-
ACS Omega Jun 2024Core/shell nanofibers offer the advantage of encapsulating multiple drugs with different hydrophilicity in the core and shell, thus allowing for the controlled release...
Core/shell nanofibers offer the advantage of encapsulating multiple drugs with different hydrophilicity in the core and shell, thus allowing for the controlled release of pharmaceutic agents. Specifically, the burst release of hydrophilic drugs from such fiber membranes causes an instantaneous high drug concentration, whereas a long and steady release is usually desired. Herein, we tackle the problem of the initial burst release by the generation of core/shell nanofibers with the hydrophilic antibiotic drug gentamycin loaded within a hydrophilic alginate core surrounded by a hydrophobic shell of poly(ε-caprolactone). Emulsion electrospinning was used as the nanofibrous mesh generation procedure. This process also allows for the loading of a hydrophobic compound, where we selected a natural antioxidant molecule, betulin (BTL), to detoxify the radicals. The resulting nanofibers exhibited a cylindrical shape with a core/shell structure. tests showed a controlled release of gentamicin from nanofibers via diffusion. The drug reached 93% release in an alginate hydrogel film but only 50% release in the nanofibers, suggesting its potential to minimize the initial burst release. Antibacterial tests revealed significant activity against both Gram-negative and Gram-positive bacteria. The antioxidant property of betulin was confirmed through the DPPH assay, where the incorporation of 20% BTL revealed 37.3% DPPH scavenging. The nanofibers also exhibited favorable biocompatibility in cell culture studies, and no harmful effects on cell viability were observed. Overall, this research offers a promising approach to producing core/shell nanofibrous mats with antibacterial and antioxidant properties, which could effectively address the requirements of wound dressings, including infection prevention and wound healing acceleration.
PubMed: 38882148
DOI: 10.1021/acsomega.4c02510 -
Journal of Controlled Release :... Jun 2024Transarterial chemoembolization (TACE) is the standard of care for patients with advanced hepatocellular carcinoma (HCC), but facing the problem of low therapeutic...
Transarterial chemoembolization (TACE) is the standard of care for patients with advanced hepatocellular carcinoma (HCC), but facing the problem of low therapeutic effect. Conventional TACE formulations contain Lipiodol (LP) and chemotherapeutic agents characterized by burst release due to the unstable emulsion. Herein, we developed a novel TACE system by inducing bovine serum albumin (BSA) loaded hypoxia-activated prodrug (tirapazamine, TPZ) nanoparticle (BSA) for sustained drug release. In the rabbit VX2 liver cancer model, TACE treatment induced a long-term hypoxic tumor microenvironment as demonstrated by increased expression of HIF-1α in the tumor. BSA nanoparticles combined with LP greatly enhanced the anti-tumor effects of the TACE treatment. Compared to conventional TACE treatment, BSA nanoparticle-based TACE therapy more significantly delayed tumor progression and inhibited the metastases in the lungs. The effects could be partially mediated by the rebuilt immune responses, as BSA nanoparticle can served as an immunogenic cell death (ICD) inducer. Collectively, our results suggest that BSA nanoparticle-based TACE therapy could be a promising strategy to improve clinical outcomes for patients with HCC and provide a preclinical rationale for evaluating TPZ therapy in clinical studies.
PubMed: 38879131
DOI: 10.1016/j.jconrel.2024.06.026 -
Colloids and Surfaces. B, Biointerfaces Jun 2024Liuwei Dihuang (LWDH) is a multi-component and multi-target Chinese herbal compound widely used for treating chronic conditions such as diabetes, diabetic nephropathy,...
Liuwei Dihuang (LWDH) is a multi-component and multi-target Chinese herbal compound widely used for treating chronic conditions such as diabetes, diabetic nephropathy, hypertension, osteoporosis, and chronic kidney disease. However, traditional Chinese medicine (TCM) preparations like decoction and pill face limitations, including low active component concentration, limited bioavailability, short half-life, and the need for high dosage, which may increase the burden on liver and kidney functions and reduce clinical efficacy. In this study, LWDH was further purified using D101 macroporous adsorption resin, resulting in a soluble extract with an active component content 53.6 times higher than that of LWDH itself. The freeze-dried LWDH extract was then encapsulated within silk fibroin (SF) microspheres to significantly enhance the sustained release performance of the drug. In a human umbilical vein endothelial cell (HUVEC) model cultured under high glucose conditions, methanol vapor-treated SF/LWDH microspheres demonstrated a decrease in the 24-hour drug release rate from 61.88 % to 34.81 %, augmenting their protective effect on endothelial cells.
