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1.
Sci Rep ; 11(1): 19457, 2021 09 30.
Article in English | MEDLINE | ID: mdl-34593866

ABSTRACT

The study aimed to evaluate a commercial blend of functional oils based on liquid from the cashew nutshell and castor oil as a growth promoter in newly weaned piglets. A total of 225 piglets, castrated males and females with 28 days of age were randomly distributed in pens with 15 animals composing three treatments and five repetitions. The treatments were: control (without the inclusion of additives), probiotics, or functional oils. The performance was evaluated. At 50 days of age, a pool of fresh feces from 3 animals/repetition was collected to perform the sequencing of microbiota using the Illumina MiSeq platform. Supplementation with functional oils improved the piglets' daily weight gain and feed conversion ratio (P < 0.05) in the first weeks of the experiment, which resulted in higher final live weight (P < 0.05) in the phase when compared to the control treatment (24.34 kg and 21.55 kg, respectively). The animals that received probiotics showed an intermediate performance (23.66 kg final live weight) at the end of the 38 experimental days. Both additives were effective in increasing groups essential for intestinal health, such as Ruminococcaceae and Lachnospiraceae. The functional oils were more effective in reducing pathogenic bacteria, such as Campylobacter and Escherichia coli. In conclusion, the use of functional oils optimized performance and effectively modulated the microbiota of newly weaned piglets.


Subject(s)
Diet/veterinary , Gastrointestinal Microbiome/drug effects , Plant Oils/administration & dosage , Probiotics/administration & dosage , Anacardium/chemistry , Animal Feed/analysis , Animals , Bacteria/genetics , Bacteria/isolation & purification , Castor Oil/administration & dosage , Female , Male , Sequence Analysis, DNA , Sus scrofa/growth & development , Sus scrofa/microbiology
2.
Int Arch Allergy Immunol ; 181(5): 385-394, 2020.
Article in English | MEDLINE | ID: mdl-32259823

ABSTRACT

BACKGROUND: Drug-free viscous nasal applications have been shown to reduce nasal symptoms in individuals with seasonal allergic rhinitis (SAR). Nascum®-Plus (NP), a commercially available thixotropic gel, has been designed to reduce dryness and soreness of the nasal mucosa and prevent the absorption of small particles. OBJECTIVES: The aim of this study was to assess the efficacy of single-dose NP in treating nasal symptoms and secretion during challenge in an allergen challenge chamber (ACC). Furthermore, the effect of this treatment on biomarkers and immune cells of the allergic cascade were measured. METHODS: This open-label, cross-over, sequence-randomized, monocentric trial randomized 18 adults with SAR and a positive skin prick test reaction to Dactylis glomerata pollen to receive NP or no treatment during two 4-h ACC sessions 3 weeks apart. On Day 1, 9 subjects were challenged for 4 h with treatment, the other 9 without treatment, and vice versa on Day 22. Nasal lavage fluid and nasal filter eluate samples were obtained pre, 2, and 18 h post challenge in the ACC. RESULTS: NP significantly reduced nasal symptoms, assessed by total nasal symptom score (p < 0.001), and minimized nasal secretion (p = 0.047), while no significant effect on biomarkers and immune cells in the nasal fluid was observed. The treatment was safe and well-tolerated. CONCLUSIONS: The physical barrier built by NP nasal gel can be safely applied in patients with allergic rhinitis. It reduces allergic nasal symptoms and secretion, but application of a single dose does not affect local inflammatory biomarkers.


Subject(s)
Castor Oil/administration & dosage , Nasal Mucosa/drug effects , Rhinitis, Allergic, Seasonal/immunology , Rhinitis, Allergic, Seasonal/prevention & control , Silicon Dioxide/administration & dosage , Administration, Intranasal , Adult , Biomarkers , Colloids , Female , Gels , Humans , Inflammation/immunology , Inflammation/prevention & control , Male , Middle Aged , Nasal Mucosa/immunology
3.
Molecules ; 25(4)2020 Feb 24.
Article in English | MEDLINE | ID: mdl-32102361

ABSTRACT

The aim of the present study was to evaluate the possible gut inhibitory role of the phosphodiesterase (PDE) inhibitor roflumilast. Increasing doses of roflumilast were tested against castor oil-induced diarrhea in mice, whereas the pharmacodynamics of the same effect was determined in isolated rabbit jejunum tissues. For in silico analysis, the identified PDE protein was docked with roflumilast and papaverine using the Autodock vina program from the PyRx virtual screening tool. Roflumilast protected against diarrhea significantly at 0.5 and 1.5 mg/kg doses, with 40% and 80% protection. Ex vivo findings from jejunum tissues show that roflumilast possesses an antispasmodic effect by inhibiting spontaneous contractions in a concentration-dependent manner. Roflumilast reversed carbachol (CCh, 1 µM)-mediated and potassium (K+, 80 mM)-mediated contractile responses with comparable efficacies but different potencies. The observed potency against K+ was significantly higher in comparison to CCh, similar to verapamil. Experiments were extended to further confirm the inhibitory effect on Ca++ channels. Interestingly, roflumilast deflected Ca++ concentration-response curves (CRCs) to the right with suppression of the maximum peak at both tested doses (0.001-0.003 mg/mL), similar to verapamil. The PDE-inhibitory effect was authenticated when pre-incubation of jejunum tissues with roflumilast (0.03-0.1 mg/mL) produced a leftward deflection of isoprenaline-mediated inhibitory CRCs and increased the tissue level of cAMP, similar to papaverine. This idea was further strengthened by molecular docking studies, where roflumilast exhibited a better binding affinity (-9.4 kcal/mol) with the PDE protein than the standard papaverine (-8.3 kcal/mol). In conclusion, inhibition of Ca++ channels and the PDE-4 enzyme explains the pharmacodynamics of the gut inhibitory effect of roflumilast.


