Antibiotic susceptibility profile of uropathogens isolated from pregnant women in selected hospitals in Ilorin

Background: Urinary tract infection (UTI) is one of the most common infections among pregnant women and if untreated could lead to serious complications.Objective: This work was carried out to determine the prevalence rate of Enterobacteriaceae uropathogens and their antibiotics susceptibility profile among pregnant women attending two ante-natal clinics in Ilorin, Nigeria.Materials and Methods: A total of 111 pregnant women between the ages of 18-50 attending ante-natal clinic at University of Ilorin Teaching Hospital and Civil Service Hospital, Ilorin participated in the study. Mid-stream urine samples were collected and cultured on Cysteine-Lactose-Electrolyte Deficient agar. Presence of significant bacteriuria (> 105 cfu/mL) was determined using the plate count method. Antibiotic susceptibility testing was done using Kirby-Bauer disk diffusion technique.Results: Of the 111 urine samples collected, 27.9% of them were found positive on culture. Among the isolated organisms, Klebsiella oxytoca (25.7%) followed by Klebsiella pneumonia (22.9%), were the most prevalent. Isolated bacteria were resistant to at least one antibiotic with the highest resistance seen with amoxicillin (94.3%), streptomycin (77.1%) and nitrofurantoin (54. 3%). Amoxicillin-clavulanic acid (51.4%), ceftriaxone (51.4%), ceftazidime (34.3%), cotrimoxazole (51.4%), imipenem (2.9%), ciprofloxacin (14.3%) and gentamicin (25.7%) have the lowest rate of bacteria resistance. Of the isolates, 82.9% showed Multi-Antibiotic Resistance Index (MARI) ≥ 0.3.Conclusion: High prevalence of bacteriuria in both symptomatic and asymptomatic pregnant women was observed in the study areas. The alarming rate of multi-antibiotic resistance strain is therefore an indicator of a serious clinical problem in the community.Keywords: Bacteriuria, pregnancy, urine culture, antibiotic susceptibilit

Polymer-drug nanoconjugate – an innovative nanomedicine: challenges and recent advancements in rational formulation design for effective delivery of poorly soluble drugs.

The published manuscript is available at EurekaSelect via - See more at: http://dx.doi.org/10.2174/2211738504666160213001714Abstract Background: Over the last four decades, the use of water soluble polymers in rational formulation design has rapidly evolved into valuable drug delivery strategies to enhance the safety and therapeutic effectiveness of poorly soluble drugs, particularly anticancer drugs. Novel advances in polymer chemistry have provided new generations of well defined polymeric architectures for specific applications in polymer-drug conjugate design. However, total control of crucial parameters such as particle size, molecular weight distribution, polydispersity, localization of charges, hydrophilic-lipophilic balance and non site-specific coupling reactions during conjugation has been a serious challenge. Objective: This review briefly describes the current advances in polymer-drug nanoconjugate design and various challenges hindering their transformation into clinically useful medicines. Method: Existing literature was reviewed. Results: This review provides insights into the significant impact of covalent and non-covalent interactions between drug and polymer on drug loading [or conjugation] efficiency, conjugate stability, mechanism of drug release from the conjugate and biopharmaceutical properties of poorly soluble drugs. The utility values and application of Quality by Design principles in rational design, optimization and control of the Critical Quality Attributes [CQA] and Critical Process Parameters [CPP] that underpin the safety, quality and efficacy of the nanoconjugates are also presented. Conclusion: It was apparent that better understanding of the physicochemical properties of the nanoconjugates as well as the drug-polymer interaction during conjugation process is essential to be able to control the biodistribution, pharmacokinetics, therapeutic activity and toxicity of the nanoconjugates which will in turn enhance the prospect of successful transformation of these promising nanoconjugates into clinically useful nanomedicines

Controlled Electrostatic Self-Assembly of Ibuprofen-Cationic Dextran Nanoconjugates Prepared by low Energy Green Process – a Novel Delivery Tool for Poorly Soluble Drugs

