection to bones or their close vicinity. The developed system was designed for a dual function namely releasing the drug in a sustained manner for long-term treatment of bone infections and supporting bone proliferation and new tissues generation. To achieve these objectives, two release sustainment systems for linezolid were optimized namely a composite in situ forming chitosan hydrogel and spray-dried PLGA/PLA solid nanoparticles. The composite, in situ forming hydrogel of chitosan was prepared using two different gelling agents namely glycerophosphate (GP) and sodium bicarbonate (NaHCO3) at 3 different concentrations each. The spray-dried linezolid-loaded PLGA/PLA nanoparticles were developed using a water-soluble carrier (PVP K30) and a lipid soluble one (cetyl alcohol) along with 3 types of DL-lactide and/or DL-lactide-co-glycolide copolymer using nano-spray-drying technique. Finally, the optimized spray-dried linezolid nanoparticles were incorporated into the optimized composite hydrogel containing nanohydroxy apatite (nHA). The combined hydrogel/nanoparticle systems displayed reasonable injectability with excellent gelation time at 37 °C. The optimum formulae sustained the release of linezolid for 7-10 days, which reveals its ability to reduce the frequency of injection during the course of treatment of bones infections and increase the patients' compliance. They succeeded to alleviate the bone infections and the associated clinical, biochemical, radiological, and histopathological changes within 2-4 weeks of injection. As to the state of art in this study and to the best of our knowledge, no such complete and systematic study on this type of combined in situ forming hydrogel loaded with spray-dried nanoparticles of linezolid is available yet in literatures.

Magnetic targeting of lornoxicam/SPION bilosomes loaded in a thermosensitive in situ hydrogel system for the management of osteoarthritis: Optimization, in vitro, ex vivo, and in vivo studies in rat model via modulation of RANKL/OPG.

Osteoarthritis is a bone and joint condition characterized pathologically by articular cartilage degenerative damage and can develop into a devastating and permanently disabling disorder. This investigation aimed to formulate the anti-inflammatory drug lornoxicam (LOR) into bile salt-enriched vesicles loaded in an in situ forming hydrogel as a potential local treatment of osteoarthritis. This was achieved by formulating LOR-loaded bilosomes that are also loaded with superparamagnetic iron oxide nanoparticles (SPIONs) for intra-muscular (IM) administration to improve joint targeting and localization by applying an external magnet to the joint. A 31.22 full factorial design was employed to develop the bilosomal dispersions and the optimized formula including SPION (LSB) was loaded into a thermosensitive hydrogel. Moreover, in vivo evaluation revealed that the IM administration of LSB combined with the application of an external magnet to the joint reversed carrageen-induced suppression in motor activity and osteoprotegerin by significantly reducing the elevations in mitogen-activated protein kinases, extracellular signal-regulated kinase, and receptor activator of nuclear factor kappa beta/osteoprotegerin expressions. In addition, the histopathological evaluation of knee joint tissues showed a remarkable improvement in the injured joint tissues. The results proved that the developed LSB could be a promising IM drug delivery system for osteoarthritis management.

Improvement of adult female acne with a novel weekly estradiol loaded peel off mask. A split face, placebo controlled study.

BACKGROUND: Adult female acne is characterized by a relapsing eruption of acne in individuals who are 25 years or older. It usually shows slower response to the traditional adolescent acne treatments. Usually, androgens promote acne by stimulating sebum production, while estrogens have the opposite effect by reducing sebum output when present in adequate quantities. Estradiol is the female sex hormone with the highest absolute serum levels and the highest estrogenic activity during a woman's reproductive years. Peel-off facial masks were suggested to intensify the effect of the added active ingredient through forming an occlusive film after drying. OBJECTIVES: to study the safety and efficacy of weekly topical estradiol 0.05% in the treatment of adult acne in females. METHODS: Twenty female patients with adult acne were subjected to once weekly application of estradiol 0.05% and placebo masks to either side of the face for 8 weeks. Acne lesion count was performed at baseline, at each visit and 8 weeks after end of treatment. RESULTS: At the end of the treatment period, the treated side showed significant improvement of comedones, papules and pustules. Although, lesions count increased 2 months after stopping treatment, they were still significantly less on the estradiol side compared to placebo. No side effects were reported. LIMITATIONS: The limited number of patients studied and the limited follow-up period. The estradiol effect was not studied on cellular and molecular levels. CONCLUSIONS: Topical estradiol peel off mask can be a promising convenient, safe and effective treatment for adult acne in women.

