Predicting in vivo absorption of chloramphenicol in frogs using in vitro percutaneous absorption data.

BACKGROUND: Infectious disease, particularly the fungal disease chytridiomycosis (caused by Batrachochytrium dendrobatidis), is a primary cause of amphibian declines and extinctions worldwide. The transdermal route, although offering a simple option for drug administration in frogs, is complicated by the lack of knowledge regarding percutaneous absorption kinetics. This study builds on our previous studies in frogs, to formulate and predict the percutaneous absorption of a drug for the treatment of infectious disease in frogs. Chloramphenicol, a drug with reported efficacy in the treatment of infectious disease including Batrachochytrium dendrobatidis, was formulated with 20% v/v propylene glycol and applied to the ventral pelvis of Rhinella marina for up to 6 h. Serum samples were taken during and up to 18 h following exposure, quantified for chloramphenicol content, and pharmacokinetic parameters were estimated using non-compartmental analysis. RESULTS: Serum levels of chloramphenicol reached the minimum inhibitory concentration (MIC; 12.5 µg.mL- 1) for Batrachochytrium dendrobatidis within 90-120 min of exposure commencing, and remained above the MIC for the remaining exposure time. Cmax (17.09 ± 2.81 µg.mL- 1) was reached at 2 h, while elimination was long (t1/2 = 18.68 h). CONCLUSIONS: The model, based on in vitro data and adjusted for formulation components and in vivo data, was effective in predicting chloramphenicol flux to ensure the MIC for Batrachochytrium dendrobatidis was reached, with serum levels being well above the MICs for other common bacterial pathogens in frogs. Chloramphenicol's extended elimination means that a 6-h bath may be adequate to maintain serum levels for up to 24 h. We suggest trialling a reduction of the currently-recommended continuous (23 h/day for 21-35 days) chloramphenicol bathing for chytrid infection with this formulation.

Agar/κ-carrageenan/montmorillonite nanocomposite hydrogels for wound dressing applications.

In this study, agar/κ-carrageenan/montmorillonite (MMT) hydrogels were prepared to examine their usability as wound dressing materials and to see the effect of MMT amount on some properties of agar/κ-carrageenan hydrogel materials. Hydrogels were characterized by SEM-EDX, TEM and DSC analyses. By increasing the MMT content within hydrogel matrix from 0% to 5%, the decomposition temperature of the hydrogel material was increased from 256.6 °C to 262.1 °C. Swelling amount of hydrogels in d-glucose solution (2682%) was found to be much higher compared with other physiological solutions such as physiological saline solution (937%), synthetic urine solution (746%) and simulated wound fluid (563%). The release studies of analgesic lidocaine hydrochloride (LDC) and antibiotic chloramphenicol (CLP) drugs from hydrogel systems demonstrated that the release amount of LDC and CLP from hydrogels could be controlled by MMT amount within hydrogel matrix. The concentrations of drugs within hydrogel sample stored at 4 °C for 6 months did not exhibit a significant change. Hydrogel materials containing CLP exhibited good antibacterial activity against E. coli and S. aureus. Cytotoxicity test results indicated that hydrogels were biocompatible with MG-63 cells. The ultimate compressive stress of agar/κ-carrageenan hydrogel with LDC and CLP and agar/κ-carrageenan/MMT hydrogel including 5% MMT with LDC and CLP was measured as 38.30 kPa and 47.70 kPa, respectively. The experimental results revealed that prepared agar/κ-carrageenan and agar/κ-carrageenan/MMT hydrogels have great potential for wound care applications.

Pharmacokinetics of multiple doses of chloramphenicol in fed adult horses.

To the authors' knowledge, there have been no studies evaluating the pharmacokinetics of chloramphenicol administered orally to horses at the currently recommended dose of 50 mg/kg PO q6 h for multiple days. The published antimicrobial susceptibility breakpoint is 8.0 ug/mL; it is unknown if this concentration is achievable at the recommended dose rate in horses. The aim of this prospective multi-dose pharmacokinetic study was to perform pharmacokinetic analysis of chloramphenicol after multiple doses. The authors hypothesize that the antimicrobial susceptibility breakpoint will not be reached. Seven healthy adult horses were administered 50 mg/kg chloramphenicol base tablets PO q6 h for 4 days. Blood was collected via venipuncture daily at 4 and 6 h after administration for the first 15 doses. After the 16th dose, an IV catheter was aseptically placed in the right jugular vein and blood was collected at regular intervals for pharmacokinetic analysis. Maximum chloramphenicol concentration was variable between horses (2.1-42.7 µg/mL). The highest average chloramphenicol concentration was just below the susceptibility breakpoint at 7.7 ug/mL while the lowest was well below the breakpoint at 1.5 ug/mL. On average, the time above 8.0 µg/mL was 75 min, considerably less than the recommended 50% of the dosing interval. When chloramphenicol is administered at a dose of 50 mg/kg PO q6 h in horses, the highest reliably achievable steady state concentration for at least half of the dosing interval is 2.0 µg/mL. The established susceptibility breakpoint of 8.0 ug/mL is not achievable in adult horses, and should be re-evaluated.

