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1.
Biomed Mater ; 19(2)2024 Jan 19.
Article in English | MEDLINE | ID: mdl-38181448

ABSTRACT

Antimicrobial wound dressings play a crucial role in treatment of wound infections. However, existing commercial options fall short due to antibiotic resistance and the limited spectrum of activity of newly emerging antimicrobials against bacteria that are frequently encountered in wound infections. Antimicrobial photodynamic therapy (aPDT) is very promising alternative therapeutic approach against antibiotic resistant microbes such as methicillin resistantStaphylococcus aureus (MRSA). However, delivery of the photosensitizer (PS) homogeneously to the wound site is a challenge. Though polymeric wound dressings based on synthetic and biopolymers are being explored for aPDT, there is paucity of data regarding theirin vivoefficacy. Moreover, there are no studies on use of PS loaded, pluoronic (PL) and pectin (PC) based films for aPDT. We report development of a polymeric film for potential use in aPDT. The film was prepared using PL and PC via solvent casting approach and impregnated with methylene blue (MB) for photodynamic inactivation of MRSAin vitroandin vivo. Atomic force microscopic imaging of the films yielded vivid pictures of surface topography, with rough surfaces, pores, and furrows. The PL:PC ratio (2:3) was optimized that would result in an intact film but exhibit rapid release of MB in time scale suitable for aPDT. The film showed good antibacterial activity against planktonic suspension, biofilm of MRSA upon exposure to red light. Investigations on MRSA infected excisional wounds of mice reveal that topical application of MB loaded film for 30 min followed by red light exposure for 5 min (fluence; ∼30 J cm-2) or 10 min (fluence; ∼60 J cm-2) reduces ∼80% or ∼92% of bioburden, respectively. Importantly, the film elicits no significant cytotoxicity against keratinocytes and human adipose derived mesenchymal stem cells. Taken together, our data demonstrate that PS-loaded PL-PC based films are a promising new tool for treatment of MRSA infected wounds.


Subject(s)
Anti-Infective Agents , Methicillin-Resistant Staphylococcus aureus , Wound Infection , Animals , Mice , Humans , Methicillin/therapeutic use , Poloxamer/therapeutic use , Methylene Blue/therapeutic use , Pectins/therapeutic use , Photosensitizing Agents , Anti-Bacterial Agents , Polymers , Biofilms , Wound Infection/drug therapy , Wound Infection/microbiology
2.
Carbohydr Polym ; 312: 120822, 2023 Jul 15.
Article in English | MEDLINE | ID: mdl-37059521

ABSTRACT

A mucoadhesive self-assembling polymeric system was developed to carry moxifloxacin (M) for treating bacterial keratitis (BK). Chitosan-PLGA (C) conjugate was synthesized, and poloxamers (F68/127) were mixed in different proportions (1: 5/10) to prepare moxifloxacin (M)-encapsulated mixed micelles (M@CF68/127(5/10)Ms), including M@CF68(5)Ms, M@CF68(10)Ms, M@CF127(5)Ms, and M@CF127(10)Ms. The corneal penetration and mucoadhesiveness were determined biochemically, in vitro using human corneal epithelial (HCE) cells in monolayers and spheroids, ex vivo using goat cornea, and in vivo via live-animal imaging. The antibacterial efficacy was studied on planktonic biofilms of P. aeruginosa and S. aureus (in vitro) and Bk-induced mice (in vivo). Both M@CF68(10)Ms and M@CF127(10)Ms demonstrated high cellular uptake, corneal retention, muco-adhesiveness, and antibacterial effect, with M@CF127(10)Ms exhibiting superior therapeutic effects in P. aeruginosa and S. aureus-infected BK mouse model by reducing the corneal bacterial load and preventing corneal damage. Therefore, the newly developed nanomedicine is promising for clinical translation in treating BK.