Subject(s)
Aminopyridines/pharmacology , Antidiarrheals/pharmacology , Benzamides/pharmacology , Calcium Channel Blockers/pharmacology , Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism , Diarrhea/prevention & control , Parasympatholytics/pharmacology , Phosphodiesterase 4 Inhibitors/pharmacology , Aminopyridines/chemistry , Aminopyridines/pharmacokinetics , Animals , Antidiarrheals/chemistry , Antidiarrheals/pharmacokinetics , Benzamides/chemistry , Benzamides/pharmacokinetics , Binding Sites , Calcium Channel Blockers/chemistry , Calcium Channel Blockers/pharmacokinetics , Carbachol/pharmacology , Castor Oil/administration & dosage , Cyclic AMP/metabolism , Cyclic Nucleotide Phosphodiesterases, Type 4/chemistry , Cyclopropanes/chemistry , Cyclopropanes/pharmacokinetics , Cyclopropanes/pharmacology , Diarrhea/chemically induced , Diarrhea/metabolism , Diarrhea/physiopathology , Isoproterenol/pharmacology , Jejunum/drug effects , Jejunum/metabolism , Mice , Molecular Docking Simulation , Papaverine/pharmacology , Parasympatholytics/chemistry , Parasympatholytics/pharmacokinetics , Phosphodiesterase 4 Inhibitors/chemistry , Phosphodiesterase 4 Inhibitors/pharmacokinetics , Protein Binding , Protein Interaction Domains and Motifs , Protein Structure, Secondary , Rabbits , Verapamil/pharmacology
4.
Int J Pharm ; 575: 118935, 2020 Feb 15.
Article in English | MEDLINE | ID: mdl-31816353

ABSTRACT

Novel liquid crystal nanoparticles (LCNs) composed of isostearyl glyceryl ether (GE-IS) and ethoxylated hydrogenated castor oil (HCO-60) were developed for the enhanced transdermal delivery of 4-biphenyl acetic acid (BAA). The physical properties and pharmaceutical properties of the LCNs were measured. The interaction between the intercellular lipid model of the stratum corneum and the LCNs was observed to elucidate the skin permeation mechanism. In the formulation, the LCNs form niosomes with mean particles sizes of 180-300 nm. The skin absorption mechanisms of LCNs are different, depending upon the application and buffer concentration. The LCNs composed of GE-IS and HCO-60 are attractive tools for use as transdermal drug delivery systems carriers for medicines and cosmetics, due to their high efficiency and safety.


Subject(s)
Drug Delivery Systems , Glyceryl Ethers/administration & dosage , Liquid Crystals , Nanoparticles/administration & dosage , Phenylacetates/administration & dosage , Administration, Cutaneous , Animals , Castor Oil/administration & dosage , Castor Oil/chemistry , Drug Liberation , Glyceryl Ethers/chemistry , Humans , In Vitro Techniques , Liquid Crystals/chemistry , Male , Mice, Hairless , Nanoparticles/chemistry , Phenylacetates/chemistry , Skin/metabolism , Skin Absorption , Skin Irritancy Tests
5.
Int J Pharm ; 567: 118478, 2019 Aug 15.
Article in English | MEDLINE | ID: mdl-31260782

ABSTRACT

To encapsulate and deliver poorly water-soluble drugs, castor oil/silica hybrid microparticles (HMP)s were synthesized. Green chemistries were used to silylate the oil and further cross-link it into solid microparticles by sol-gel reaction. Silylated castor oils (ICO)s at various silylation ratios were prepared and allowed the solubilization of ibuprofen at several concentrations up to 16 wt%. The HMPs were formulated by ThermoStabilized Emulsion (TSE) process which permits to "freeze" the oil-in-water emulsion while the sol-gel reaction occurs. The hybrid mineral/organic composition and the morphology (spherical shape and micrometric size) of these HMPs were determined by complementary technics (SEM, TGA, EDX, 29Si NMR and FTIR spectroscopies). The HMPs reached a good ibuprofen loading efficiency regardless to the formulation used while the release kinetics in simulated oral administration exhibited a tunable release during 3 h according to the silylation ratio. The ibuprofen rate also influenced its own amorphous or crystalline character within the HMPs. For subcutaneous conditions, ibuprofen release took place over 15 days. Finally, biodegradability assays in simulated digestion medium suggested a surface-limited hydrolysis of the particles and cytocompatibility studies on NIH-3T3 and Caco-2 cells demonstrated an excellent cellular viability.