PubMed: 38878662
DOI: 10.1016/j.colsurfb.2024.114034 -
Carbohydrate Polymers Oct 2024The use of Pickering emulsions for biocatalysis is gaining increased attention. However, the extensive application is greatly limited due to the enzyme inactivation....
The use of Pickering emulsions for biocatalysis is gaining increased attention. However, the extensive application is greatly limited due to the enzyme inactivation. Herein, a biocatalytic Pickering emulsion with high-performance utilizing cellulose nanocrystals immobilized lipases (CNCs-Lps) particles as stabilizer is advanced and applied for the synthesis of Vitamin E nicotinate. CNCs-Lps display high activity and reusability due to the construction of biocatalytic microreactor in the O/W emulsion system. The yield of vitamin E nicotinate ester reached up to 83 %. More importantly, the CNCs-Lps can be reused due to the similar principles to microreactors in Pickering emulsions. Reusability test showed that the CNCs-Lps could be recovered from the emulsion system by centrifugation and the yield of vitamin E nicotinate retains 78 % of initial value after five cycles, demonstrating overwhelming advantage than the fair counterpart with free lipases.
Topics: Cellulose; Emulsions; Lipase; Nanoparticles; Biocatalysis; Enzymes, Immobilized; Vitamin E
PubMed: 38876720
DOI: 10.1016/j.carbpol.2024.122353 -
International Journal of Pharmaceutics Jun 2024Tranexamic acid (TXA) is an anti-fibrinolysis agent widely used in postoperative blood loss management. As a highly water-soluble drug, TXA is suffering from rapid...
Tranexamic acid (TXA) is an anti-fibrinolysis agent widely used in postoperative blood loss management. As a highly water-soluble drug, TXA is suffering from rapid clearance from the action site, therefore, large amount of drug is required when administered either by intravenously or topically. In this study, a TXA preparation with prolonged action site residence was designed using the nano-micro strategy. TXA nanoparticles were dispersed in oil by emulsification followed by lyophilization to give a solid-in-oil suspension, which was used as the oil phase for the preparation of TXA-loaded solid-in-oil-in-water (TXA@S/O/W) system. The particle size of TXA in oil was 207.4 ± 13.50 nm, and the particle size of TXA@S/O/W was 40.5 μm. The emulsion-in-gel system (TXA@S/O/G) was prepared by dispersing TXA@S/O/W in water solution of PLGA-b-PEG-b-PLGA (PPP). And its gelling temperature was determined to be 26.6 ℃ by a rheometer. Sustained drug release was achieved by TXA@S/O/G with 72.85 ± 7.52 % of TXA released at 120 h. Formulation retention at the joint cavity was studied by live imaging, and the fluorescent signals dropped gradually during one week. Drug escape from the injection site via drainage and absorption was investigated by a self-made device and plasma TXA concentration determination, respectively. TXA@S/O/G showed the least drug drainage during test, while more than 70 % of drug was drained in TXA@S/O/W group and TXA solution group. Besides, low yet steady plasma TXA concentration (less than 400 ng/mL) was found after injecting TXA@S/O/G into rat knees at a dosage of 2.5 mg/kg, which was much lower than those of TXA dissolved in PPP gel or TXA solution. In conclusion, sustained drug release as well as prolonged action site retention were simultaneously achieved by the designed TXA@S/O/G system. More importantly, due to the steady plasma concentration, this strategy could be further applied to other highly water-soluble drugs with needs on sustained plasma exposure.
PubMed: 38871135
DOI: 10.1016/j.ijpharm.2024.124334 -
Current Pharmaceutical Biotechnology Jun 2024Oleogelation is an efficient and emerging approach for obtaining biocompatible and biodegradable elastic semisolid crystals to be used in various cosmetic and...
BACKGROUND
Oleogelation is an efficient and emerging approach for obtaining biocompatible and biodegradable elastic semisolid crystals to be used in various cosmetic and pharmaceutical formulations. Recently, drug incorporation in oil structuring has been a promising strategy under consideration due to the effectiveness of this method. Plant oils have very beneficial characteristics for skin care and wound healing due to the presence of certain antioxidants.