Subject(s)
Chitosan , Keratitis , Mice , Humans , Animals , Moxifloxacin/pharmacology , Moxifloxacin/therapeutic use , Micelles , Poloxamer/therapeutic use , Chitosan/pharmacology , Polyglactin 910 , Ophthalmic Solutions/pharmacology , Staphylococcus aureus , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Keratitis/drug therapy , Keratitis/microbiology , Treatment Outcome
3.
Sci Rep ; 12(1): 17429, 2022 10 19.
Article in English | MEDLINE | ID: mdl-36261491

ABSTRACT

Continuous wound infusion with local anesthesia is an effective method for reducing postoperative pain after laparoscopic colorectal surgery. However, most subcutaneous local anesthesia is delivered through continuous injection, which can be inconvenient for patients. This study compared the effectiveness of postoperative pain relief from the application of a local poloxamer 407-based ropivacaine hydrogel (Gel) to the incision site with continuous infusion-type ropivacaine administration (On-Q) in patients undergoing laparoscopic colorectal surgery. This prospective, randomized, non-inferiority study included 61 patients who underwent laparoscopic colorectal surgery with an incision length of 3-6 cm. All 61 patients were randomly assigned to the Gel group (poloxamer 407-based 0.75% ropivacaine, 22.5 mg) or the On-Q group (0.2% ropivacaine, 4 mg/hour for two days). Postoperative analgesia was induced in all patients with intravenous patient-controlled analgesia (IV-PCA). The outcome measures, which were assessed for 72 h after surgery, included the total amount of fentanyl consumed via IV-PCA (primary endpoint), and the amount of rescue analgesia (pethidine) and postoperative pain intensity assessed using a numeric rating scale (NRS) [secondary endpoints]. The Gel was administered to 31 patients and On-Q was used for 30 patients. There was no significant difference in the total usage of fentanyl between the two groups (Gel group, 1623.98 mcg; On-Q group, 1595.12 mcg; P = 0.806). There was also no significant difference in the frequency of analgesic rescue medication use (P = 0.213) or NRS scores (postoperative 6 h, P = 0.860; 24 h, P = 0.333; 48 h, P = 0.168; and 72 h, P = 0.655) between the two groups. The Gel, which continuously delivers a local anesthetic to operative sites, can thus be considered an effective device for analgesia and pain relief for midline incisions in laparoscopic colorectal surgery.


Subject(s)
Anesthetics, Local , Colorectal Surgery , Humans , Anesthetics, Local/therapeutic use , Ropivacaine , Anesthesia, Local/methods , Colorectal Surgery/adverse effects , Prospective Studies , Poloxamer/therapeutic use , Analgesics, Opioid , Analgesia, Patient-Controlled/methods , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Fentanyl , Analgesics/therapeutic use , Meperidine/therapeutic use , Hydrogels/therapeutic use
4.
Adv Sci (Weinh) ; 9(15): e2200872, 2022 05.
Article in English | MEDLINE | ID: mdl-35343104

ABSTRACT

Deferoxamine (DFO) is an FDA-approved iron-chelating agent which shows good therapeutic efficacy, however, its short blood half-life presents challenges such as the need for repeated injections or continuous infusions. Considering the lifelong need of chelating agents for iron overload patients, a sustained-release formulation that can reduce the number of chelator administrations is essential. Here, injectable hydrogel formulations prepared by integrating crosslinked hyaluronic acid into Pluronic F127 for an extended release of DFO nanochelators are reported. The subcutaneously injected hydrogel shows a thermosensitive sol-gel transition at physiological body temperature and provides a prolonged release of renal clearable nanochelators over 2 weeks, resulting in a half-life 47-fold longer than that of the nanochelator alone. In addition, no chronic toxicity of the nanochelator-loaded hydrogel is confirmed by biochemical and histological analyses. This injectable hydrogel formulation with DFO nanochelators has the potential to be a promising formulation for the treatment of iron overload disorders.


Subject(s)
Hydrogels , Iron Overload , Delayed-Action Preparations/therapeutic use , Humans , Iron , Iron Overload/drug therapy , Poloxamer/therapeutic use
5.
Am J Case Rep ; 22: e928021, 2021 Jan 21.
Article in English | MEDLINE | ID: mdl-33473099