Pharmacokinetics of anti-infectious reagents in silkworms.

Silkworm microorganism infection models are useful for screening novel therapeutically effective antimicrobial agents. In this study, we used silkworms to investigate the pharmacokinetics and metabolism of antimicrobial agents, in which cytochrome P450 plays a major role. The pharmacokinetic parameters of the antimicrobial agents were determined based on their concentrations in the hemolymph after administration. The parameters, such as half-lives and distribution volumes, in silkworm were consistent with those in mammalian models. In addition, antifungal agents with reduced therapeutic effectiveness due to high protein-binding capacities in mammalian serum exhibited similar features in silkworm hemolymph. Cytochrome P450 enzymes, which metabolize exogenous compounds in mammalian liver, were distributed mainly in the silkworm midgut. Most of the compounds metabolized by cytochrome P450 in humans are also metabolized in the silkworm midgut. These findings suggest that the pharmacokinetics of antimicrobial agents are fundamentally similar between silkworms and mammals, and that therapeutic effects in the silkworm infection model reflect the pharmacokinetics of the test samples.

Pharmacokinetics of chloramphenicol base in horses and comparison to compounded formulations.

Chloramphenicol is commonly used in horses; however, there are no studies evaluating the pharmacokinetics of veterinary canine-approved tablets. Studies using different formulations and earlier analytical techniques led to concerns over low bioavailability in horses. Safety concerns about human health have led many veterinarians to prescribe compounded formulations that are already in suspension or paste form. The objective of this study was to evaluate the pharmacokinetics of approved chloramphenicol tablets in horses, along with compounded preparations. The hypothesis was that chloramphenicol has low absorption and a short half-life in horses leading to low serum concentrations and that compounded preparations have lower relative bioavailability. Seven horses were administered chloramphenicol tablets (50 mg/kg orally). In a crossover design, they were administered two compounded preparations to compare all three formulations at the same dose (50 mg/kg). Cmax was 5.25 ± 4.07 µg/ml at 4.89 hr, 4.96 ± 3.31 µg/ml at 4.14 hr, and 3.84 ± 2.96 µg/ml at 4.39 hr for the tablets, paste, and suspension, respectively. Elimination half-life was 2.65 ± 0.75, 3.47 ± 1.47, and 4.36 ± 4.54 hr for tablets, paste, and suspension, respectively. The AUC0→∞ was 17.93 ± 7.69, 16.25 ± 1.85, and 14.00 ± 5.47 hr*µg/ml for the tablets, compounded paste, and compounded suspension, respectively. Relative bioavailability of compounded suspension and paste was 78.1% and 90.6%. Cmax after administration of all formulations did not reach the recommended MIC target of 8 µg/ml set by the Clinical Laboratory Standards Institute (CLSI) for most bacteria. Multidose studies are warranted, but the low serum concentrations suggest that bacteria with MIC values lower than CLSI recommendations should be targeted in adult horses.

Mycobacterium tuberculosis Rv0191 is an efflux pump of major facilitator superfamily transporter regulated by Rv1353c.

Development of extensively drug resistant (XDR) strains and multidrug resistant (MDR) in Mycobacterium tuberculosis is caused by an efflux mechanism of antibiotics in the bacteria. Rv0191, predicted to a major facilitator superfamily transporter of efflux pump, contributes to elevated expression in some clinical isolates. To characterize the role of Rv0191 which might be involved in antibiotics resistance, Mycobacterium smegmatis was taken as a type strains to do drug susceptibility, ethidium bromide (EB) accumulation assay and electrophoretic mobility shift assay. M. smegmatis Ms0232 mutant became more susceptible to chloramphenicol and showed different cell surface properties. Rv1353c, a TetR family transcription factor, can downregulate the transcription of Rv0191. Rv1353c overexpression strain became more sensitive to chloramphenicol. Together, these findings indicate that Rv1353c encodes a transcriptional repressor that directly interacts with the Rv0191 promoter and modulates the expression of Rv0191. This provided a new player in mycobacteria chloramphenicol resistance.

