Bogdan Tamba

Comparison of the pain experienced by infertile women undergoing hysterosalpingo contrast sonography or radiographic hysterosalpingography

To evaluate the pain and cause of pain experienced by women undergoing hysterosalpingography (HSG) and contrast hysterosalpingo sonography (HyCoSy) with air in a saline solution for the assessment of uterine and tubal patency.

In vitro and in vivo behavior of ketoprofen intercalated into layered double hydroxides.

Ketoprofen (Ket) was intercalated into layered double hydroxides (ZnAlLDH and MgAlLDH) using the ionic exchange method. The drug intercalation was confirmed by X-ray diffraction (XRD) and FTIR spectroscopy. Ket release from the inorganic matrix was studied at pH 7.4 in continuous regime with a flow rate of 0.5 and respectively 1.0xa0ml/min. The kinetical data were interpreted using the Ritger and Peppas model. The data prove that the release kinetics and mechanism depend on the eluent flow rate. Quantification of gastric tolerance shows that the ulcerogenic effect of the intercalated drug is lower than the one of the raw Ket. The antinociceptive effect of both formulations was studied by the hot-plate method performed on mice. The MgAlLDH_Ket formulation shows a tendency towards a stronger antinociceptive effect than its ZnAlLDH_Ket counterpart during the 210xa0min recorded period.

Silica nanoparticles: preparation, characterization and in vitro/in vivo biodistribution studies.

BACKGROUNDnThe current progress in pharmaceutical nanotechnology field has been exploited in the design of functionalized radiolabelled nanoparticles that are able to deliver radionuclides in a selective manner to improve the outcome of diagnosis and treatment. Silica nanoparticles (SNPs) have been widely developed for biomedical applications due to their high versatility, excellent functional properties and low cost production, with the possibility to control different topological parameters relevant for multidisciplinary applications.nnnPURPOSEnThe aim of the present study was to characterize and evaluate both in vitro, by microscopy techniques, and in vivo, by scintigraphic imaging, the biodistribution of silica nanostructures derivatives (Cy5.5 conjugated SNPs and (99m)Tc radiolabelled SNPs) to be applied as radiotracers in biomedicine.nnnMETHODSnSNPs were synthesized by hydrolysis and condensation of silicon alkoxides, followed by surface functionalization with amino groups available for fluorescent dye and radiolabelling possibility.nnnRESULTSnOur data showed the particles size distribution (200-350 nm), the surface charge (negative for bare and fluorescent SNPs and positive for amino SNPs), polydispersity index (broad distribution), the qualitative composition and the toxicity assessments (safe material) that made the obtained SNPs candidates for in vitro/in vivo studies. A high uptake of fluorescent SNPs in all the investigated organs was evidenced by confocal microscopy. The (99m)Tc radiolabelled SNPs biodistribution was quantified in the range of 12-100% counts/g organ using the scintigraphic images.nnnCONCLUSIONSnThe obtained results reveal improved properties, namely, reduced toxicity with a low level of side effects, an improved biodistribution, high labelling efficiency and stability of the radiolabelled SNPs with potential to be applied in biomedical science, particularly in nuclear medicine as a radiotracer.

Formulation and evaluation of cefuroxim loaded submicron particles for ophthalmic delivery.

Chitosan gelatin particles could be the ideal candidate for intraocular drug delivery due to their desirable properties. Double crosslinking in double emulsion has been used as an original and reliable method for particles preparation and their morphology has been optimized considering the main synthesis parameters such as polymers ratio, crosslinker amount, stirring speed, tensioactive amount and ionic crosslinking time, respectively. The particles have been analyzed for their physical-chemical properties (swelling degree, drug loading and release capacity, surface characteristics, etc.), the enzymatic degradation properties along with in vivo ocular investigations (ocular biodistribution, in vivo drug release). In the present study cefuroxim was used as a model drug, which is generally used in the prophylaxis of postoperative endophthalmitis following cataract surgery after intraocular administration. The present study proved that the dimensions and the physical-chemical properties of the particles can be modulated (by varying the preparation parameters) to facilitate the administration, the biodistribution and the drug release in the specific segment of the eye. This experimental study demonstrated also the ability of fluorescent nanoparticles to penetrate ocular tissues close to the administration site (intravitreal injection) and especially their tendency to migrate deep in the retina at time intervals of 72 h.