ABSTRACT

BACKGROUND Cameron lesions are linear erosions and ulcers on the crests of gastric mucosal folds in the neck of a hiatal hernia and can be difficult to diagnose and treat. This report is of a case of chronic iron deficiency in a 61-year-old woman with a late diagnosis of a Cameron lesion, who did not respond to a single treatment with the proton pump inhibitor (PPI) pantoprazole, but was then treated with oral poloxamer 407 with hyaluronic acid and chondroitin sulfate in addition to PPI. CASE REPORT We report the case of a 61-year-old women with recurrent iron-deficiency anemia, first diagnosed 40 years prior to her presentation at our Endoscopy Unit, and an ongoing melena. We discovered an intrahiatal gastric mucosal defect, which we at first treated with proton pump inhibitors and sucralfate. After a follow-up gastroscopy revealed the persistence of the lesion, we decided to incorporate into the treatment a gel-like substance containing, among others, hyaluronic acid and chondroitin sulfate, and observed that the lesion resolved completely. CONCLUSIONS This report highlights that Cameron lesions should be considered in patients with hiatal hernia who have iron-deficiency anemia and can be diagnosed on upper endoscopy. Further clinical studies are required to determine the role of combined poloxamer 407 with hyaluronic acid and chondroitin sulfate in the management of Cameron lesions.


Subject(s)
Anemia, Iron-Deficiency/drug therapy , Stomach Ulcer/complications , Stomach Ulcer/drug therapy , Adjuvants, Immunologic/therapeutic use , Chondroitin Sulfates/therapeutic use , Chronic Disease , Drug Carriers , Female , Gastroscopy , Hernia, Hiatal/complications , Hernia, Hiatal/diagnosis , Humans , Hyaluronic Acid/therapeutic use , Middle Aged , Pantoprazole/therapeutic use , Poloxamer/therapeutic use , Proton Pump Inhibitors/therapeutic use , Stomach Ulcer/diagnosis
6.
ACS Appl Mater Interfaces ; 12(19): 21231-21241, 2020 May 13.
Article in English | MEDLINE | ID: mdl-31934739

ABSTRACT

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of drug-resistant infections. Its propensity to develop biofilms makes it especially resistant to conventional antibiotics. We present a novel nanoparticle (NP) system made from biocompatible F-127 surfactant, tannic acid (TA), and biguanide-based polymetformin (PMET) (termed FTP NPs), which can kill MRSA biofilm bacteria effectively in vitro and in vivo and which has excellent biocompatibility. FTP NPs exhibit biofilm bactericidal activity-ability to kill bacteria both inside and outside biofilm-significantly better than many antimicrobial peptides or polymers. At low concentrations (8-32 µg/mL) in vitro, FTP NPs outperformed PMET with ∼100-fold (∼2 log10) greater reduction of MRSA USA300 biofilm bacterial cell counts, which we attribute to the antifouling property of the hydrophilic poly(ethylene glycol) contributed by F-127. Further, in an in vivo murine excisional wound model, FTP NPs achieved 1.8 log10 reduction of biofilm-associated MRSA USA300 bacteria, which significantly outperformed vancomycin (0.8 log10 reduction). Moreover, in vitro cytotoxicity tests showed that FTP NPs have less toxicity than PMET toward mammalian cells, and in vivo intravenous injection of FTP NPs at 10 mg/kg showed no acute toxicity to mice with negligible body weight loss and no significant perturbation of blood biomarkers. These biguanide-based FTP NPs are a promising approach to therapy of MRSA infections.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Biofilms/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Nanoparticles/therapeutic use , Poloxamer/therapeutic use , Staphylococcal Infections/drug therapy , Animals , Anti-Bacterial Agents/chemistry , Biguanides/chemistry , Biguanides/therapeutic use , Female , Male , Metformin/analogs & derivatives , Metformin/therapeutic use , Methicillin-Resistant Staphylococcus aureus/physiology , Mice, Inbred BALB C , Mice, Inbred C57BL , Microbial Sensitivity Tests , Nanoparticles/chemistry , Poloxamer/chemistry , Tannins/chemistry , Tannins/therapeutic use
7.
Article in English | MEDLINE | ID: mdl-31192163

ABSTRACT

Antimicrobial peptides, also known as host defense peptides, have recently emerged as a promising new category of therapeutic agents for the treatment of infectious diseases. This study evaluated the preclinical in vitro, ex vivo, and in vivo antimicrobial activity, as well as the potential to cause skin irritation, of human kininogen-derived antimicrobial peptide DPK-060 in different formulations designed for topical delivery. We found that DPK-060 formulated in acetate buffer or poloxamer gel caused a marked reduction of bacterial counts of Staphylococcus aureus in vitro (minimum microbicidal concentration <5 µg/ml). We also found that DPK-060 in poloxamer gel significantly suppressed microbial survival in an ex vivo wound infection model using pig skin and in an in vivo mouse model of surgical site infection (≥99 or ≥94% reduction in bacterial counts was achieved with 1% DPK-060 at 4 h post-treatment, respectively). Encapsulation of DPK-060 in different types of lipid nanocapsules or cubosomes did not improve the bactericidal potential of the peptide under the applied test conditions. No reduction in cell viability was observed in response to administration of DPK-060 in any of the formulations tested. In conclusion, the present study confirms that DPK-060 has the potential to be an effective and safe drug candidate for the topical treatment of microbial infections; however, adsorption of the peptide to nanocarriers failed to show any additional benefits.