Subject(s)
Castor Oil/administration & dosage , Drug Carriers/administration & dosage , Silicon Dioxide/administration & dosage , Administration, Oral , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Caco-2 Cells , Castor Oil/chemistry , Cell Survival/drug effects , Drug Carriers/chemistry , Drug Liberation , Humans , Ibuprofen/administration & dosage , Ibuprofen/chemistry , Mice , NIH 3T3 Cells , Silicon Dioxide/chemistry , Solubility , Water/chemistry
6.
Poult Sci ; 98(11): 5855-5861, 2019 Nov 01.
Article in English | MEDLINE | ID: mdl-31329962

ABSTRACT

As antioxidants such as some functional oils are good candidates to mitigate heat stress, a commercial blend of functional oils (Essential, Oligo Basics USA LLC, Cary, NC; active ingredients: cashew nut shell oil and castor oil) was used to study the effects of two ambient temperatures (moderate and high) on broiler chicken performance and carcass parameters. A total of 2,240 straight-run one-day-old chickens were sorted by weight, randomized among 28 floor pens with 80 chickens per pen and 7 replicates for each treatment. Birds were assigned to one of 4 dietary treatments in a 2 × 2 factorial arrangement with two temperature environments (moderate and high) and without or with Essential supplementation (1.5 kg/ton). Variances for the average temperature, relative humidity, and dew point for the two environments were different (P < 0.001), showing that the high-temperature environment reached higher temperatures and dew points. Essential supplementation increased body weight gain at 42 D of age (2.548 vs. 2.508 kg; P < 0.01) and tended to improve feed conversion (1.621 vs. 1.644; P = 0.09) independent of temperature environment. The high-temperature environment increased mortality (7.5 vs. 12.4%; P = 0.03) and carcass yields (77.5 vs. 76.2%; P < 0.01). Breast yields were affected by an environment by Essential interaction (P < 0.01). Whereas the high-temperature environment decreased breast yield in control birds, it did not decrease breast yield in birds supplemented with Essential. Finally, breast yields were increased by Essential supplementation (23.6 vs. 22.9%; P < 0.01) regardless of the ambient temperature. In conclusion, Essential supplementation improved weight gains and carcass characteristics, and high-temperature environments decreased breast yields when Essential was not supplemented.


Subject(s)
Anacardium/chemistry , Castor Oil/metabolism , Chickens/physiology , Hot Temperature , Meat/analysis , Plant Oils/metabolism , Animal Feed/analysis , Animals , Castor Oil/administration & dosage , Chickens/growth & development , Diet/veterinary , Dietary Supplements/analysis , Male , Plant Oils/administration & dosage
7.
AAPS PharmSciTech ; 20(2): 66, 2019 Jan 09.
Article in English | MEDLINE | ID: mdl-30627825

ABSTRACT

Despite the great potential of peptides as therapeutics, there is an unmet challenge in sustaining delivery of sufficient amounts in their native forms. This manuscript describes a novel nanocarrier capable of delivering functional small peptides in its native form. Self-assembling multi-layered nanomicelles composed of two polymers, polyoxyethylene hydrogenated castor oil 40 (HCO-40) and octoxynol 40 (OC-40), were designed to combine hydrophilic interaction and solvent-induced encapsulation of peptides and proteins. The polymers are employed to encapsulate peptide or protein in the core of the organo-nanomicelles which are further encapsulated with another layer of the same polymers to form an aqueous stable nanomicellar solution. The size of the multi-layered nanomicelles ranges from ~ 16 to 20 nm with zeta potential close to neutral (~ - 2.44 to 0.39 mV). In vitro release studies revealed that octreotide-loaded multi-layered nanomicelles released octreotide at much slower rate in simulated tear fluid (STF) (~ 27 days) compared to PBST (~ 11 days) in its native form. MTT assay demonstrated negligible toxicity of the multi-layered nanomicelles at lower concentrations in human retinal pigment epithelial (HRPE, D407), human conjunctival epithelial (CCL 20.2), and rhesus choroid-retinal endothelial (RF/6A) cells. This work demonstrates an efficient small peptide delivery platform with significant advantages over existing approaches, as it does not require modification of the peptide, is biodegradable, and has a small size and high loading capacity.


Subject(s)
Drug Delivery Systems/methods , Micelles , Nanoparticles/administration & dosage , Peptides/administration & dosage , Retinal Pigment Epithelium/drug effects , Administration, Ophthalmic , Animals , Castor Oil/administration & dosage , Castor Oil/chemistry , Castor Oil/metabolism , Cell Line , Humans , Hydrophobic and Hydrophilic Interactions , Macaca mulatta , Nanoparticles/chemistry , Nanoparticles/metabolism , Peptides/chemistry , Peptides/metabolism , Retinal Pigment Epithelium/metabolism
8.
Medicine (Baltimore) ; 97(17): e0481, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29703007

ABSTRACT

Colonoscopy has been regarded as an important method of early diagnosing and treating gastrointestinal lesions; however adequate bowel preparation is critical one of many factors needed for successful colonoscopy. Although several modified or novel regimes have been developed, desired quality of bowel preparation has not yet been generated. Scattered evidences revealed that castor oil may have potential of effectively cleansing colon. It is noted that, however, prospective trial of exploring the value of castor oil in preparing bowel before colonoscopy is lacking. The aims of this study are to test the hypotheses that low dose castor oil (30 mL) may enhance potential of polyethylene glycol (PEG) and combination of low castor oil and ascorbic acid may halve the volume of PEG.This is a randomized, double-blind (endoscopist and assessor), single center trial with three-arm design. We will randomly assign 282 adult patients (≥18 years but < 75 years), who are scheduled to undergo colonoscopy, to receive either 3 L PEG alone, 2 L PEG plus 30 mL castor oil or combination of 1 L PEG, 30 mL castor oil and 5 g ascorbic acid. The bowel preparation quality based on Boston Bowel Preparation Scale (BBPS) is the primary outcome. The secondary outcomes include the first defecation time, total number of defecation, time of cecal intubation, detection rate of polyp and adenoma, willing to repeat the same regime, tolerance to regime, and adverse events.The study protocol has been approved by the Clinical Research Ethics Committees of Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital & Chongqing Cancer Center (2017[107]). The results from this trial will be submitted for publication in peer-reviewed journals, and will be presented at national and international conferences.