Controlling the Evolution of Selective Vancomycin Resistance through Successful Ophthalmic Eye-Drop Preparation of Vancomycin-Loaded Nanoliposomes Using the Active-Loading Method.

Vancomycin is the front-line defense and drug of choice for the most serious and life-threatening methicillin-resistant Staphylococcus aureus (MRSA) infections. However, poor vancomycin therapeutic practice limits its use, and there is a consequent rise of the threat of vancomycin resistance by complete loss of its antibacterial activity. Nanovesicles as a drug-delivery platform, with their featured capabilities of targeted delivery and cell penetration, are a promising strategy to resolve the shortcomings of vancomycin therapy. However, vancomycin's physicochemical properties challenge its effective loading. In this study, we used the ammonium sulfate gradient method to enhance vancomycin loading into liposomes. Depending on the pH difference between the extraliposomal vancomycin-Tris buffer solution (pH 9) and the intraliposomal ammonium sulfate solution (pH 5-6), vancomycin was actively and successfully loaded into liposomes (up to 65% entrapment efficiency), while the liposomal size was maintained at 155 nm. Vancomycin-loaded nanoliposomes effectively enhanced the bactericidal effect of vancomycin; the minimum inhibitory concentration (MIC) value for MRSA decreased 4.6-fold. Furthermore, they effectively inhibited and killed heteroresistant vancomycin-intermediate S.aureous (h-VISA) with an MIC of 0.338 µg mL-1. Moreover, MRSA could not develop resistance against vancomycin that was loaded into and delivered by liposomes. Vancomycin-loaded nanoliposomes could be a feasible solution for enhancing vancomycin's therapeutic use and controlling the emerging vancomycin resistance.

Topical metformin 30% gel in the treatment of acne vulgaris in women, a split face, placebo-controlled study.

Acne vulgaris (AV), a widely common disorder, that negatively affects the quality of life. Metformin is a relatively safe, cheap and well tolerated drug that is widely used in the treatment of Diabetes. Systemic metformin has demonstrated promising results in treating acne, while topically it was studied for melasma and recalcitrant central centrifugal cicatricial alopecia. To study the safety and efficacy of topical metformin 30% in the treatment of AV. Twenty-seven female AV patients were asked to blindly apply metformin and placebo gels to either side of the face for 12 weeks. AV lesion count was performed at baseline, at each visit and 4 weeks after end of treatment. At the end of the treatment period, the treated side showed significant improvement of comedones, papules and nodules but not pustules. Although, lesions count increased 1 month after stopping treatment, comedones and papules numbers were still significantly less on the metformin side compared to placebo. No side effects were reported. The limited number of patients studied and the limited follow-up period. The metformin effect was not studied on cellular and molecular levels. Topical metformin nanoemulsion gel can be a promising safe and effective treatment of AV.

Green Synthesis of Highly Fluorescent Carbon Dots from Bovine Serum Albumin for Linezolid Drug Delivery as Potential Wound Healing Biomaterial: Bio-Synergistic Approach, Antibacterial Activity, and In Vitro and Ex Vivo Evaluation.

A simple and green approach was developed to produce novel highly fluorescent bovine serum albumin carbon dots (BCDs) via facile one-step hydrothermal treatment, using bovine serum albumin as a precursor carbon source. Inherent blue photoluminescence of the synthesized BCDs provided a maximum photostability of 90.5 ± 1.2% and was characterized via TEM, FT-IR, XPS, XRD, UV-visible, and zeta potential analyses. By virtue of their extremely small size, intrinsic optical and photoluminescence properties, superior photostability, and useful non-covalent interactions with the synthetic oxazolidinone antibiotic linezolid (LNZ), BCDs were investigated as fluorescent nano-biocarriers for LNZ drug delivery. The release profile of LNZ from the drug delivery system (LNZ-BCDs) revealed a distinct biphasic release, which is beneficial for mollifying the lethal incidents associated with wound infection. The effective wound healing performance of the developed LNZ-BCDs were evaluated through various in vitro and ex vivo assays such as MTT, ex vivo hemolysis, in vitro antibacterial activity, in vitro skin-related enzyme inhibition, and scratch wound healing assays. The examination of LNZ-BCDs as an efficient wound healing biomaterial illustrated excellent biocompatibility and low cytotoxicity against normal human skin fibroblast (HSF) cell line, indicating distinct antibacterial activity against the most common wound infectious pathogens including Staphylococcus aureus (ATCC® 25922) and methicillin-resistant Staphylococcus aureus, robust anti-elastase, anti-collagenase, and anti-tyrosinase activities, and enhanced cell proliferation and migration effect. The obtained results confirmed the feasibility of using the newly designed fluorescent LNZ-BCDs nano-bioconjugate as a unique antibacterial biomaterial for effective wound healing and tissue regeneration. Besides, the greenly synthesized BCDs could be considered as a great potential substitute for toxic nanoparticles in biomedical applications due to their biocompatibility and intense fluorescence characteristics and in pharmaceutical industries as promising drug delivery nano-biocarriers for effective wound healing applications.