Chloramphenicol/sulfobutyl ether-ß-cyclodextrin complexes in an ophthalmic delivery system: prolonged residence time and enhanced bioavailability in the conjunctival sac.

Objective: Conventional chloramphenicol (CHL) eye drops are widely used anti-infection formulations for acute bacterial conjunctivitis. However, the therapeutic effects are limited by insufficient concentration in the conjunctival sac. Hence, the objective of this study is to formulate and develop novel CHL eye drops with improved topical concentrations by increasing the solubility and decreasing the transcorneal penetration. Research design and methods: CHL was included in the sulfobutyl ether-ß-cyclodextrin (SBE-ß-CD) using the freeze-drying method. Eye drops containing CHL/SBE-ß-CD complexes were prepared and evaluated for in vitro and in vivo studies. Results: The formation of CHL/SBE-ß-CD inclusion was confirmed by DSC, XRD, NMR, and SEM. The aqueous solubility of CHL was significantly enhanced, and the drug transcorneal penetration was inhibited after inclusion. The CHL/SBE-ß-CD displayed sustained release profiles. The tear fluid elimination kinetic study showed that the CHL/SBE-ß-CD eye drops had better ability to prolong the residence time, and significantly increase CHL concentration in the conjunctival sac. Besides, it was shown that CHL/SBE-ß-CD eye drops were nonirritating to rabbits' eyes. Conclusions: The SBE-ß-CD inclusions offer a potential alternative strategy for ocular administration of poorly water-soluble drugs in the conjunctival sac.

Construction of a simple evaluation system for the intestinal absorption of an orally administered medicine using Bombyx mori larvae.

Human intestinal absorption is estimated using a human colon carcinoma cell line (Caco-2) cells from human colorectal adenocarcinoma, intestinal perfusion, or a mammalian model. These current evaluation systems are limited in their ability to estimate human intestinal absorption. In addition, in vivo evaluation systems using laboratory animals such as mice and rats entail animal ethics problems, and it is difficult to screen compounds on a large scale at the drug discovery stage. Thus, we propose the use of Bombyx mori larvae for evaluation of intestinal absorption of compounds as an alternative system in this study. First, to compare the characteristics among Caco-2 cells, human intestine, and B. mori larval midgut, we analyzed their RNA-seq data, and we found 26 drug transporters common to humans and B. mori. Next, we quantitatively developed an oral administration technique in B. mori and established a method using silkworm B. mori larvae that can easily estimate the intestinal permeability of compounds. Consequently, we could determine the dose and technique for oral administration in B. mori larvae. We also developed a B. mori model to evaluate the intestinal permeability of orally administered. Our constructed evaluation system will be useful for evaluating intestinal permeability in medical drug development.

Integrated Genomic and Proteomic Analyses of High-level Chloramphenicol Resistance in Campylobacter jejuni.

Campylobacter jejuni is a major zoonotic pathogen, and its resistance to antibiotics is of great concern for public health. However, few studies have investigated the global changes of the entire organism with respect to antibiotic resistance. Here, we provide mechanistic insights into high-level resistance to chloramphenicol in C. jejuni, using integrated genomic and proteomic analyses. We identified 27 single nucleotide polymorphisms (SNPs) as well as an efflux pump cmeB mutation that conferred modest resistance. We determined two radical S-adenosylmethionine (SAM) enzymes, one each from an SNP gene and a differentially expressed protein. Validation of major metabolic pathways demonstrated alterations in oxidative phosphorylation and ABC transporters, suggesting energy accumulation and increase in methionine import. Collectively, our data revealed a novel rRNA methylation mechanism by a radical SAM superfamily enzyme, indicating that two resistance mechanisms existed in Campylobacter. This work provided a systems biology perspective on understanding the antibiotic resistance mechanisms in bacteria.

Association of Permeability and Lipid Content of Membrane.