Subject(s)
Ascorbic Acid/administration & dosage , Castor Oil/administration & dosage , Cathartics/administration & dosage , Colonoscopy/methods , Polyethylene Glycols/administration & dosage , Adolescent , Adult , Aged , Dose-Response Relationship, Drug , Double-Blind Method , Drug Combinations , Female , Humans , Male , Middle Aged , Prospective Studies , Research Design , Young Adult
9.
Drug Deliv Transl Res ; 8(3): 515-524, 2018 06.
Article in English | MEDLINE | ID: mdl-29516407

ABSTRACT

Bupivacaine HCl (1-butyl-2',6'-pipecoloxylidide hydrochloride), an amide local anesthetic compound, is a local anesthetic drug utilized for intraoperative local anesthesia, post-operative analgesia and in the treatment of chronic pain. However, its utility is limited by the relative short duration of analgesia after local administration (approximately 9 h after direct injection) and risk for side effects. This work is aimed to develop a nanoemulsion of bupivacaine HCl with sustained local anesthetics release kinetics for improved pain management, by exhibiting extended analgesic action and providing reduced peak levels in the circulation to minimize side effects. Herein, biodegradable oils were evaluated for use in nanoemulsions to enable sustained release kinetics of bupivacaine HCl. Only with castor oil, a clear and stable nanoemulsion was obtained without the occurrence of phase separation over a period of 3 months. High loading of bupivacaine HCl into the castor oil-based nanoemulsion system was achieved with about 98% entrapment efficiency and the resulting formulation showed high stability under stress conditions (accelerated stability test) regarding changes in visual appearance, drug content, and droplet size. We show herein that the in vitro release and in vivo pharmacokinetic profiles as well as pharmacodynamic outcome (pain relief test) after subcutaneous administration in rats correlate well and clearly demonstrate the prolonged release and extended duration of activity of our novel nanoformulation. In addition, the lower Cmax value achieved in the blood compartment suggests the possibility that the risk for systemic side effects is reduced. We conclude that castor oil-based nanomulsion represents an attractive pain treatment possibility to achieve prolonged local action of bupivacaine HCl.


Subject(s)
Anesthetics, Local/administration & dosage , Bupivacaine/administration & dosage , Castor Oil/administration & dosage , Nanostructures/administration & dosage , Anesthetics, Local/chemistry , Anesthetics, Local/pharmacokinetics , Anesthetics, Local/therapeutic use , Animals , Bupivacaine/chemistry , Bupivacaine/pharmacokinetics , Bupivacaine/therapeutic use , Castor Oil/chemistry , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacokinetics , Delayed-Action Preparations/therapeutic use , Drug Liberation , Drug Stability , Electric Stimulation/adverse effects , Emulsions , Male , Nanostructures/chemistry , Nanostructures/therapeutic use , Pain/drug therapy , Rats, Wistar , Rheology , Viscosity
10.
Article in English | MEDLINE | ID: mdl-28745837

ABSTRACT

BACKGROUND: Irritable bowel syndrome (IBS) is characterized by abdominal pain, bloating, and changes in bowel habit. The aim of this study was to characterize the effect of loperamide hydrochloride (LOP) and naloxone hydrochloride (NLX), an opioid agonist and antagonist, respectively, on electrolyte equilibrium in ileal and colonic mucosae and to estimate the possible influence of divergent activity of the endogenous opioid system (EOS) on IBS therapy. METHODS: Two mouse lines bidirectionally selected for high (HA) and low (LA) swim stress-induced analgesia associated with high and low EOS activity were used in this study. To assess the effect of LOP and NLX on HA/LA lines in vivo, we used the castor oil-induced diarrhea model. Changes in electrolyte equilibrium were determined on the basis of short-circuit current (ΔIsc ) in isolated mouse ileum and colon exposed to LOP and NLX and stimulated by forskolin (FSK), veratridine (VER), and bethanechol (BET). KEY RESULTS: In vivo, we found that LOP significantly prolonged time to appearance of diarrhea in HA and LA lines. In vitro, LOP and NLX increased ΔIsc in FSK- and VER-stimulated colonic tissue, respectively, in HA line. In the ileum, LOP increased ΔIsc in FSK- and VER-stimulated tissue and decreased ΔIsc in BET-stimulated tissues in HA line. CONCLUSIONS & INFERENCES: Individual differences in EOS activity may play a crucial role in the response to the IBS-D therapy, thus some patients may be at an increased risk of side effects such as constipation or diarrhea.