Novel naringin tablet formulations of agro-resides based nano/micro crystalline cellulose with neuroprotective and Alzheimer ameliorative potentials.

This study aimed to prepare micro/nanocrystalline cellulose-loaded naringin (NAR) tablets and evaluate their neuro-protective/therapeutic potentials in Alzheimer's disease (AD) model. Micro/nanocellulose was prepared from different agro-wastes, and the different cellulose preparations were then used to formulate eight oral tablets of naringin micro/nanoparticles by direct compression. AD-like symptoms were induced in adult male Sprague Dawley rats by co-administration of 150 mg/kg AlCl3 and 300 mg/kg D-galactose (oral administration/one week), and NAR tablets were assessed for neuroprotective/therapeutic potentials in terms of behavioral changes, levels of neurodegenerative and inflammatory markers, brain redox status, neurotransmitter tones, and cortex/hippocampus histopathological alterations. NAR treatments have significantly reversed the neurotoxic effect of AlCl3 as demonstrated by improved spatial and cognitive memory functions and promoted antioxidant defense mechanisms in treated AD animals. Also, the neurodegeneration was markedly restrained as reflected by marked histopathological enhancement, and prevention/amelioration of neuropsychiatric disorders, besides the restorative effect on dysregulated neurotransmitters tone. Both NAR tablet forms showed an overall higher ameliorative effect compared to the DPZ reference drug. The formulated tablets represent promising neuroprotective/therapeutic agents for Alzheimer's disease.

Novel linezolid loaded bio-composite films as dressings for effective wound healing: experimental design, development, optimization, and antimicrobial activity.

Biphasic release bio-composite films of the low water-soluble drug, linezolid (LNZ), were formulated using the solvent casting technique. Different polymers and plasticizers (gelatin, Tween 80, polyethylene glycol 400, and glycerol) were assessed for the preparation of bio-composite films. An I-optimal design was applied for the optimization and to study the impact of polymer concentration (X1), plasticizer concentration (X2), polymer type (X3), and plasticizer type (X4) on different LNZ-loaded bio-composite films. The film thickness, moisture content, mechanical properties, swelling index, and percentage of drug release at fixed times opted as dependent variables. Results demonstrated a significant effect of all independent variables on the drug release from the prepared bio-composite films. The plasticizer concentration significantly increased the thickness, moisture content, elongation at break, swelling index, and in vitro drug release and significantly reduced the tensile strength. The optimized LNZ-loaded bio-composite film comprised of 15% Tween 80 and 30% PEG 400 was highly swellable, elastic, acceptable tensile properties, safe, maintained a moist environment, and indicated great antimicrobial activity against both Staphylococcus aureus (ATCC® 25922) and methicillin-resistant Staphylococcus aureus (MRSA), which are common wound infectious bacteria. The present study concludes that the optimized LNZ-loaded bio-composite film was successfully designed with fast drug release kinetics and it could be regarded as a promising novel antimicrobial wound dressing formulation.

Antibacterial and Anti-Inflammatory Activities of Thymus vulgaris Essential Oil Nanoemulsion on Acne Vulgaris.