METHODS
In this study, the oleogels of Moringa oleifera seed oil with natural polysaccharides, including pectin, chitosan, and xanthan gum, were prepared using the emulsion template method. Moringa oil was selected because it can hydrate and moisturize the skin and has great antioxidant activity. Also, the natural polysaccharides, i.e., pectin and chitosan, exhibited good gelling properties. Allantoin, which is a wound healer and eucalyptus leaf oil with antioxidant potential, was incorporated into the emulsion-based-oleogels to enhance the antioxidant and antimicrobial activity of the oleogels.
RESULTS
Allantoin and eucalyptus-loaded oleogels exhibited good antibacterial activity against E. coli. The FTIR spectra of moringa-based oleogels in the range between 3226-3422 cm-1 indicate the presence of hydrogen bonding in oleogels.
CONCLUSION
The antioxidant potential of allantoin and eucalyptus-containing oleogel was maximized, and an IC50 value of 0.9719 μM was found. Maximum release of allantoin from oleogel was observed in the first hour.
PubMed: 38867525
DOI: 10.2174/0113892010295050240508114723 -
BMC Veterinary Research Jun 2024Acetamiprid (ACDP) is a widely used neonicotinoid insecticide that is popular for its efficacy in controlling fleas in domestic settings and for pets. Our study aims to...
Cinnamon nanoemulsion mitigates acetamiprid-induced hepatic and renal toxicity in rats: biochemical, histopathological, immunohistochemical, and molecular docking analysis.
Acetamiprid (ACDP) is a widely used neonicotinoid insecticide that is popular for its efficacy in controlling fleas in domestic settings and for pets. Our study aims to offer a comprehensive examination of the toxicological impacts of ACDP and the prophylactic effects of cinnamon nanoemulsions (CMNEs) on the pathological, immunohistochemical, and hematological analyses induced by taking ACDP twice a week for 28 days. Forty healthy rats were divided into four groups (n = 10) at random; the first group served as control rats; the second received CMNEs (2 mg/Kg body weight); the third group received acetamiprid (ACDP group; 21.7 mg/Kg body weight), and the fourth group was given both ACDP and CMNEs by oral gavage. Following the study period, tissue and blood samples were extracted and prepared for analysis. According to a GC-MS analysis, CMNEs had several bioactive ingredients that protected the liver from oxidative stress by upregulating antioxidant and anti-inflammatory agents. Our findings demonstrated that whereas ACDP treatment considerably boosted white blood cells (WBCs) and lymphocytes, it significantly lowered body weight gain (BWG), red blood cells (RBCs), hemoglobin (Hb), hematocrit (HCT), and platelets (PLT). ACDP notably reduced antioxidant enzyme activities: superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) and elevated hydrogen peroxide and malondialdehyde levels compared with other groups. ACDP remarkably raised alanine aminotransferase (ALT), aspartate amino transaminase (AST), and alkaline phosphatase (ALP) levels.Moreover, the histopathological and immunohistochemistry assays discovered a severe toxic effect on the liver and kidney following ACDP delivery. Furthermore, cyclooxygenase 2 (COX-2) + immunoexpression was enhanced after treatment with CMNEs. All of the parameters above were returned to nearly normal levels by the coadministration of CMNEs. The molecular docking of cinnamaldehyde with COX-2 also confirmed the protective potential of CMNEs against ACDP toxicity. Our findings highlighted that the coadministration of CMNEs along with ACDP diminished its toxicity by cutting down oxidative stress and enhancing antioxidant capacity, demonstrating the effectiveness of CMNEs in lessening ACDP toxicity.
Topics: Animals; Neonicotinoids; Cinnamomum zeylanicum; Insecticides; Rats; Emulsions; Molecular Docking Simulation; Male; Liver; Kidney; Oxidative Stress; Chemical and Drug Induced Liver Injury; Antioxidants; Kidney Diseases; Rats, Sprague-Dawley
PubMed: 38867202
DOI: 10.1186/s12917-024-04084-x -
International Journal of Biological... Jun 2024This research focuses on the challenges of efficiently constructing drug carriers and evaluating their dynamic release in vitro simulation. By using pickering emulsion...