Subject(s)
Analgesics, Opioid/administration & dosage , Colon/metabolism , Ileum/metabolism , Intestinal Mucosa/metabolism , Loperamide/administration & dosage , Stress, Psychological/metabolism , Animals , Castor Oil/administration & dosage , Colon/drug effects , Diarrhea/chemically induced , Ileum/drug effects , Intestinal Mucosa/drug effects , Male , Mice , Naloxone , Narcotic Antagonists/administration & dosage
11.
Women Birth ; 31(2): e99-e104, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28838804

ABSTRACT

AIM: To describe birthing outcomes among women who consumed castor oil cocktail as part of a freestanding birth center labor induction protocol. METHODS: De-identified data from birth logs and electronic medical records were entered into SPSS Statistics 22.0 for analysis for all women who received the castor oil cocktail (n=323) to induce labor between January 2008 and May 2015 at a birth center in the United States. Descriptive statistics were analyzed for trends in safety and birthing outcomes. RESULTS: Of the women who utilized the castor oil cocktail to stimulate labor, 293 (90.7%) birthed vaginally at the birth center or hospital. The incidence of maternal adverse effects (e.g., nausea, vomiting, extreme diarrhea) was less than 7%, and adverse effects of any kind were reported in less than 15% of births. An independent sample t-test revealed that parous women were more likely to birth vaginally at the birth center after using the castor oil cocktail than their nulliparous counterparts (p<.010), while gestational age (p=.26), woman's age (p=.23), and body mass index (p=.28) were not significantly associated. CONCLUSIONS: Nearly 91% of women in the study who consumed the castor oil cocktail to induce labor were able to give birth vaginally with little to no maternal or fetal complications. Findings indicate further research is needed to compare the safety and effectiveness of natural labor induction methodologies, including castor oil, to commonly used labor induction techniques in a prospective study or clinical trial.


Subject(s)
Castor Oil/administration & dosage , Labor Onset/drug effects , Labor, Induced/methods , Labor, Obstetric/drug effects , Administration, Oral , Adult , Birthing Centers , Castor Oil/pharmacology , Female , Gestational Age , Humans , Pregnancy , Pregnancy Outcome , Prenatal Care , Prospective Studies , Retrospective Studies , United States
12.
J Vet Pharmacol Ther ; 41(2): 307-313, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29139136

ABSTRACT

The combined antibacterial effects of tilmicosin (TIL) and florfenicol (FF) against Actinobacillus pleuropneumoniae (APP) (n = 2), Streptococcus suis (S. suis) (n = 2), and Haemophilus parasuis (HPS) (n = 2) were evaluated by chekerboard test and time-kill assays. The pharmacokinetics (PKs) of TIL- and FF-loaded hydrogenated castor oil (HCO)-solid lipid nanoparticles (SLN) were performed in healthy pigs. The results indicated that TIL and FF showed synergistic or additive antibacterial activities against APP, S. suis and HPS with the fractional inhibitory concentration (FIC) ranging from 0.375 to 0.75. The time-kill assays showed that 1/2 minimum inhibitory concentration (MIC) TIL combined with 1/2 MIC FF had a stronger ability to inhibit the growth of APP, S. suis, and HPS than 1 MIC TIL or 1 MIC FF, respectively. After oral administration, plasma TIL and FF concentrations could maintain about 0.1 µg/ml for 192 and 176 hr. The SLN prolonged the last time point with detectable concentrations (Tlast ), area under the concentration-time curve (AUC0-t ), elimination half-life (T½ke ), and mean residence time (MRT) by 3.1, 5.6, 12.7, 3.4-fold of the active pharmaceutical ingredient (API) of TIL and 11.8, 16.5, 18.1, 12.1-fold of the API of FF, respectively. This study suggests that the TIL-FF-SLN could be a useful oral formulation for the treatment of APP, S. suis, and HPS infection in pigs.


Subject(s)
Anti-Bacterial Agents/pharmacology , Swine Diseases/drug therapy , Thiamphenicol/analogs & derivatives , Tylosin/analogs & derivatives , Actinobacillus pleuropneumoniae/drug effects , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Castor Oil/administration & dosage , Drug Combinations , Drug Synergism , Haemophilus parasuis/drug effects , Hydrogenation , Male , Microbial Sensitivity Tests , Nanoparticles/administration & dosage , Streptococcus suis/drug effects , Swine , Swine Diseases/microbiology , Thiamphenicol/administration & dosage , Thiamphenicol/pharmacokinetics , Thiamphenicol/pharmacology , Tylosin/administration & dosage , Tylosin/pharmacokinetics , Tylosin/pharmacology
13.
Drug Deliv Transl Res ; 8(2): 375-386, 2018 04.
Article in English | MEDLINE | ID: mdl-28462499

ABSTRACT

Lipid-based drug delivery systems, a well-tolerated class of formulations, have been evaluated extensively to enhance the bioavailability of poorly soluble drugs. However, it has been difficult to predict the in vivo performance of lipid dosage forms based on conventional in vitro techniques such as cell monolayer permeability studies because of the complexity of the gastrointestinal processing of lipid formulations. In the current study, we explored the feasibility of coupling Caco-2 and Madin-Darby canine kidney monolayer permeability studies with lipolysis, a promising in vitro technique to evaluate lipid systems. A self-emulsifying lipid delivery system was formulated using a blend of oil (castor oil), surfactant (Labrasol® or PL497), and co-surfactant (lecithin). Formulations demonstrating high drug solubility and rapid self-emulsification were selected to study the effect of lipolysis on in vitro cell permeability. Lipolysis of the formulations was carried out using pancreatin as the digestive enzyme. All the digested formulations compromised monolayer integrity as indicated by lowered trans-epithelial electrical resistance (TEER) and enhanced Lucifer yellow (LY) permeability. Further, the changes in TEER value and LY permeability were attributable to the digestion products of the formulation rather than the individual lipid excipients, drug, digestion enzyme, or the digestion buffer. The digested formulations were fractionated into pellet, oily phase, and aqueous phase, and the effect of each of these on cell viability was examined. Interestingly, the aqueous phase, which is considered important for in vivo drug absorption, was responsible for cytotoxicity. Because lipid digestion products lead to disruption of cell monolayer, it may not be appropriate to combine lipolysis with cell monolayer permeability studies. Additional in vivo studies are needed to determine any potential side effects of the lipolysis products on the intestinal permeability barrier, which could determine the suitability of lipid-based systems for oral drug delivery.