Levonorgestrel releasing-intrauterine system for the treatment of menorrhagia and/or frequent irregular uterine bleeding associated with uterine leiomyoma

ABSTRACT Objective To evaluate the effectiveness of the levonorgestrel releasing-intrauterine system (LNG-IUS) in the treatment of menorrhagia and/or frequent irregular uterine bleeding in women with uterine myomas. Study design Prospective study whereby 102 women with intramural myomas (in a few cases associated with submucous or subserous myomas), suffering from menorrhagia and/or frequent irregular uterine bleeding, were evaluated by means of the Pictorial Blood Assessment Chart (PBAC; Higham score) and ultrasound, three, six and 12 months after insertion of a LNG-IUS. Results The PBAC score dropped (from a mean value of 231.7 to 17.6 at 12 months). The duration of menstrual bleeding diminished significantly (p < 0.001). Uterine volume decreased from a mean of 145 cm³ to 129 cm³ at 12 months (p = 0.01). Changes in the volume of the myomas were not statistically significant (p = 0.23). Satisfaction rate was good in 91 cases (89%), fair in four cases (4%), and poor in seven cases (7%). During the one-year period of follow-up, 11 cases of expulsion or removal of the LNG-IUS were recorded. Conclusion The LNG-IUS is effective in controlling heavy menorrhagia and/or frequent irregular uterine bleeding related to the presence of myomas, but has no significant effect on the size of the tumours.

Flaxseed lignan wound healing formulation: Characterization and in vivo therapeutic evaluation

Flaxseed lignans are a natural source of useful biologically active components that show a diverse spectrum of health-promoting properties. The valuable effects of the phenolic molecules are mainly due to their antioxidant activity by preventing oxidative stress and stimulate collagen synthesis, therefore, providing benefits to the skin. The present work highlights the development of flaxseed extract formulation as novel wound healing agent. The recognition of key structural features within flaxseed extract was crucial for the design and development of the therapeutic cream. Chromatographic analyses were employed for bioactive compounds identification and quantification. Folin-Ciocalteu method determined the total phenolic content and the antioxidant properties were evaluated by DPPH assay. The storage and loss modulus and tan δ were calculated for cream rheological properties evaluation. In vitro diffusion capacity and in vivo wound healing activity of phenolic cream were evaluated on Wistar rats. The collective properties and healing effect of the flaxseed suggested wound healing capacity.

Common trace elements alleviate pain in an experimental mouse model

Trace elements represent a group of essential metals or metaloids necessary for life, present in minute amounts. Analgesic adjuvants can enhance the effect of other pain drugs or be used for pain control themselves. Previous studies on the effects of trace elements on nociception and their potential use as analgesic adjuvants have yielded conflicting results. In this study, we tested the hypothesis that three vital trace elements (Zn2+, Mg2+, Cu2+) have direct antinociceptive effects. Groups of eight Swiss mice were intraperitoneally (i.p) injected with incremental concentrations of Zn2+ sulfate (0.5, 2.0 mg/kg), Zn2+ citrate (0.125, 0.5 mg/kg), Mg2+ chloride (37.5, 75, 150 mg/kg), Cu2+ chloride (0.5, 1.0, 2.0 mg/kg), and Cu2+ sulfate (0.5, 1.0 mg/kg) or saline (control). Evaluations were made by hot plate (HP) and tail flick (TF) tests for central antinociceptive effect, writhing test (WT) for visceral antinociceptive effect, and activity cage (AC) test for spontaneous behavior. Zn2+ induced pain inhibition in HP/TF tests (up to 17%) and WT (up to 25%), with no significant differences among the salts used. Mg2+ salts induced pain inhibition for all performed tests (up to 85% in WT). Cu2+ salts showed antinociceptive effects for HP/TF (up to 28.6%) and WT (57.28%). Only Mg2+ and Cu2+ salts have displayed significant effects in AC (Mg2+ anxiolytic/depressant effect; Cu2+ anxiolytic effect). We interpret these data to mean that all tested trace elements induced antinociceptive effects in central and visceral pain tests. Our data indicate the potential use of these cheap adjuvants in pain therapy.