Subject(s)
Administration, Topical , Anti-Bacterial Agents/therapeutic use , Antimicrobial Cationic Peptides/therapeutic use , Staphylococcal Infections/drug therapy , Staphylococcus aureus/drug effects , Animals , Anti-Bacterial Agents/administration & dosage , Antimicrobial Cationic Peptides/administration & dosage , Disease Models, Animal , Female , Lipids/chemistry , Mice , Microbial Sensitivity Tests , Nanocapsules , Poloxamer/therapeutic use , Protein Serine-Threonine Kinases/administration & dosage , Protein Serine-Threonine Kinases/pharmacology , Protein Serine-Threonine Kinases/therapeutic use , Skin Irritancy Tests , Staphylococcal Infections/microbiology , Staphylococcal Skin Infections/drug therapy , Swine
8.
Curr Drug Deliv ; 14(7): 926-934, 2017.
Article in English | MEDLINE | ID: mdl-27593184

ABSTRACT

BACKGROUND: Etodolac, a member of non steroidal anti-inflammatory drugs (NSAIDs), has a poor aqueous solubility. Long term administration of etodolac causes severe gastrointestinal disturbances such as peptic ulcer and bleeding. These disturbances could be overcome by alternative routes such as a topical administration. METHOD: In the present study, pluronic lecithin organogels (PLOs) were prepared by simple mixing of pluronic solution with lecithin solution. Etodolac was loaded into the prepared gels or added during the gel formation. The physicochemical properties of the modified organogels were investigated by different analysis including visual inspection, pH determination, viscosity, spreadability and extrudability. Also, the in vitro release studies of etodolac in the presence of different penetration enhancers were carried out. The anti-inflammatory behavior of the prepared etodolac organogel was investigated using carrageenan induced paw edema test. RESULTS: The results indicated that the prepared organogels showed good physicochemical properties. The organogels, containing a combination of tween 80 and oleic acid as penetration enhancers, showed the highest percentage of drug release. CONCLUSION: All tested organogels showed a significant oedema inhibition compared with oral indomethacin ® and Voltaren® as a topical marketed anti-inflammatory drug. Moreover, the increase of drug concentration from 1% to 5% w/w is accompanied with a longer duration of action up to 12 hrs. Therefore, the formulated organogels are considered as a promising vehicle for controlled topical delivery of etodolac.


Subject(s)
Cyclooxygenase 2 Inhibitors/administration & dosage , Drug Delivery Systems , Etodolac/administration & dosage , Lecithins/administration & dosage , Poloxamer/administration & dosage , Administration, Cutaneous , Animals , Carrageenan , Cyclooxygenase 2 Inhibitors/chemistry , Cyclooxygenase 2 Inhibitors/therapeutic use , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/therapeutic use , Drug Liberation , Edema/chemically induced , Edema/drug therapy , Etodolac/chemistry , Etodolac/therapeutic use , Gels , Lecithins/chemistry , Lecithins/therapeutic use , Male , Poloxamer/chemistry , Poloxamer/therapeutic use , Rats , Skin Irritancy Tests
9.
Mil Med ; 181(5 Suppl): 259-64, 2016 05.
Article in English | MEDLINE | ID: mdl-27168582

ABSTRACT

Despite advances in antimicrobial therapies, wound infection remains a global public health concern. We aimed to formulate and assess various nanoemulsions (NEs) for potential effectiveness as stable antimicrobial agents suitable for topic application. A total of 106 NEs were developed that varied with respect to nonionic and cationic surfactants. Stability testing demonstrated that the NEs tested are broadly stable, with 97/106 formulations passing 2-week stability tests. Two NEs, NB-201 and NB-402, were selected to test antimicrobial activity in a wound model in mice. Skin abrasion wounds were infected with Staphylococcus aureus followed by NE treatment. Infected skin was then evaluated by measuring colony forming units. NB-201 reduced median bacterial counts by 4 to 5 log compared to animals treated with saline, whereas NB-402 reduced bacterial counts by 2 to 3 log. Additional stability tests on NB-201 demonstrated that NB-201 is stable in the presence of human serum, and is stable for at least 6 months at 5°C, 25°C, and 40°C. Finally, in in vitro studies, NB-201 was found to be effective against S. aureus at a higher dilution than the commercially available silver sulfadiazine. Altogether these results demonstrate that NB-201 is a stable and effective topical antimicrobial for the treatment of S. aureus.