Antibiotics are frequently used in acne treatment and their prolonged use has led to an emergence of resistance. This study aimed to investigate the use of natural antimicrobials as an alternative therapy. The antimicrobial and anti-inflammatory activities of five commonly used essential oils (EOs) (tea tree, clove, thyme, mentha and basil EOs), and their possible mechanisms of action against Cutibacterium acnes and Staphylococcus epidermidis, were explored. The effect of the most potent EO on membrane permeability was elucidated and its anti-inflammatory action, when formulated as nanoemulsion, was tested in an in vivo acne model. The in vitro studies showed that thyme EO had the most potent antimicrobial and antibiofilm activity, with phenolics and terpenoids as main antimicrobial constituents of EO. Thyme EO affected cell membrane permeability of both bacterial species, evident by the detection of the leakage of intracellular ions and membrane integrity by the leakage of nucleic acids. Morphological alteration in bacterial cells was confirmed by transmission electron microscopy. Thyme EO nanoemulsion led to the suppression of an inflammatory response in acne animal models along with a bacterial load decrease and positive histopathological changes. Collectively, thyme EO nanoemulsion showed potent antimicrobial and anti-inflammatory effects compared to the reference antibiotics, suggesting its effectiveness as a natural alternative in acne treatment.

A Nano-Liposomal Formulation of Caffeic Acid Phenethyl Ester Modulates Nrf2 and NF-κß Signaling and Alleviates Experimentally Induced Acute Pancreatitis in a Rat Model.

The currently available management strategies for acute pancreatitis are inadequately effective which calls for exploration of new approaches to treat this condition. Caffeic acid phenethyl ester (CAPE) is a major bioactive constituent of honeybee propolis with promising therapeutic and preventive applications. However, its pharmaceutical potential and clinical use are hindered by its poor water solubility and limited plasma stability. In this study, we aimed to prepare, characterize and evaluate a CAPE-loaded nanoliposomal formulation to improve the efficacy of CAPE for the management of acute pancreatitis. The CAPE-loaded nanoliposomes (CAPE-loaded-NL) were prepared by a thin layer evaporation technique and were optimized using three edge activators. CAPE-loaded-NL were characterized for their vesicle size (VS), zeta potential (ZP), encapsulation efficiency (EE), polydispersity index (PDI), crystalline state and morphology. The protective effect of the optimal CAPE-loaded-NL was evaluated in a rat model of acute pancreatitis induced by administering a single intraperitoneal injection of L-ornithine. Oral pretreatment with CAPE-loaded-NL significantly counteracted ornithine-induced elevation in serum activities of pancreatic digestive enzymes and pancreatic levels of malondialdehyde, nuclear factor kappa B (NF-κB) p65, tumor necrosis factor-alpha, nitrite/nitrate, cleaved caspase-3 and myeloperoxidase activity. Moreover, pretreatment with CAPE-loaded-NL significantly reinstated the ornithine-lowered glutathione reductase activity, glutathione, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 levels and ATP/ADP ratio, and potentiated the Bcl-2/Bax ratio in pancreatic tissue. CAPE-loaded-NL displayed superior antioxidant, anti-inflammatory and anti-apoptotic effects compared to free CAPE oral suspension and achieved a more potent correction of the derangements in serum amylase and pancreatic myeloperoxidase activities. The histological observations were in line with the biochemical findings. Our results suggest that CAPE-loaded-NL provide a promising interventional approach for acute pancreatitis mainly through the enhancement of the exerted antioxidant, anti-inflammatory and anti-apoptotic effects which may be mediated, at least in part, through modulation of Nrf2 and NF-κß signaling.

Eplerenone repurposing in management of chorioretinopathy: Mechanism, nanomedicine-based delivery applications and future trends.

Chronic central serous chorioretinopathy (CSCR) is an ocular threatening disease, a common cause of central vision loss, affecting the posterior pole of the eye. Eplerenone (EPL) is a selective mineralocorticoid receptor antagonist that is primarily used to treat hypertension. Recently, it has shown many benefits in modifying the physio-pathological processes occurring upon stimulation of renin-angiotensin-aldosterone system at the ocular level. In CSCR treatment, several clinical studies and case reports prove the efficacy and safety of EPL. However, setbacks for such studies include a relatively small number of participants and short follow-up periods. This review article is intended to describe theories about the nature and classification of CSCR and recapitulate EPL therapeutic benefits as selective mineralocorticoid receptor antagonist in the treatment of CSCR. Furthermore, we survey the literature on clinical studies discussing the results of use of EPL in treatment of CSCR. In addition, EPL therapeutic formulations that have been developed are described, and future potential delivery systems will be suggested.