Subject(s)
Drug Delivery Systems , Acridines/administration & dosage , Acridines/chemistry , Administration, Oral , Animals , Caco-2 Cells , Castor Oil/administration & dosage , Castor Oil/chemistry , Cell Survival/drug effects , Dogs , Excipients/administration & dosage , Excipients/chemistry , Humans , Lecithins/administration & dosage , Lecithins/chemistry , Lipolysis , Madin Darby Canine Kidney Cells , Permeability , Surface-Active Agents/administration & dosage , Surface-Active Agents/chemistry , Tetrahydroisoquinolines/administration & dosage , Tetrahydroisoquinolines/chemistry
14.
Women Birth ; 31(1): e26-e31, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28750937

ABSTRACT

BACKGROUND: Castor oil is a substance used for labor induction in an inpatient setting. However, its efficacy as an agent for the induction of labor, for post-date pregnancies in an outpatient setup is unknown. OBJECTIVE: Efficacy of castor oil as an agent for the induction of labor, for post-date pregnancies in outpatient settings. METHODS: Eighty-one women with a low-risk post-date singleton pregnancy with a Bishop score≤7, without effective uterine contractions were randomized to the intervention, 60ml of castor oil, or the control, 60ml of sun-flower oil. The primary outcome was proportion of women entering the active phase of labor 24, 36, 48h after ingestion. Secondary outcomes included meconium stained amniotic fluid, abnormal fetal heart rate tracing, cesarean section rate, instrumental deliveries, birth weight, 5min Apgar score, chorioamnionitis, hypertensive complications, retained placenta, and post-partum hemorrhage. FINDINGS: Intervention and control groups included 38 and 43 women, respectively. No differences in baseline characteristics, except for age were noted. The observed interaction between castor oil and parity was significant (pinteraction=0.02). Multiparous women in the intervention group exhibited a significant beneficial effect on entering active labor within 24, 36 and 48h after castor oil consumption compared with the placebo (Hazard Ratio=2.93, p=0.048; Hazard Ratio=3.29, p=0.026; Hazard Ratio=2.78, p=0.042 respectively). This effect was not noted among primiparous women. No differences in rate of obstetric complications or adverse neonatal outcomes were noted. CONCLUSION: Castor oil is effective for labor induction, in post-date multiparous women in outpatient settings.


Subject(s)
Castor Oil/administration & dosage , Delivery, Obstetric/methods , Labor Onset/drug effects , Labor, Induced/methods , Pregnancy, Prolonged/drug therapy , Sunflower Oil/administration & dosage , Administration, Oral , Adult , Female , Humans , Infant, Newborn , Pregnancy , Pregnancy Outcome , Pregnancy Trimester, Third
15.
J Dairy Sci ; 100(10): 8018-8032, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28803011

ABSTRACT

Dairy goats were fed a total mixed ration with or without the inclusion of castor oil [40 g/kg of dry matter (DM)] to study the metabolism of ricinoleic acid (12-OH,cis-9-18:1). Ten goats, at 39.7 ± 4.0 d in milk, were individually penned and allocated at random to the 2 experimental diets. Goats were manually milked twice a day. Milk fatty acids (FA) were analyzed as methyl esters and hydroxyl groups were derivatized in trimethylsilyl ethers. Apart from ricinoleic acid, 6 FA were only detected in the milk of the castor oil group. Ricinoleic acid composed 0.3% of total FA in milk of the castor oil group, whereas the hydroxy-FA (8-OH-14:0, 10-OH-16:0, and 12-OH-18:0) and oxo-FA (8-oxo-14:0, 10-oxo-16:0, and 12-oxo-18:0) reached 7.5% of total FA in milk. We anticipate that these FA were derived from the metabolism of ricinoleic acid, although it was not clear if they were produced in the rumen or in the tissues. To confirm that, we conducted in vitro batch incubations repeated for 3 consecutive weeks with castor oil (40 g/kg of DM) and strained rumen fluid from 2 fistulated sheep. To examine the products formed over time, incubation tubes were stopped at 0, 6, 12, 24, 48, and 72 h. The results of the in vitro experiment showed that ricinoleic acid was metabolized in the rumen at a slow rate and the main products formed were 12-OH-18:0 and 12-oxo-18:0, by hydrogenation of the cis-9 double bond, followed by oxidation of the hydroxyl group, respectively. Our results suggest that the 12-OH-18:0 and 12-oxo-18:0 escape rumen and are further metabolized through partial ß-oxidation in ruminant tissues. We propose that the 10-OH-16:0 and 8-OH-14:0 found in goat milk of the castor oil group are successive products of the ß-oxidation of 12-OH-18:0, and the 10-oxo-16:0 and 8-oxo-14:0 are successive products of the 12-oxo-18:0 in tissues. Overall, our results indicate that ricinoleic acid is extensively metabolized in the rumen and tissues, producing mainly oxo- and hydroxy-FA that are further excreted in milk.