Subject(s)
Benzalkonium Compounds/pharmacology , Cetylpyridinium/pharmacology , Poloxamer/pharmacology , Polysorbates/pharmacology , Soybean Oil/pharmacology , Staphylococcal Infections/drug therapy , Staphylococcus aureus/drug effects , Animals , Anti-Infective Agents, Local/administration & dosage , Anti-Infective Agents, Local/pharmacology , Anti-Infective Agents, Local/therapeutic use , Benzalkonium Compounds/administration & dosage , Benzalkonium Compounds/therapeutic use , Cetylpyridinium/administration & dosage , Cetylpyridinium/therapeutic use , Drug Combinations , Mice , Models, Animal , Poloxamer/administration & dosage , Poloxamer/therapeutic use , Polysorbates/administration & dosage , Polysorbates/therapeutic use , Silver Sulfadiazine/administration & dosage , Silver Sulfadiazine/pharmacology , Silver Sulfadiazine/therapeutic use , Soybean Oil/administration & dosage , Soybean Oil/therapeutic use , Wound Infection/drug therapy , Wound Infection/prevention & control
10.
Drug Des Devel Ther ; 10: 1101-10, 2016.
Article in English | MEDLINE | ID: mdl-27022248

ABSTRACT

Silymarin is a naturally occurring flavonoid drug; evidence from recent research has highlighted its use as a potential treatment for atopic dermatitis (AD). Both poor water solubility and drug permeability have hindered the percutaneous absorption of silymarin. Formulation of silymarin into pluronic-lecithin organogel (PLO) basis for topical skin delivery is the main aim of this work. Six different PLO formulations were prepared containing various pluronic to lecithin ratios using two cosolvent systems of ethyl alcohol and dimethyl sulfoxide. Formulation 2 (20% pluronic and 3% lecithin) was found to be the optimal base for topical delivery of silymarin as it showed optimum pH, viscosity, drug content, and satisfactory in vitro silymarin permeation. The silymarin PLO formulation significantly relieved inflammatory symptoms of AD such as redness, swelling, and inflammation. These findings warrant the ability for application of these novel silymarin PLO formulations as a novel treatment for AD.


Subject(s)
Dermatitis, Atopic/drug therapy , Gels/therapeutic use , Lecithins/therapeutic use , Poloxamer/therapeutic use , Silymarin/therapeutic use , Adolescent , Adult , Chemistry, Pharmaceutical , Child , Child, Preschool , Drug Stability , Female , Gels/chemistry , Humans , Infant , Lecithins/chemistry , Male , Poloxamer/chemistry , Silymarin/chemistry , Young Adult
11.
Osteoporos Int ; 27(2): 757-67, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26223190

ABSTRACT

UNLABELLED: The ultimate goal of osteoporosis treatment is prevention of fragile fracture. Local treatment targeting specific bone may decrease the incidence of osteoporotic fractures. We developed an injectable, thermosensitive simvastatin/poloxamer 407 hydrogel; a single CT-guided percutaneous intraosseous injection augmented vertebrae in ovariectomized minipigs. INTRODUCTION: The greatest hazard associated with osteoporosis is local fragility fractures. An adjunct, local treatment might be helpful to decrease the incidence of osteoporotic fracture. Studies have found that simvastatin stimulates bone formation, but the skeletal bioavailability of orally administered is low. Directly delivering simvastatin to the specific bone that is prone to fractures may reinforce the target bone and reduce the incidence of fragility fractures. METHODS: We developed an injectable, thermosensitive simvastatin/poloxamer 407 hydrogel, conducted scanning electron microscopy, rheological, and drug release analyses to evaluate the delivery system; injected it into the lumbar vertebrae of ovariectomized minipigs via minimally invasive CT-guided percutaneous vertebral injection. Three months later, BMD, microstructures, mineral apposition rates, and strength were determined by DXA, micro-CT, histology, and biomechanical test; expression of VEGF, BMP2, and osteocalcin were analyzed by immunohistochemistry and Western blots. RESULTS: Poloxamer 407 is an effective controlled delivery system for intraosseous-injected simvastatin. A single injection of the simvastatin/poloxamer 407 hydrogel significantly increased BMD, bone microstructure, and strength; the bone volume fraction and trabecular thickness increased nearly 150 %, bone strength almost doubled compared with controls (all P < 0.01); and induced higher expression of VEGF, BMP2, and osteocalcin. CONCLUSIONS: CT-guided percutaneous vertebral injection of a single simvastatin/poloxamer 407 thermosensitive hydrogel promotes bone formation in ovariectomized minipigs. The underlying mechanism appears to involve the higher expression of VEGF and BMP-2.