Evaluation of the effect of topical tacrolimus 0.03% versus cyclosporine 0.05% in the treatment of dry eye secondary to Sjogren syndrome.

PURPOSE: To compare the effect of topical application of tacrolimus 0.03% eyedrops versus cyclosporine 0.05% in Sjogren syndrome subjects with severe dry eyes. DESIGN: A prospective single-blinded simply randomized controlled study. METHODOLOGY: 60 Sjogren patients were randomized intoGroup A: 30 patients were instructed to put tacrolimus 0.03% eyedrops in one eye for 6 months and placebo eyedrops in the other eye, (N = 30, 44.9 ± 12.58 years).Group B: 30 patients were instructed to put cyclosporine 0.05% eyedrops in one eye for 6 months and placebo eyedrops in the other eye (N = 30, 49.4 ± 12.92 years).Main outcome measures: Patients were evaluated at day 0, 90, and 180 for Ocular Surface Disease Index Questionnaire (OSDI), frequency of use of artificial tears, average fluorescein tear break up time (TBUT), ocular surface staining scores, Schirmer I test, meibum quality, and expressibility scores. RESULTS: Upon comparing both eyedrops, the mean value of OSDI decrease was 38.25 ± 18.29% versus 31.69 ± 18.57% (p-value 0.09), SICCA score decrease was 2.97 ± 1.92 versus 2.27 ± 2.02 (p-value 0.124) the decrease in artificial tear substitute use was 3.90 ± 2.22 versus 3.63 ± 1.92 (p-value 0.616), increase in Schirmer I values were 4.10 ± 4.21 and 4.26 ± 2.00 (p-value 0.590) in eyes treated with tacrolimus and cyclosporine respectively. Neither of them affected meibum quality or expressibility scores. CONCLUSION: Both tacrolimus and cyclosporine significantly improved patient symptoms, frequency of artificial tears use and ocular surface staining compared to placebo-controlled eyes. However, no significant difference regarding the efficacy of both eyedrops at the end of 6 months treatment of severe dry eyes of Sjögren syndrome patients. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier: NCT03865888.

Triblock Copolymer Bioinks in Hydrogel Three-Dimensional Printing for Regenerative Medicine: A Focus on Pluronic F127.

Three-dimensional (3D) bioprinting is a novel technique applied to manufacture semisolid or solid objects via deposition of successive thin layers. The widespread implementation of the 3D bioprinting technology encouraged scientists to evaluate its feasibility for applications in human regenerative medicine. 3D bioprinting gained much interest as a new strategy to prepare implantable 3D tissues or organs, tissue and organ evaluation models to test drugs, and cell/material interaction systems. The present work summarizes recent and relevant progress based on the use of hydrogels for the technology of 3D bioprinting and their emerging biomedical applications. An overview of different 3D printing techniques in addition to the nature and properties of bioinks used will be described with a focus on hydrogels as suitable bioinks for 3D printing. A comprehensive overview of triblock copolymers with emphasis on Pluronic F127 (PF127) as a bioink in 3D printing for regenerative medicine will be provided. Several biomedical applications of PF127 in tissue engineering, particularly in bone and cartilage regeneration and in vascular reconstruction, will be also discussed. Impact statement The current review highlights the use of three-dimensional (3D) bioprinting for regenerative medicine, stressing the manipulation of hydrogels as the most commonly used bioinks. The advantages and shortcomings of using hydrogels for 3D printing procedures are discussed with a particular focus on triblock copolymers and Pluronics. A brief overview of applying bioink Pluronic F127 in applications of 3D bioprinting for tissue reconstruction is also provided.

Itraconazole-Loaded Ufasomes: Evaluation, Characterization, and Anti-Fungal Activity against Candida albicans.