Purpose: The direct effect of electrostatic interaction between ibuprofen and cationic dextran on the system-specific physicochemical parameters and intrinsic dissolution characteristics of ibuprofen was evaluated in order to develop drug-polymer nanoconjugate as a delivery strategy for poorly soluble drugs. Methods: Amorphous ibuprofen-DEAE dextran (Ddex) nanoconjugate was prepared using a low energy, controlled amphiphile-polyelectrolyte electrostatic self-assembly technique optimized by ibuprofen critical solubility and Ddex charge screening. Physicochemical characteristics of the nanoconjugates were evaluated using FTIR,DSC,TGA,NMR and SEM relative to pure ibuprofen. The in vitro release profiles and mechanism of ibuprofen release were determined using mathematical models including zero and first order kinetics; Higuchi; Hixson-Crowell and Korsmeyer-Peppas. Results: Electrostatic interaction between ibuprofen and Ddex was confirmed with FT-IR,1HNMR and 13CNMR spectroscopy. The broad and diffused DSC peaks of the nanoconjugate as well as the disappearance of ibuprofen melting peak provided evidence for their highly amorphous state. Low concentrations of Ddex up to1.0×10−6 g/dm3 enhanced dissolution of ibuprofen to a maximum of 81.32% beyond which retardation occurred steadily. Multiple release mechanisms including diffusion; discrete drug dissolution; anomalous transport and super case II transport were noted. Conclusion: Controlled assembly of ibuprofen and Ddex produced a novel formulation with potential extended drug release dictated by Ddex concentration

Formulation studies on ibuprofen sodium–cationic dextran conjugate: effect on tableting and dissolution characteristics of ibuprofen

The effect of electrostatic interaction between ibuprofen sodium (IbS) and cationic diethylaminoethyl dextran (Ddex), on the tableting properties and ibuprofen release from the conjugate tablet was investigated. Ibuprofen exhibits poor flow, compaction (tableting) and dissolution behavior due to its hydrophobic structure, high cohesive, adhesive and viscoelastic properties therefore it was granulated with cationic Ddex to improve its compression and dissolution characteristics. Electrostatic interaction and hydrogen bonding between IbS and Ddex was confirmed with FT-IR and DSC results showed a stepwise endothermic solid–solid structural transformation from racemic to anhydrous forms between 120 and 175 °C which melted into liquid form at 208.15 °C. The broad and diffused DSC peaks of the conjugate granules as well as the disappearance of ibuprofen melting peak provided evidence for their highly amorphous state. It was evident that Ddex improved the flowability and densification of the granules and increased the mechanical and tensile strengths of the resulting tablets as the tensile strength increased from 0.67 ± 0.0172 to 1.90 ± 0.0038 MPa with increasing Ddex concentration. Both tapping and compression processes showed that the most prominent mechanism of densification were particle slippage, rearrangement and plastic deformation while fragmentation was minimized. Ddex retarded the extent of dissolution in general, indicating potentials for controlled release formulations. Multiple release mechanisms including diffusion; anomalous transport and super case II transport were noted. It was concluded that interaction between ibuprofen sodium and Ddex produced a novel formulation with improved flowability, tableting and dissolution characteristics with potential controlled drug release characteristics dictated by Ddex concentration

Thermodynamic Changes Induced by Intermolecular Interaction Between Ibuprofen and Chitosan: Effect on Crystal Habit, Solubility and In Vitro Release Kinetics of Ibuprofen

Purpose: The direct impact of intermolecular attraction between ibuprofen and chitosan on crystal behaviour, saturated solubility and dissolution efficiency of ibuprofen was investigated in order to expand the drug delivery strategy for ibuprofen. Methods: Amorphous nanoparticle complex (nanoplex) was prepared by controlled drug-polymer nanoassembly. Intermolecular attraction was confirmed with surface tension, conductivity measurements and FTIR spectroscopy. The nanoplex was characterized using DSC, TGA and SEM. The in vitro release kinetics and mechanism of drug release were evaluated using mathematical models. Results: The cmc of ibuprofen decreased significantly in the nanoplex (1.85 mM) compared with pure ibuprofen (177.62 mM) suggesting a remarkable affinity between the chitosan and ibuprofen. The disappearance of ibuprofen melting peak in the nanoplex and the broadened DSC endothermic peaks of the nanoplex indicate formation of eutectic amorphous product which corresponded to higher saturated solubility and dissolution velocity. Ibuprofen (aspect ratio 5.16±1.15) was converted into spherical nanoparticle complex with particle size of 14.96±1.162–143.17±17.5247 nm (36–345 folds reduction)dictated by chitosan concentration. Pure ibuprofen exhibited burst release while the nanoplexes showed both fast and extended release profiles. DE increased to a maximum(81.76± 2.1031%) with chitosan concentrations at 3.28×10–3 g/dm3, beyond which retardation occurred steadily. Major mechanism of drug release from the nanoplex was by diffusion however anomalous transport and super case II transport did occur. Conclusion: Ibuprofen-chitosan nanoplex exhibited combined fast and extended release profile dictated by chitosan concentration.This study demonstrated the potential application of drug-polymer nanoconjugate design in multifunctional regulated drug delivery