Subject(s)
Lumbar Vertebrae/physiopathology , Osteogenesis/drug effects , Osteoporosis/drug therapy , Poloxamer/administration & dosage , Simvastatin/administration & dosage , Absorptiometry, Photon/methods , Animals , Bone Density/drug effects , Bone Morphogenetic Protein 2/metabolism , Chemistry, Physical , Drug Combinations , Drug Delivery Systems , Drug Evaluation, Preclinical/methods , Female , Hydrogel, Polyethylene Glycol Dimethacrylate , Injections, Spinal , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/metabolism , Microscopy, Electron, Scanning , Osteoporosis/diagnostic imaging , Osteoporosis/physiopathology , Ovariectomy , Poloxamer/chemistry , Poloxamer/pharmacology , Poloxamer/therapeutic use , Radiography, Interventional , Rheology , Simvastatin/pharmacology , Simvastatin/therapeutic use , Swine , Swine, Miniature , Tomography, X-Ray Computed , Vascular Endothelial Growth Factor A/metabolism
12.
Int J Hyperthermia ; 27(7): 663-71, 2011.
Article in English | MEDLINE | ID: mdl-21992559

ABSTRACT

PURPOSE: To identify specific Pluronic triblock copolymer structural properties which are critical to its function as a sensitiser in hyperthermia treatment of experimental colorectal adenocarcinoma. MATERIALS AND METHODS: DHD/K12/TRb rat colorectal adenocarcinoma cells were exposed to Pluronics, a family of triblock copolymers with the general structure EO(x)-PO(y)-EO(x) (EO: ethylene oxide, and PO: propylene oxide), at a range of molecular weights (Mw) and EO:PO:EO sub-unit lengths and then submitted to sublethal heat (43°C) treatment. Outcomes indicating Pluronic performance as a thermal sensitiser were correlated with its structural properties; lead candidates were determined accordingly. Finally, one of the lead candidates, Pluronic L61, a 2000 Da copolymer, was used to assess sensitising functionality in vivo in a subcutaneous rat model of colorectal carcinoma. RESULTS: Pluronics with 1100 ≤ Mw ≤ 3200 Da and hydrophilic lipophilic balance (HLB) between 1-8 demonstrated the highest thermosensitising ability. Pluronics L31, L61, L62, L10 and L64 were found to be among the most effective copolymers for hyperthermia sensitisation under tested conditions. Most encouraging, L61 in synergy with hyperthermia significantly reduced tumour growth progression in vivo compared to tumours treated with hyperthermia alone. CONCLUSIONS: Pluronic copolymer structure properties including, Mw, HLB and PO length are essential to its hyperthermia sensitising function.


Subject(s)
Adenocarcinoma/therapy , Colorectal Neoplasms/therapy , Hyperthermia, Induced/methods , Poloxamer/chemistry , Animals , Apoptosis/drug effects , Catheter Ablation , Cell Line, Tumor , Hydrophobic and Hydrophilic Interactions , Male , Molecular Weight , Poloxamer/therapeutic use , Rats
13.
World J Gastroenterol ; 15(24): 2987-94, 2009 Jun 28.
Article in English | MEDLINE | ID: mdl-19554651