Numerous obstacles challenge the treatment of fungal infections, including the uprising resistance and the low penetration of available drugs. One of the main active agents against fungal infections is itraconazole (ITZ), with activity against a broad spectrum of fungi while having few side effects. The aim of this study was to design ufasomes, oleic acid-based colloidal carriers, that could encapsulate ITZ to improve its penetration power. Employing a 2231 factorial design, the effect of three independent factors (oleic acid amount, cholesterol concentration, and ITZ amount) was investigated and evaluated for the percentage encapsulation efficiency (%EE), particle size (PS), and zeta potential (ZP). Optimization was performed using Design® expert software and the optimized ITZ-loaded ufasomes obtained had %EE of 99.4 ± 0.7%, PS of 190 ± 1 nm, and ZP of -81.6 ± 0.4 mV, with spherical unilamellar morphology and no aggregation. An in vitro microbiological study was conducted to identify the minimum inhibitory concentration of the selected formula against Candida albicans, which was found to be 0.0625 µg/mL. Moreover, the optimized formula reduced the expression of toll-like receptors-4 and pro-inflammatory cytokine IL-1ß secretion in the C. albicans-infected fibroblasts, indicating that the proposed ITZ-loaded ufasomes are a promising drug delivery system for ITZ.

Recent advances in the local antibiotics delivery systems for management of osteomyelitis.

Chronic osteomyelitis is a challenging disease due to its serious rates of mortality and morbidity while the currently available treatment strategies are suboptimal. In contrast to the adopted systemic treatment approaches after surgical debridement in chronic osteomyelitis, local drug delivery systems are receiving great attention in the recent decades. Local drug delivery systems using special carriers have the pros of enhancing the feasibility of penetration of antimicrobial agents to bone tissues, providing sustained release and localized concentrations of the antimicrobial agents in the infected area while avoiding the systemic side effects and toxicity. Most important, the incorporation of osteoinductive and osteoconductive materials in these systems assists bones proliferation and differentiation, hence the generation of new bone materials is enhanced. Some of these systems can also provide mechanical support for the long bones during the healing process. Most important, if the local systems are designed to be injectable to the affected site and biodegradable, they will reduce the level of invasion required for implantation and can win the patients' compliance and reduce the healing period. They will also allow multiple injections during the course of therapy to guard against the side effect of the long-term systemic therapy. The current review presents different available approaches for delivering antimicrobial agents for the treatment of osteomyelitis focusing on the recent advances in researches for local delivery of antibiotics.HIGHLIGHTSChronic osteomyelitis is a challenging disease due to its serious mortality and morbidity rates and limited effective treatment options.Local drug delivery systems are receiving great attention in the recent decades.Osteoinductive and osteoconductive materials in the local systems assists bones proliferation and differentiationLocal systems can be designed to provide mechanical support for the long bones during the healing process.Designing the local system to be injectable to the affected site and biodegradable will reduces the level of invasion and win the patients' compliance.

Safety of inhaled ivermectin as a repurposed direct drug for treatment of COVID-19: A preclinical tolerance study.

INTRODUCTION: SARS-CoV-2 replication in cell cultures has been shown to be inhibited by ivermectin. However, ivermectin's low aqueous solubility and bioavailabilityhinders its application in COVID-19 treatment. Also, it has been suggested that best outcomes for this medication can be achieved via direct administration to the lung. OBJECTIVES: This study aimed at evaluating the safety of a novel ivermectin inhalable formulation in rats as a pre-clinical step. METHODS: Hydroxy propyl-ß-cyclodextrin(HP-ß-CD) was used to formulate readily soluble ivermectin lyophilized powder. Adult male rats were used to test lung toxicity for ivermectin-HP-ß-CD formulations in doses of 0.05, 0.1, 0.2, 0.4 and 0.8 mg/kg for 3 successive days. RESULTS: The X-ray diffraction for lyophilized ivermectin-HP-ß-CD revealed its amorphous structure that increased drug aqueous solubility 127-fold and was rapidly dissolved within 5 s in saline.Pulmonary administration of ivermectin-HP-ß-CD in dosesof 0.2, 0.4 and 0.8 mg/kgshowed dose-dependent increase in levels of TNF-α, IL-6, IL-13 and ICAM-1 as well as gene expression of MCP-1, protein expression of PIII-NP and serum levels of SP-D paralleled by reduction in IL-10. Moreover, lungs treated with ivermectin (0.2 mg/kg) revealed mild histopathological alterations, while severe pulmonary damage was seen in rats treated with ivermectin at doses of 0.4 and 0.8 mg/kg. However, ivermectin-HP-ß-CD formulation administered in doses of 0.05 and 0.1 mg/kg revealed safety profiles. CONCLUSION: The safety of inhaledivermectin-HP-ß-CD formulation is dose-dependent. Nevertheless, use of low doses(0.05 and 0.1 mg/kg) could be considered as a possible therapeutic regimen in COVID-19 cases.