BACKGROUND: Rat skin and goat cul de sac are mostly used in optimization of formulations as the model of human skin and cul de sac. AIM: To explore the correlation between lipid content of rat skin and goat cul de sac and permeability. MATERIALS AND METHODS: Find out wavelength maximum for Sapat plus malam®, Ciplox eye ointment® and chloramphenicol eye caps and the standard curve was also derived. In vitro studies using Cellophane® membrane and ex vivo studies using rat skin or goat cul de sac of the formulations. Permeability coefficient, % dislodgeable dose, lag time, diffusion parameter, and partition coefficient were found for both studies after six and a half hours of penetration studies. Student's unpaired t-test with equal variance was used to find any statistically significant difference in the ex vivo and in vitro diffusion transport studies at 95% level of confidence. RESULTS: Permeability coefficient of Sapat plus malam®, Ciplox eye ointment® and chloramphenicol eye caps were 0.000316 ± 0.0000625, 0.00416 ± 0.0001, 0.0034 ± 0.00004 for Cellophane® membrane and 0.0001 ± 0.000001, 0.002254 ± 0.0002, 0.00303 ± 0.0001 for ex vivo membrane in cm2/min, respectively. For all three formulations, there were calculated t values which were higher than tabulated t values at 95% of confidence level (P<0.05). CONCLUSION: Cellophane® membrane shows a better diffusion than rat skin or goat cul de sac. In the optimization of formulation, only Cellophane® membrane is advisable to use.

Unusual acylation of chloramphenicol in Lysobacter enzymogenes, a biocontrol agent with intrinsic resistance to multiple antibiotics.

BACKGROUND: The environmental gliding bacteria Lysobacter are emerging as a new group of biocontrol agents due to their prolific production of lytic enzymes and potent antibiotic natural products. These bacteria are intrinsically resistant to many antibiotics, but the mechanisms behind the antibiotic resistance have not been investigated. RESULTS: Previously, we have used chloramphenicol acetyltransferase gene (cat) as a selection marker in genetic manipulation of natural product biosynthetic genes in Lysobacter, because chloramphenicol is one of the two common antibiotics that Lysobacter are susceptible to. Here, we found L. enzymogenes, the most studied species of this genus, could still grow in the presence of a low concentration of chloramphenicol. Three chloramphenicol derivatives (1-3) with an unusual acylation pattern were identified in a cat-containing mutant of L. enzymogenes and in the wild type. The compounds included chloramphenicol 3'-isobutyrate (1), a new compound chloramphenicol 1'-isobutyrate (2), and a rare chloramphenicol 3'-isovalerate (3). Furthermore, a mutation of a global regulator gene (clp) or a Gcn5-related N-acetyltransferase (GNAT) gene in L. enzymogenes led to nearly no growth in media containing chloramphenicol, whereas a complementation of clp restored the chloramphenicol acylation as well as antibiotic HSAF production in the clp mutant. CONCLUSIONS: The results indicated that L. enzymogenes contains a pool of unusual acyl donors for enzymatic modification of chloramphenicol that confers the resistance, which may involve the Clp-GNAT regulatory system. Because Lysobacter are ubiquitous inhabitants of soil and water, the finding may have important implications in understanding microbial competitions and bioactive natural product regulation.

Pharmacokinetics of chloramphenicol base after oral administration in adult horses.

OBJECTIVE To determine the pharmacokinetics of chloramphenicol base after PO administration at a dose of SO mg/kg (22.7 mg/lb) in adult horses from which food was not withheld. DESIGN Prospective crossover study. ANIMALS 5 adult mares. PROCEDURES Chloramphenicol base (SO mg/kg) was administered PO to each horse, and blood samples were collected prior to administration (0 minutes) and at 5, 10, 15, and 30 minutes and 1, 2, 4, 8, and 12 hours thereafter. Following a washout period, chloramphenicol sodium succinate (25 mg/kg [11.4 mg/lb]) was administered IV to each horse, and blood samples were collected prior to administration (0 minutes) and at 3, 5, 10, 15, 30, and 45 minutes and 1, 2, 4, and 8 hours thereafter. RESULTS In horses, plasma half-life, volume of distribution at steady state, clearance, and area under the plasma concentration-time curve for chloramphenicol after IV administration ranged from 0.65 to 1.20 hours, 0.51 to 0.78 L/kg, 0.78 to 1.22 L/h/kg, and 20.5 to 32.1 h·µg/mL, respectively. The elimination half-life, time to maximum plasma concentration, maximum plasma concentration, and area under the plasma concentration-time curve after PO administration ranged from 1.7 to 7.4 hours, 0.25 to 2.00 hours, 1.52 to 5.45 µg/mL, and 10.3 to 21.6 h·µg/mL, respectively. Mean ± SD chloramphenicol bioavailability was 28 ± 10% and terminal half-life was 2.85 ± 1.32 hours following PO administration. CONCLUSIONS AND CLINICAL RELEVANCE Given that the maximum plasma chloramphenicol concentration in this study was lower than previously reported values, it is recommended to determine the drug's MIC for target bacteria before administration of chloramphenicol in adult horses.