ABSTRACT

AIM: To test whether oral L-81 treatment could improve the condition of mice with diabetes and to investigate how L-81 regulates microsomal triglyceride transfer protein (MTP) activity in the liver. METHODS: Genetically diabetic (db/db) mice were fed on chow supplemented with or without L-81 for 4 wk. The body weight, plasma glucose level, plasma lipid profile, and adipocyte volume of the db/db mice were assessed after treatment. Toxicity of L-81 was also evaluated. To understand the molecular mechanism, HepG2 cells were treated with L-81 and the effects on apolipoprotein B (apoB) secretion and mRNA level of the MTP gene were assessed. RESULTS: Treatment of db/db mice with L-81 significantly reduced and nearly normalized their body weight, hyperphagia and polydipsia. L-81 also markedly decreased the fasting plasma glucose level, improved glucose tolerance, and attenuated the elevated levels of plasma cholesterol and triglyceride. At the effective dosage, little toxicity was observed. Treatment of HepG2 cells with L-81 not only inhibited apoB secretion, but also significantly decreased the mRNA level of the MTP gene. Similar to the action of insulin, L-81 exerted its effect on the MTP promoter. CONCLUSION: L-81 represents a promising candidate in the development of a selective insulin-mimetic molecule and an anti-diabetic agent.


Subject(s)
Carrier Proteins/metabolism , Diabetes Mellitus, Experimental/drug therapy , Gene Expression Regulation/drug effects , Poloxamer , Surface-Active Agents , Animals , Carrier Proteins/genetics , Cell Line , Cholesterol/blood , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/physiopathology , Drinking/drug effects , Eating/drug effects , Humans , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Liver/cytology , Liver/drug effects , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Poloxamer/pharmacology , Poloxamer/therapeutic use , Rosiglitazone , Surface-Active Agents/pharmacology , Surface-Active Agents/therapeutic use , Thiazolidinediones/pharmacology , Thiazolidinediones/therapeutic use , Triglycerides/blood , Weight Loss/drug effects
14.
Nurs Stand ; 22(27): 35-9, 2008.
Article in English | MEDLINE | ID: mdl-18405014

ABSTRACT

This information on best practice discusses the evidence on the use of solutions, techniques and pressure in wound cleansing. The article has been reproduced with the permission of the Joanna Briggs Institute (JBI). The article (JBI 2006a), which updates and supersedes the 2003 information sheet of the same name, has been derived from a systematic review conducted in 2004 (Fernandez et al 2004). The primary references on which this information sheet is based are available in the systematic review reports to members of the JBI via the website: www.joannabriggs.edu.au


Subject(s)
Skin Care/methods , Therapeutic Irrigation/methods , Wounds and Injuries/nursing , Benchmarking , Evidence-Based Medicine , Humans , Hydrotherapy , Infection Control , Nursing Evaluation Research , Poloxamer/therapeutic use , Research Design , Skin Care/instrumentation , Skin Care/nursing , Sodium Chloride/therapeutic use , Surface-Active Agents/therapeutic use , Syringes , Therapeutic Irrigation/instrumentation , Therapeutic Irrigation/nursing , Water/administration & dosage , Wound Healing
15.
Ann N Y Acad Sci ; 1077: 256-69, 2006 Sep.
Article in English | MEDLINE | ID: mdl-17124129

ABSTRACT

Intravascular gas embolism can occur with decompression in space flight, and it commonly occurs during cardiac and vascular surgery. Intravascular bubbles may be deposited into any end organ such as the heart or the brain. Surface interactions between the bubble and the endothelial cells lining the vasculature result in serious impairment of blood flow and can lead to heart attack, stroke, or even death. Surfactant-based intervention is a novel treatment for gas embolism. Intravascular surfactant can adsorb onto the gas-liquid interface and compete with blood-borne macromolecules for interfacial occupancy. Surfactants can retard the progress of pathophysiological molecular and cellular events stimulated by the bubble surface, including endothelial cell injury and initiation of blood clotting. Bulk and surface transport of a surfactant to provide competition for interfacial occupancy is a therapeutic strategy because surfactant adsorption can dominate protein (or other macromolecule) adsorption. The presence of surfactant along the gas-liquid interface also induces variation in the interfacial tension, which in turn affects the blood flow and the bubble motion. We describe the interplay between biological transport processes and physiological events occurring and the cellular and molecular level in vascular gas embolization. Special consideration is given to modeling the transport and hydrodynamic interactions associated with surfactant-based intervention.