Subject(s)
Fatty Acids/metabolism , Milk/chemistry , Ricinoleic Acids/metabolism , Animals , Castor Oil/administration & dosage , Diet , Fatty Acids/analysis , Female , Goats , Lactation , Milk/metabolism , Random Allocation , Ricinoleic Acids/analysis , Rumen
16.
Biomed Pharmacother ; 94: 787-793, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28802231

ABSTRACT

INTRODUCTION: Several research studies have reported on the pharmacological relevance of the medicinal plants used for treating various gastrointestinal disorders and controlling the dietary glucose uptake in the intestinal tract. METHODS: Male rats were used to investigate the pharmacological effects of green oak acorn aqueous extract (GOAE) on gastrointestinal physiological parameters in vivo and in vitro. In this respect, the gastro-intestinal motility and hypersecretion essays were evaluated using a simple test meal (10% charcoal in 5% gum arabic) and castor oil induced diarrhea. However, the effect of GOAE on glucose absorption and homeostasis was assessed by the Ussing chamber system and oral glucose tolerance test (OGTT) measures. RESULTS: Various doses of the Quercus ilex aqueous extract (125, 250 and 500mgkg-1) administered orally produced a significantly dose-related inhibition of gut meal travel distance in normal rat. The highest intestinal transit reduction of 49.34% was obtained with 500mgkg-1 compared to 58.33% caused by reference drug (clonidine, 1mgkg-1). In castor oil induced diarrhea in rat, Q. ilex extract reduced the frequency of defecation, fluid accumulation and electrolyte transport. These effects were associated with decreased histopathological damage and regulation of intracellular mediators disturbance in the intestinal mucosa. In addition, GOAE treatment improved glucose tolerance and significantly and dose-dependently reduced (>50%) the glucose absorption via intestinal epithelium. Phytochemical screening revealed the presence of many bioactive natural compounds. CONCLUSION: These results suggest that the extract was effective towards reducing diarrhea, fluid accumulation, electrolyte transport and glucose absorption, and no toxic effects of the GOAE presented on this study.


Subject(s)
Antidiarrheals/pharmacology , Diarrhea/drug therapy , Plant Extracts/pharmacology , Quercus/chemistry , Animals , Antidiarrheals/administration & dosage , Biological Transport/drug effects , Castor Oil/administration & dosage , Clonidine/pharmacology , Dose-Response Relationship, Drug , Electrolytes/metabolism , Gastrointestinal Motility/drug effects , Glucose/metabolism , Glucose Tolerance Test , Male , Mice , Plant Extracts/administration & dosage , Rats , Rats, Wistar
17.
J Vet Pharmacol Ther ; 40(3): 293-303, 2017 Jun.
Article in English | MEDLINE | ID: mdl-27687707

ABSTRACT

To effectively control bovine mastitis, tilmicosin (TIL)- and florfenicol (FF)-loaded solid lipid nanoparticles (SLN) with hydrogenated castor oil (HCO) were prepared by a hot homogenization and ultrasonication method. In vitro antibacterial activity, properties, and pharmacokinetics of the TIL-FF-SLN were studied. The results demonstrated that TIL and FF had a synergistic or additive antibacterial activity against Streptococcus dysgalactiae, Streptococcus uberis, and Streptococcus agalactiae. The size, polydispersity index, and zeta potential of nanoparticles were 289.1 ± 13.7 nm, 0.31 ± 0.05, and -26.7 ± 1.3 mV, respectively. The encapsulation efficiencies for TIL and FF were 62.3 ± 5.9% and 85.1 ± 5.2%, and the loading capacities for TIL and FF were 8.2 ± 0.6% and 3.3 ± 0.2%, respectively. The TIL-FF-SLN showed no irritation in the injection site and sustained release in vitro. After medication, TIL and FF could maintain about 0.1 µg/mL for 122 and 6 h. Compared to the control solution, the SLN increased the area under the concentration-time curve (AUC0-t ), elimination half-life (T½ke ), and mean residence time (MRT) of TIL by 33.09-, 23.29-, and 37.53-fold, and 1.69-, 5.00-, and 3.83-fold for FF, respectively. These results of this exploratory study suggest that the HCO-SLN could be a useful system for the delivery of TIL and FF for bovine mastitis therapy.


Subject(s)
Mastitis, Bovine/drug therapy , Thiamphenicol/analogs & derivatives , Tylosin/analogs & derivatives , Animals , Anti-Bacterial Agents , Castor Oil/administration & dosage , Cattle , Chemistry, Pharmaceutical , Drug Synergism , Female , Lipids/administration & dosage , Nanoparticles , Particle Size , Thiamphenicol/pharmacokinetics , Tylosin/pharmacokinetics
18.
J Vet Med Sci ; 76(9): 1219-24, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24881653

ABSTRACT

The corneal-protective effects of an artificial tear containing sodium hyaluronate (SH) and castor oil (CO) were evaluated on a porcine short-term dry eye model. Fresh porcine eyes with an intact cornea were treated with an artificial tear of saline, SH solution (0.1%, 0.5% or 1%), CO solution (0.5%, 1% or 5%) or a mixture solution containing 0.5% SH and 1% CO and then desiccated for 60, 90 or 180 min. To assess corneal damage, the eyes were stained with methylene blue (MB) or lissamine green (LG). The staining score of MB, absorbance of MB extracted from the cornea and staining density of LG increased significantly with increasing desiccation time in untreated and all artificial tear-treated eyes, although there were no significant differences in staining scores and absorbance of MB between eyes treated continuously with saline and 1% SH-treated ones at 60 and 90 min of desiccation or the mixture-treated eyes at 60 min of desiccation. No significant differences in the staining density of LG were also found between continuous saline-treated eyes and ones desiccated for 60 min and treated with 1% SH and the mixture. Mild cytoplasmic vacuolations were histopathologically observed in the basal and wing cells in eyes desiccated for 60 min and treated with 1% SH and the mixture. The mixture solution containing 0.5% SH and 1% CO has protective effects against corneal desiccation similar to those of 1% SH and would be helpful as an artificial tear.