Emulsion of Chloramphenicol: an Overwhelming Approach for Ocular Delivery.

BACKGROUND: Ophthalmic formulations of chloramphenicol have poor bioavailability of chloramphenicol in the ocular cavity. AIM: The present study aimed at exploring the impact of different oil mixtures in the form of emulsion on the permeability of chloramphenicol after ocular application. MATERIALS AND METHODS: Selection of oil mixture and ratio of the components was made by an equilibrium solubility method. An emulsifier was chosen according to its emulsification properties. A constrained simplex centroid design was used for the assessment of the emulsion development. Emulsions were evaluated for physicochemical properties; zone of inhibition, in-vitro diffusion and ex-vivo local accumulation of chloramphenicol. Validation of the design using check-point batch and reduced polynomial equations were also developed. Optimization of the emulsion was developed by software Design® expert 6.0.8. Assessment of the osmolarity, ocular irritation, sterility testing and isotonicity of optimized batch were also made. RESULTS: Parker Neem®, olive and peppermint oils were selected as an oil phase in the ratio 63.64:20.2:16.16. PEG-400 was selected as an emulsifier according to a pseudo-ternary phase diagram. Constrained simplex-centroid design was applied in the range of 25-39% water, 55-69% PEG-400, 5-19% optimized oil mixture, and 1% chloramphenicol. Unpaired Student's t-test showed for in-vitro and ex-vivo studies that there was a significant difference between the optimized batch of emulsion and Chloramphenicol eye caps (a commercial product) according to both were equally safe. CONCLUSION: The optimized batch of an emulsion of chloramphenicol was found to be as safe as and more effective than Chloramphenicol eye caps.

Transfer of vaginal chloramphenicol to circulating blood in pregnant women and its relationship with their maternal background and neonatal health.

Few clinical studies have determined the quantitative transfer of vaginal chloramphenicol to circulating blood in pregnant women. This study aimed to evaluate the plasma concentration of chloramphenicol in pregnant women treated with trans-vaginal tablets and its relationship with maternal background and neonatal health. Thirty-seven pregnant women treated with 100 mg of trans-vaginal chloramphenicol once daily for bacterial vaginosis and its suspected case were enrolled. The plasma concentration of chloramphenicol was determined using liquid chromatography coupled to tandem mass spectrometry at day 2 or later after starting the medication. The correlations between the maternal plasma concentration of chloramphenicol and the background and neonatal health at birth were investigated. Chloramphenicol was detected from all maternal plasma specimens and its concentration ranged from 0.043 to 73.1 ng/mL. The plasma concentration of chloramphenicol declined significantly with the administration period. The plasma concentration of chloramphenicol was lower at the second than the first blood sampling. No correlations were observed between the maternal plasma concentration of chloramphenicol and background such as number of previous births, gestational age at dosing, and clinical laboratory data. Neonatal infant health parameters such as birth-weight, Apgar score at birth, and gestational age at the time of childbearing were not related to the maternal plasma concentration of chloramphenicol. Vaginal chloramphenicol transfers to circulating blood in pregnant women. The maternal plasma concentration of chloramphenicol varied markedly and was associated with the administration day, but not with maternal background or her neonatal health.

Distribution of chloramphenicol to tissues, plasma and urine in pigs after oral intake of low doses.

Toxic effects of chloramphenicol in humans caused the ban for its use in food-producing animals in the EU. A minimum required performance level (MRPL) was specified for chloramphenicol at 0.3 µg kg(-1) for various matrices, including urine. In 2012, residues of chloramphenicol were found in pig urine and muscle without signs of illegal use. Regarding its natural occurrence in straw, it was hypothesised that this might be the source, straw being compulsory for use as bedding material for pigs in Sweden. Therefore, we investigated if low daily doses of chloramphenicol (4, 40 and 400 µg/pig) given orally during 14 days could result in residues in pig tissues and urine. A dose-related increase of residues was found in muscle, plasma, kidney and urine (showing the highest levels), but no chloramphenicol was found in the liver. At the lowest dose, residues were below the MRPL in all tissues except in the urine. However, in the middle dose, residues were above the MRPL in all tissues except muscle, and at the highest dose in all matrices. This study proves that exposure of pigs to chloramphenicol in doses occurring naturally in straw could result in residues above the MRPL in plasma, kidney and especially urine.