Carboxymethyl guar gum nanoparticles for drug delivery applications: Preparation and preliminary in-vitro investigations.

Carboxymethyl guar gum (CMGG) synthesized from commercially available polysaccharide was formulated into nanoparticles via ionic gelation using trisodium trimetaphosphate (STMP) as cross-linking agent. Characterisation using a range of analytical techniques (FTIR, NMR, GPC, TGA and DLS) confirmed the CMGG structure and revealed the effect of the CMGG and STMP concentration on the main characteristics of the obtained nanoformulations. The average nanoparticle diameter was found to be around 208 nm, as determined by dynamic light scattering (DLS) and confirmed by scanning electron microscopy (SEM) and nanoparticle tracking analysis (NTA). Experiments using simulated gastric and intestinal fluids evidenced significant pH-dependent drug release behaviour of the nanoformulations loaded with Rhodamine B (RhB) as a model drug (loading capacity in excess of 83%), as monitored by UV-Vis. While dose-dependent cytotoxicity was observed, the nanoformulations appeared completely non-toxic at concentrations below 0.3 mg/mL. Results obtained so far suggest that carboxymethylated guar gum nanoparticles formulated with STMP warrant further investigations as polysaccharide based biocompatible drug nanocarriers.

Enhanced analgesic effects of tramadol and common trace element coadministration in mice

Chronic pain is managed mostly by the daily administration of analgesics. Tramadol is one of the most commonly used drugs, marketed in combination with coanalgesics for enhanced effect. Trace elements are frequent ingredients in dietary supplements and may enhance tramadols analgesic effect either through synergic mechanisms or through analgesic effects of their own. Swiss Weber male mice were divided into nine groups and were treated with a combination of the trace elements Mg, Mn, and Zn in three different doses and a fixed dose of tramadol. Two groups served as positive (tramadol alone) and negative (saline) controls. Nociceptive assessment by tail‐flick (TF) and hot‐plate (HP) tests was performed at baseline and at 15, 30, 45, and 60 min after intraperitoneal administration. Response latencies were recorded and compared with the aid of ANOVA testing. All three trace elements enhanced tramadols analgesic effect, as assessed by TF and HP test latencies. Coadministration of these trace elements led to an increase of approximately 30% in the average pain inhibition compared with the tramadol‐alone group. The most effective doses were 0.6 mg/kg b.w. for Zn, 75 mg/kg b.w. for Mg, and 7.2 mg/kg b.w. for Mn. Associating trace elements such as Zn, Mg, and Mn with the standard administration of tramadol increases the drugs analgesic effect, most likely a consequence of their synergic action. These findings impact current analgesic treatment because the addition of these trace elements may reduce the tramadol dose required to obtain analgesia.

Ibuprofen-loaded chitosan/poly(maleic anhydride-alt-vinyl acetate) submicronic capsules for pain treatment

A new approach to prepare polymeric capsules was developed to obtain an efficient controlled release system for pain treatment. Capsules with a mean diameter between 400 and 1000 nm were prepared using an interfacial condensation method between a natural polymer, chitosan, and a synthetic one, poly(maleic anhydride-alt-vinyl acetate). The influence of different reaction parameters on capsule diameter and properties was investigated. Zeta-potential determinations indicated a good stability of the capsules in aqueous solution containing KCl. Scanning electron microscopy confirmed the submicron dimensions and the spherical shape of the capsules. The thermal properties of the capsules were determined by differential scanning calorimetry and thermogravimetric analysis. In addition, these particles presented a good swelling capacity, which was influenced by the reaction parameters used in this study (molar ratio between the two polymers, the volume ratio between aqueous and organic phase, the amount of surfactant and the reaction time). The ibuprofen loading and release capacity were influenced by the swelling degree. In vivo, the ibuprofen-loaded capsules presented a delayed effect in peripheral pain inhibition and a sustained effect in central pain inhibition.