Subject(s)
Astronauts , Decompression Sickness/complications , Embolism, Air/prevention & control , Extravehicular Activity/adverse effects , Space Flight , Surface-Active Agents/therapeutic use , Adsorption , Animals , Arterioles , Cattle , Computer Simulation , Drug Evaluation, Preclinical , Embolism, Air/etiology , Fluorocarbons/therapeutic use , Hemorheology , Humans , Hydrophobic and Hydrophilic Interactions , Models, Theoretical , Motion , Octoxynol/pharmacology , Organ Culture Techniques , Poloxamer/therapeutic use , Rats , Serum Albumin, Bovine/chemistry , Thrombin/biosynthesis
16.
J Craniofac Surg ; 17(3): 420-5, 2006 May.
Article in English | MEDLINE | ID: mdl-16770175

ABSTRACT

Traditional formulations of bone wax are composed largely of beeswax and are well known to interfere with bone healing and cause inflammatory reactions. Ostene, a newly available bone hemostasis agent made of water-soluble alkylene oxide copolymers, was evaluated. The soft tissue response to Ostene was compared with bone wax and a polyethylene control after implantation into the paravertebral muscles of three rabbits. After 2 weeks, Ostene elicited no fibrous response, the polyethylene elicited a thin (less than 0.5 mm) fibrous response, and the bone wax was encased in a fibrous capsule 0.6 to 1.0 mm thick infiltrated with inflammatory cells. The effects of Ostene were compared with bone wax in a femur defect model in eight rabbits. Ostene showed no evidence of an adverse response in the cortical defect site, medullary cavity, or the surrounding tissue at 4 and 8 weeks. In contrast, bone wax at both time intervals elicited a foreign body response consisting of fibrous tissue infiltrated by macrophages, giant cells, and lymphocytes at the sites of the bone defects. Bone wax also displaced the bone marrow and interfered with bone ingrowth into the defects. Ostene provides the clinician a water-soluble bone hemostasis material that does not demonstrate the adverse tissue response or the interference with bone healing seen with the use of bone wax.


Subject(s)
Hemostatics/therapeutic use , Poloxamer/therapeutic use , Animals , Connective Tissue/pathology , Drug Combinations , Female , Femur/pathology , Femur/surgery , Foreign-Body Reaction/etiology , Giant Cells/pathology , Hemostatics/chemistry , Lymphocytes/pathology , Macrophages/pathology , Muscle, Skeletal/pathology , Muscle, Skeletal/surgery , Osteogenesis/physiology , Palmitates/therapeutic use , Poloxamer/chemistry , Polyethylene/therapeutic use , Polymers/chemistry , Polymers/therapeutic use , Rabbits , Solubility , Time Factors , Water , Waxes/therapeutic use , Wound Healing/physiology
17.
J Interferon Cytokine Res ; 19(1): 67-76, 1999 Jan.
Article in English | MEDLINE | ID: mdl-10048770

ABSTRACT

CRL-1072 is a poloxamer surfactant that kills mycobacteria more effectively within macrophages than in broth cultures. Human macrophages treated with CRL-1072 synthesized interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in a dose-dependent manner. About 3000 pg of IL-8 per million human macrophages accumulated in cultures treated with 100-1500 ng of poloxamer, with mRNA message for IL-8 induced as early as 2 h. As macrophages do not have IL-RA receptors, a transwell culture was used to study the chemotactic and activating effects of IL-8 between CRL-1072-treated human macrophage effectors and polymorphonuclear neutrophil (PMN) targets. PMN were activated by IL-8 and secreted hydrogen peroxide and myeloperoxidase (MPO). MPO derived from PMN, in turn, activated monocytes for an enhanced killing of intracellular Mycobacterium avium. The ability of CRL-1072 to modulate macrophage-mediated activation of neutrophils and receive a feedback activation signal may form one mechanism by which its antimycobacterial activity is achieved in vivo.


Subject(s)
Interleukin-8/biosynthesis , Macrophages/drug effects , Mycobacterium avium/drug effects , Poloxamer/therapeutic use , Surface-Active Agents/therapeutic use , Granulocyte-Macrophage Colony-Stimulating Factor/biosynthesis , Humans , Hydrogen Peroxide/metabolism , Macrophages/immunology , Microbial Sensitivity Tests , Monocytes/drug effects , Mycobacterium avium/immunology , Neutrophils/drug effects , Peroxidase/blood , Tumor Necrosis Factor-alpha/biosynthesis , U937 Cells
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