Development of LC-MS/MS methodology for the detection/determination and confirmation of chloramphenicol, chloramphenicol 3-O-ß-d-glucuronide, florfenicol, florfenicol amine and thiamphenicol residues in bovine, equine and porcine liver.

A method for the detection and confirmation of organic solvent extractable residues of the neutral, acidic, and basic analytes of the amphenicol class veterinary drugs and selected metabolites was developed and validated. Using a modified QuEChERS extraction with SPE cleanup and LC-MS/MS analysis, limits of detection and confirmation for the different analytes in bovine, equine, and porcine liver ranged from 0.1ng/g for chloramphenicol to 1ng/g for florfenicol amine. Tissue homogenization with an ammonium formate/EDTA solution and subsequent analyte partitioning against 7:3 acetonitrile:isopropanol solution and mixed-mode strong-cation exchange solid-phase extraction cartridge cleanup allowed for the extraction of all compounds from tissues with mean recoveries ranging from 50% (chloramphenicol 3-O-ß-d-glucuronide) to 90% (thiamphenicol). Matrix effects ranged from greater than 85% suppression for florfenicol amine to 70% matrix enhancement for chloramphenicol 3-O-ß-d-glucuronide. Quantitation and confirmation were accomplished using commercially available penta-deuterated chloramphenicol as internal standard and multiple reaction monitoring (MRM) of two or three transitions per target analyte. Method accuracy was greater than 15% for all compounds except the glucuronide metabolite. Intra-lab method repeatability estimates ranged from 73% RSD for chloramphenicol 3-O-ß-d-glucuronide to 14% RSD for chloramphenicol. Only chloramphenicol 3-O-ß-d-glucuronide and florfenicol amine at the low end of their calibration ranges (0.25 and 1ng/g, respectively) did not meet AOAC recommended HorRatr guidelines for intra-lab repeatabilities. Preliminary tests show that the method's extraction protocol can be used to recover analytes of the ß-agonists, corticosteroids, fluoroquinolones, sulfonamides, and tetracycline drug classes from the same matrices. Requirements for use in national chemical monitoring programs as a detection/confirmatory (florfenicol amine and chloramphenicol 3-O-ß-d-glucuronide) and determinative/confirmatory (chloramphenicol, florfenicol, thiamphenicol) analytical methodology are met.

Effects of dissolved organic matter from a eutrophic lake on the freely dissolved concentrations of emerging organic contaminants.

The authors studied the effects of dissolved organic matter (DOM) on the bioavailability of bisphenol A (BPA) and chloramphenicol by measuring the freely dissolved concentrations of the contaminants in solutions containing DOM that had been isolated from a mesocosm in a eutrophic lake. The abundance and aromaticity of the chromophoric DOM increased over the 25-d mesocosm experiment. The BPA freely dissolved concentration was 72.3% lower and the chloramphenicol freely dissolved concentration was 56.2% lower using DOM collected on day 25 than using DOM collected on day 1 of the mesocosm experiment. The freely dissolved concentrations negatively correlated with the ultraviolent absorption coefficient at 254 nm and positively correlated with the spectral slope of chromophoric DOM, suggesting that the bioavailability of these emerging organic contaminants depends on the characteristics of the DOM present. The DOM-water partition coefficients (log KOC ) for the emerging organic contaminants positively correlated with the aromaticity of the DOM, measured as humic acid-like fluorescent components C1 (excitation/emission=250[313]/412 nm) and C2 (excitation/emission=268[379]/456 nm). The authors conclude that the bioavailability of emerging organic contaminants in eutrophic lakes can be affected by changes in the DOM.

Formulation optimization of palm kernel oil esters nanoemulsion-loaded with chloramphenicol suitable for meningitis treatment.

Palm kernel oil esters nanoemulsion-loaded with chloramphenicol was optimized using response surface methodology (RSM), a multivariate statistical technique. Effect of independent variables (oil amount, lecithin amount and glycerol amount) toward response variables (particle size, polydispersity index, zeta potential and osmolality) were studied using central composite design (CCD). RSM analysis showed that the experimental data could be fitted into a second-order polynomial model. Chloramphenicol-loaded nanoemulsion was formulated by using high pressure homogenizer. The optimized chloramphenicol-loaded nanoemulsion response values for particle size, PDI, zeta potential and osmolality were 95.33nm, 0.238, -36.91mV, and 200mOsm/kg, respectively. The actual values of the formulated nanoemulsion were in good agreement with the predicted values obtained from RSM. The results showed that the optimized compositions have the potential to be used as a parenteral emulsion to cross blood-brain barrier (BBB) for meningitis treatment.