Development of aqueous ternary nanomatrix films: a novel ‘green’ strategy for the delivery of poorly soluble drugs

Aqueous polymeric films have potentially great values in drug development, particularly in controlled drug release and taste masking strategies. However the progressive polymer-particle coalescence that occurs randomly during film formation, curing and storage may render the film less permeable leading to erratic and unpredictable drug release profile. The focus of this study was to investigate the impacts of the in situ formation of polymer-drug nanoconjugate, at the interfacial nano-domains of two oppositely charged polymers, on the mechanism of film formation and to prepare aqueous ternary polymer-drug-polymer nanomatrix films as a novel green strategy for the delivery of ibuprofen, a model poorly soluble drug. Composite and Layer-by-Layer films were prepared by aqueous casting technique using the concept of combined polymer-drug self-assembly and polyelectrolyte complexation. The plain and drug-loaded nanomatrix films were characterized using SEM, AFM, FTIR, DSC and TGA. Ibuprofen formed spherical core-shell microstructures (4.55 - 9.73 μm) in gellan film. However in the presence of cationic dextran (Ddex), nanoconjugates (61.49±5.97 - 447.52±37.51 nm) were formed within the core of the film matrix. The composite films exhibited reduced tensile strength and lower elastic modulus with optimal conjugation efficiency of 98.14±1.19%, which correlates with higher dissolution efficiency (99.76%) compared to 47.37% in layer-by-layer (LbL) films, dictated by Ddex concentration. Generally, the mechanism of drug release was by Fickian diffusion, however anomalous transport or polymer relaxation was also observed at higher concentration of Ddex. This study demonstrated the potential application of aqueous drug-loaded nanomatrix films as controlled drug delivery strategy for ibuprofen, a model poorly soluble drug

Ex vivo skin permeation and retention studies on chitosan–ibuprofen–gellan ternary nanogel prepared by in situ ionic gelation technique—a tool for controlled transdermal delivery of ibuprofen

The chemical potentials of drug–polymer electrostatic interaction have been utilized to develop a novel ternary chitosan–ibuprofen–gellan nanogel as controlled transdermal delivery tool for ibuprofen. The ternary nanogels were prepared by a combination of electrostatic nanoassembly and ionic gelation techniques. The electrostatic and hydrophobic interactions as well as hydrogen bonding between ibuprofen and chitosan were confirmed with FTIR, while DSC, TGA and SEM confirmed the physical state, thermal and morphological characteristics, respectively. The ex vivo delivery of ibuprofen onto and across the skin was evaluated based on system specific drug release parameters such as steady state permeation rate, permeability coefficient, permeability enhancement ratio, skin/gel partition coefficient, diffusion coefficient, lag time and release rate constant and mechanisms of release were determined using mathematical models. Interaction between ibuprofen and chitosan produced new spherical eutectic nanoconjugates with remarkable decrease in particle size of ibuprofen from 4580 (length-to-breadth aspect ratio) to a minimum of 14.15 nm (324-times), and thermally stable amorphous characteristics. The nanogels exhibited significant elastic and pseudoplastic characteristics dictated by the concentration of chitosan with maximum swelling capacity of 775% w/w at 6.55 mM chitosan compared with 281.16 and 506.50% for plain gellan and control ibuprofen hydrogel, respectively. Chitosan enhanced the skin penetration, permeability and the rate of transdermal release of ibuprofen by a factor of 4, dictated by the extent of ibuprofen–chitosan ionic interaction and its concentration. The major mechanism of ibuprofen release through the pig skin was drug diffusion however drug partition and matrix erosion also occurred. It was evident that ternary nanogels are novel formulations with potential application in controlled transdermal delivery of ibuprofen

Quantification of in situ granulation-induced changes in pre-compression, solubility, dose distribution and intrinsic in vitro release characteristics of ibuprofen–cationic dextran conjugate crystanules

