RATIONAL FOR THE USE OF COCONUT OIL-BASED ANTI-MYCOTIC PESSARIES TO COMBAT RECURRENT VAGINAL INFECTION: IN VITRO/IN VIVO EVALUATION AND PRELIMINARY PROSPECTIVE CLINICAL INVESTIGATION

Objective: Coconut oil (CO) was used in combination with metronidazole in order to prepare vaginal pessaries ameliorating the use, delivery and efficacy of the anti-mycotic treatment. Methods: To prepare the metronidazole–loaded pessaries, different lipids, namely: suppocire NA15 (SNA), suppocire NAIS10 (SIS), suppocire AM (SAM) and ovucire WL 2944 (OWL) were used alone or in combination with coconut oil in a ratio of 1:1. Prepared pessaries were subjected to characterization and evaluation of physical properties, drug release, anti-microbial effect, in vivo studies and histopathological examination. Results: In the case of all the lipids, coconut oil improved the physical properties which can allow better use and performance of the pessaries. Among the prepared pessaries, the OWL/CO-based pessary (P8) showed the highest drug release profile (P<0.05). Characterization was done using X-Ray diffraction. Microbiological study showed the superiority of OWL/CO-based pessaries over OWL-based pessaries at different time intervals. Histopathological studies of the vagina of female Wistar rats showed that in the case of the Candida albicans-infected group treated with the selected pessary, the mucosal and muscular layer returned to its normal structure, in addition to the disappearance of the cauliflower-like projections and the newly formed blood capillaries, seen in the Candida albicans-infected group. The questionnaire done in volunteers suffering from recurrent vaginal infection reported a significant decrease (reaching 93 %) in the severity of the symptoms, after the use of the suggested pessaries (P8) (P<0.05). Also, the suggested product had high patient acceptability. The results reported after the use of P8 were better than those of Amrizole® vaginal suppository. Conclusion: The current study can present a successful, effective and easy to use product with low cost and minimal side effects

Nanolipogel Loaded with Tea Tree Oil for the Management of Burn: GC-MS Analysis, In Vitro and In Vivo Evaluation

The GC-MS analysis of tea tree oil (TTO) revealed 38 volatile components with sesquiterpene hydrocarbons (43.56%) and alcohols (41.03%) as major detected classes. TTO efficacy is masked by its hydrophobicity; nanoencapsulation can address this drawback. The results showed that TTO-loaded solid lipid nanoparticles (SLN1), composed of glyceryl monostearate (2% w/w) and Poloxamer188 (5% w/w), was spherical in shape with a core-shell microstructure. TTO-SLN1 showed a high entrapment efficiency (96.26 ± 2.3%), small particle size (235.0 ± 20.4 nm), low polydispersity index (0.31 ± 0.01), and high negative Zeta potential (−32 mV). Moreover, it exhibited a faster active agent release (almost complete within 4 h) compared to other formulated TTO-SLNs as well as the plain oil. TTO-SLN1 was then incorporated into cellulose nanofibers gel, isolated from sugarcane bagasse, to form the ‘TTO-loaded nanolipogel’ which had a shear-thinning behavior. Second-degree thermal injuries were induced in Wistar rats, then the burned skin areas were treated daily for 7 days with the TTO-loaded nanolipogel compared to the unmedicated nanolipogel, the TTO-loaded conventional gel, and the normal saline (control). The measurement of burn contraction proved that TTO-loaded nanolipogel exhibited a significantly accelerated skin healing, this was confirmed by histopathological examination as well as quantitative assessment of inflammatory infiltrate. This study highlighted the success of the proposed nanotechnology approach in improving the efficacy of TTO used for the repair of skin damage induced by burns

β-Sitosterol Glucoside-Loaded Nanosystem Ameliorates Insulin Resistance and Oxidative Stress in Streptozotocin-Induced Diabetic Rats

β-Sitosterol glucoside (SG), isolated from Senecio petasitis (Family Asteraceae), was loaded in self-nanoemulsifying drug delivery systems (SEDDS) in a trial to enhance its solubility and biological effect. Various co-surfactants were tested to prepare a successful SEDDS. The selected SG-loaded SEDDS had a droplet size of 134 ± 15.2 nm with a homogenous distribution (polydispersity index 0.296 ± 0.02). It also demonstrated a significant augmentation of SG in vitro release by 4-fold compared to the free drug suspension. The in vivo insulin sensitivity and antidiabetic effect of the prepared SG-loaded SEDDS were further assessed in streptozotocin-induced hyperglycemic rats. The hypoglycemic effect of SG-loaded nanosystem was evidenced by decreased serum glucose and insulin by 63.22% and 53.11%, respectively. Homeostasis model assessment-insulin resistance (HOMA-IR) index demonstrated a significant reduction by 5.4-fold in the diabetic group treated by SG-loaded nanosystem and exhibited reduced glucagon level by 40.85%. In addition, treatment with SG-loaded nanosystem significantly decreased serum MDA (malondialdehyde) and increased catalase levels by 38.31% and 64.45%, respectively. Histopathological investigations also supported the protective effect of SG-loaded nanosystem on the pancreas. The promising ability of SG-loaded nanosystem to ameliorate insulin resistance, protect against oxidative stress, and restore pancreatic β-cell secretory function warrants its inclusion in further studies during diabetes progression