Subject(s)
Castor Oil/pharmacology , Cornea/drug effects , Dry Eye Syndromes/drug therapy , Hyaluronic Acid/pharmacology , Lubricant Eye Drops/pharmacology , Animals , Castor Oil/administration & dosage , Castor Oil/therapeutic use , Histocytochemistry/veterinary , Hyaluronic Acid/administration & dosage , Hyaluronic Acid/therapeutic use , In Vitro Techniques/veterinary , Lubricant Eye Drops/administration & dosage , Lubricant Eye Drops/therapeutic use , Statistics, Nonparametric , Swine
19.
Curr Opin Obstet Gynecol ; 25(6): 441-7, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24121598

ABSTRACT

PURPOSE OF REVIEW: The percentage of induced live birth has more than doubled from the 1990s to 2008. Induction of labour can either be based on medical indications, or performed as an elective procedure. A large range of pharmacological and non-pharmacological modalities are available for the induction of labour and the optimal method for labour induction is unknown. This article is aimed to examine literature on non-hormonal methods for labour induction, published from January 2012 to May 2013. RECENT FINDINGS: Eleven studies were identified in our search and included into the review. Foley balloon catheter appears to be more cost-effective and commonly used non-hormonal technique for induction of labour, although further meta-analysis is required in this area. Currently, there is not enough evidence to support routine use in all women for labour induction among other methods including amniotomy, acupuncture, sexual intercourse, isosorbide mononitrate, hypnosis, castor oil and breast stimulation. The latest three studies suggest that amniotomy may increase need for oxytocin augmentation during labour induction. SUMMARY: Many non-hormonal methods for labour induction still require further evidence to support their use within the clinical setting. Balloon catheter seems to be a more widely accepted non-hormonal method that has been supported by various literatures.


Subject(s)
Cervical Ripening/physiology , Labor, Induced/methods , Acupuncture Therapy/methods , Amnion/surgery , Breast/physiology , Castor Oil/administration & dosage , Catheterization/methods , Coitus/physiology , Female , Humans , Isosorbide Dinitrate/analogs & derivatives , Isosorbide Dinitrate/therapeutic use , Oxytocics/administration & dosage , Oxytocin/administration & dosage , Pregnancy , Treatment Outcome , Vasodilator Agents/administration & dosage
20.
Cochrane Database Syst Rev ; (7): CD003099, 2013 Jul 24.
Article in English | MEDLINE | ID: mdl-23881775

ABSTRACT

BACKGROUND: Castor oil, a potent cathartic, is derived from the bean of the castor plant. Anecdotal reports, which date back to ancient Egypt have suggested the use of castor oil to stimulate labour. Castor oil has been widely used as a traditional method of initiating labour in midwifery practice. Its role in the initiation of labour is poorly understood and data examining its efficacy within a clinical trial are limited. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. OBJECTIVES: To determine the effects of castor oil or enemas for third trimester cervical ripening or induction of labour in comparison with other methods of cervical ripening or induction of labour. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013) and bibliographies of relevant papers. SELECTION CRITERIA: Clinical trials comparing castor oil, bath or enemas used for third trimester cervical ripening or labour induction with placebo/no treatment or other methods listed above it on a predefined list of labour induction methods. DATA COLLECTION AND ANALYSIS: A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two-stage method of data extraction. MAIN RESULTS: Three trials, involving 233 women, are included. There was no evidence of differences in caesarean section rates between the two interventions in the two trials reporting this outcome (risk ratio (RR) 2.04, 95% confidence interval (CI) 0.92 to 4.55). There were no data presented on neonatal or maternal mortality or morbidity.There was no evidence of a difference between castor oil and placebo/no treatment for the rate of instrumental delivery, meconium-stained liquor, or Apgar score less than seven at five minutes. The number of participants was too small to detect all but large differences in outcome. All women who ingested castor oil felt nauseous (RR 59.92, 95% CI 8.46 to 424.52). AUTHORS' CONCLUSIONS: The three trials included in the review contain small numbers of women. All three studies used single doses of castor oil. The results from these studies should be interpreted with caution due to the risk of bias introduced due to poor methodological quality. Further research is needed to attempt to quantify the efficacy of castor oil as an cervical priming and induction agent.


Subject(s)
Castor Oil , Cervical Ripening , Enema , Labor, Induced/methods , Oxytocics , Castor Oil/administration & dosage , Castor Oil/adverse effects , Cesarean Section/statistics & numerical data , Female , Humans , Oxytocics/administration & dosage , Oxytocics/adverse effects , Pregnancy , Pregnancy Trimester, Third , Prostaglandins , Randomized Controlled Trials as Topic
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