The direct effect of intermolecular association between ibuprofen and diethylaminoethyl dextran (Ddex) and the novel ‘melt-in situ granulation–crystallization’ technique on the solubility, dose distribution, in vitro dissolution kinetics and pre-compression characteristics of the ibuprofen–Ddex conjugate crystanules have been investigated using various mathematical equations and statistical moments. The research intention was to elucidate the mechanisms of ibuprofen solubilization, densification and release from the conjugate crystanules as well as its dose distribution in order to provide fundamental knowledge on important physicochemical, thermodynamic and system-specific parameters which are key indices for the optimization of drug–polymer conjugate design for the delivery of poorly soluble drugs. The process of melt-in situ-granulation–crystallization reduced the solubility slightly compared with pure ibuprofen, however, the ibuprofen–Ddex conjugate crystanules exhibited increased ibuprofen solubility to a maximum of 2.47 Â 10 À1 mM (at 1.25 Â 10 À4 mM Ddex) and 8.72 Â 10 À1 mM (at 6.25 Â 10 À4 mM Ddex) at 25 and 37 C, respectively. Beyond these concentrations of Ddex ibuprofen solubility decreased steadily due to stronger bond strength of the conjugate crystanules. The enthalpy– entropy compensation plot suggests a dominant entropy-driven mechanism of solubilization. In the same vein, the addition of Ddex increased the rate and extent of in vitro ibuprofen release from the conjugate crystanule to 100% within 168 h at Ddex concentration of 1.56 Â 10 À4 mM, followed by a decrease with Ddex concentration. The conjugate crystanules exhibited controlled and extended- complete release profile which appeared to be dictated by the concentration of the Ddex and its strong affinity for ibuprofen. A comparison of the real experimental with the predicted data using artificial neural network shows excellent correlation between solubility and dissolution profiles (average error = 0.2348%). Heckel, Kawakita, Cooper–Eaton and Kuno equations were employed to determine the mechanism of densification during tapping process. Ddex in the crystanules consistently improved particle rearrangement in the order of 2.5–7 folds compared with pure ibuprofen and stabilized ibuprofen against fragmentation during tapping process. Primary and secondary particle rearrangements were the prominent mechanisms of densification while deformation and fragmentation did not occur. Lower concentrations of Ddex below its critical granular concentration (<6.25 Â 10 À4 mM) hindered plastic deformation and fragmentation, however, the summation of primary and secondary rearrangement parameters was greater than unity suggesting that the overall rearrangement of the conjugate crystanules cannot be explained exclusively by these two steps. This study has demonstrated the formulation of a novel ibuprofen–polymer conjugate which exhibited improved dose distribution and pre-compression characteristics as well as controlled and extended-complete release profiles – a potential drug delivery strategy for poorly soluble drugs

Induction of Genotoxicity by Concurrent Exposure to Titanium Dioxide and Zinc Oxide Nanoparticles in Mice

The recent surge in the application of nanotechnology and the specific attractive properties of nanomaterials have led to widespread applications of nanoparticles particularly in life sciences, pharmaceutical, cosmetics and textile industries. This widespread use has also led to worldwide distribution of nanoparticles and consequent increased likelihood of human exposure thereby raising concerns about their safety. Due to the rapid increase in their applications and their exponential industrial production, workers are constantly exposed to these nanoparticles in their workplace. Some previous studies have reported that nanoparticles may generate potential harm to the environment and are both genotoxic and cytotoxic to humans. Other studies argue that they are not. This study therefore aims to assess the genotoxic and cytotoxic potential of a concurrent exposure to nanoparticles using titanium dioxide nanoparticles (TiO2.NPs) and zinc oxide nanoparticles (ZnO.NPs) in mice. Four groups 2 of mice made up of five animals each were exposed to four different concentrations (25 mg/kg body weight (bw); 50 mg/kg bw, 75 mg/kg bw and 100 mg/kg bw) of the nanoparticles. Each concentration comprised 50% titanium oxide nanoparticles and 50% zinc oxide nanoparticles given separately by oral gavaging for five consecutive days while the control group was treated with distilled water. Bone marrow was harvested for micronucleus assay and the incidence of micronuclei in polychromatic erythrocytes was scored per 1,000 cells. The results showed a concentration dependent increase in the frequency of micronuclei occurrence which was statistically significant at the concentration of 100 mg/kg bw (P &lt; 0.05). Also the ratio of polychromatic erythrocytes to normochromatic erythrocytes was statistically significant at this concentration. This result shows that concurrent exposure to titanium oxide nanoparticles and zinc oxide nanoparticles induces both genotoxicity and cytotoxicity in mice.Keywords: Nanoparticles, Titanium oxide, Zinc oxide, genotoxicity, micronucleus, erythrocyte