This research focuses on the challenges of efficiently constructing drug carriers and evaluating their dynamic release in vitro simulation. By using pickering emulsion and layer-by-layer self-assembly methods. The microcapsules had tea tree oil as the core material, SiO nanoparticles as stabilizers, and chitosan and hyaluronic acid as shell materials. The microencapsulation mechanism, as well as the effects of core-shell mass ratio and stirring, were discussed. Specifically, a dynamic circulation simulation microchannel system was designed and manufactured based on 3D printing technology. In this simulation system, the release rate of microcapsules is accelerated and the trend changes, with its behavior aligning with the Boltzmann model. The study demonstrates the advantages of self-assembled inorganic-organic drug-loaded microcapsules in terms of controllable fabrication and ease of functional modification, and shows the potential of 3D printed cyclic microchannel systems in terms of operability and simulation fidelity in drug and physiological analysis.
PubMed: 38866283
DOI: 10.1016/j.ijbiomac.2024.133031 -
The AAPS Journal Jun 2024Addressing the intertwined challenges of antimicrobial resistance and impaired wound healing in diabetic patients, an oil/water emulsion-based nano-ointment integrating...
Addressing the intertwined challenges of antimicrobial resistance and impaired wound healing in diabetic patients, an oil/water emulsion-based nano-ointment integrating phenylpropanoids-Eugenol and Cinnamaldehyde-with positively-charged silver nanoparticles was synthesized. The process began with the synthesis and characterization of nano-silver, aimed at ensuring the effectiveness and safety of the nanoparticles in biological applications. Subsequent experiments determined the minimum inhibitory concentration (MIC) against pathogens such as Streptococcus aureus, Pseudomonas aeruginosa and Candida albicans. These MIC values of all three active leads guided the strategic formulation of an ointment base, which effectively integrated the bioactive components. Evaluations of this nano-ointment revealed enhanced antimicrobial activity against both clinical and reference bacterial strains and it maintained stability after freeze-thaw cycles. Furthermore, the ointment demonstrated superior in-vitro diabetic wound healing capabilities and significantly promoted angiogenesis, as shown by enhanced blood vessel formation in the Chorioallantoic Membrane assay. These findings underscore the formulation's therapeutic potential, marking a significant advance in the use of nanotechnology for topical wound care.
Topics: Silver; Wound Healing; Microbial Sensitivity Tests; Metal Nanoparticles; Animals; Ointments; Acrolein; Candida albicans; Anti-Infective Agents; Pseudomonas aeruginosa; Administration, Topical; Humans; Anti-Bacterial Agents; Staphylococcus aureus
PubMed: 38862870
DOI: 10.1208/s12248-024-00936-4 -
AAPS PharmSciTech Jun 2024Cannabidiol (CBD) is a highly lipophilic compound with poor oral bioavailability, due to poor aqueous solubility and extensive pre-systemic metabolism. The aim of this...
Cannabidiol (CBD) is a highly lipophilic compound with poor oral bioavailability, due to poor aqueous solubility and extensive pre-systemic metabolism. The aim of this study was to explore the potential of employing Hot Melt Extrusion (HME) technology for the continuous production of Self Emulsifying Drug Delivery Systems (SEDDS) to improve the solubility and in vitro dissolution performance of CBD. Accordingly, different placebos were processed through HME in order to obtain a lead CBD loaded solid SEDDS. Two SEDDS were prepared with sesame oil, Poloxamer 188, Gelucire59/14, PEO N80 and Soluplus. Moreover, Vitamin E was added as an antioxidant. The SEDDS formulations demonstrated emulsification times of 9.19 and 9.30 min for F1 and F2 respectively. The formed emulsions showed smaller droplet size ranging from 150-400 nm that could improve lymphatic uptake of CBD and reduce first pass metabolism. Both formulations showed significantly faster in vitro dissolution rate (90% for F1 and 83% for F2) compared to 14% for the pure CBD within the first hour, giving an enhanced release profile. The formulations were tested for stability over a 60-day time period at 4°C, 25°C, and 40°C. Formulation F1 was stable over the 60-day time-period at 4°C. Therefore, the continuous HME technology could replace conventional methods for processing SEDDS and improve the oral delivery of CBD for better therapeutic outcomes.
Topics: Cannabidiol; Emulsions; Drug Delivery Systems; Solubility; Administration, Oral; Chemistry, Pharmaceutical; Hot Melt Extrusion Technology; Drug Liberation; Particle Size; Biological Availability; Drug Compounding; Polyethylene Glycols; Drug Stability; Sesame Oil; Polyvinyls
PubMed: 38862810
DOI: 10.1208/s12249-024-02857-z