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Preparation and in vitro evaluation of rutin nanostructured liquisolid delivery system

Poor aqueous solubility of chemical entities presents a major challenge to modern drug delivery, because of their low bioavailability. Our aim was to prepare and evaluate a suitable solid self-emulsifying drug delivery system (SSEDDS) as a potential carrier for rutin. After screening of various vehicles (surfactants, co-surfactants and oils) and selection of those having the better drug solubilizing power, liquid SEDDS were formulated. Prepared formulations were evaluated for self-emulsifying ability and phase diagrams were constructed to optimize the systems. System (S6), prepared from Triton/Acconon/Labrafac, attained highest drug solubilization capacity, hence, was selected for the preparation of SSEDDS by adsorption on different nano-structured carriers (Neusilin®, Fujicalin® and F-melt®) in different ratios. S6 had a very small particle size of 4.849 ± 0.001 nm and a high percentage transmittance of 99.31 ± 0.16%. SSEDDS showing good flow properties as well as reasonable drug loading capacity were selected for in vitro drug release studies. The SSEDDS (SS4) composed of Neusilin® US2: S6 (1:2) attained the best drug release properties and was subjected to further characterization (SEM, FTIR and XRD). Conclusion: The optimized liquisolid dosage form of rutin provided good flowability as well as fast drug release properties and, therefore, can be suitable for oral delivery system

A Novel Method for Preparing Surface-Modified Fluocinolone Acetonide Loaded PLGA Nanoparticles for Ocular Use: In Vitro and In Vivo Evaluations

Our objective was to prepare nanoparticulate system using a simple yet attractive innovated method as an ophthalmic delivery system for fluocinolone acetonide to improve its ocular bioavailability. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by adopting thin film hydration method using PLGA/poloxamer 407 in weight ratios of 1:5 and 1:10. PLGA was used in 75/25 and 50/50 copolymer molar ratio of DL-lactide/glycolide. Results revealed that using PLGA with lower glycolic acid monomer ratio exhibited high particle size (PS), zeta potential (ZP) and drug encapsulation efficiency (EE) values with slow drug release pattern. Also, doubling the drug concentration during nanoparticles preparation ameliorated its EE to reach almost 100%. Furthermore, studies for separating the un-entrapped drug in nanoparticles using centrifugation method at 20,000 rpm for 30 min showed that the separated clear supernatant contained nanoparticles encapsulating an important drug amount. Therefore, separation of un-entrapped drug was carried out by filtrating the preparation using 20-25 μm pore size filter paper to avoid drug loss. Aiming to increase the PLGA nanoparticles mucoadhesion ability, surface modification of selected formulation was done using different amount of stearylamine and chitosan HCl. Nanoparticles coated with 0.1% w/v chitosan HCl attained most suitable results of PS, ZP and EE values as well as high drug release properties. Transmission electron microphotographs illustrated the deposition of chitosan molecules on the nanoparticles surfaces. Pharmacokinetic studies on Albino rabbit's eyes using HPLC indicated that the prepared novel chitosan-coated PLGA nanoparticles subjected to separation by filtration showed rapid and extended drug delivery to the eye

Development and optimization of self-assembling nanosystem for intra-articular delivery of indomethacin

Osteoarthritis is a propagated debilitating condition affecting patients' quality of life. Intra-articular injection approach was investigated as a localized treatment strategy providing: site-specific delivery, decreased side effects and, increased patient compliance. A 32 full factorial experimental design was employed to prepare the indomethacin-loaded self-assembling nanosystems (SANS). The surfactant (Poloxamer 407/Tetronic 90R4) ratio and the poly(lactic-co-glycolic acid) (PLGA) concentration significantly affected encapsulation efficiency and drug release (p<0.05). The optimized formula was subjected to modification by addition of different proteoglycans, as a compensatory treatment, to improve its pharmacological properties. The modified SANS, containing glucosamine (150 mg), was selected for in-vivo studies as it had a sustained drug release profile and a small particle size (173.90 nm). The effect of the optimized SANS, with or without PLGA, was compared with the modified formula containing glucosamine and, with the drug suspension on the arthritic knee joints of rats. It was found that the formulation containing PLGA and glucosamine showed significantly higher reduction in both, knee diameter and TNF-α levels, compared to other groups. Furthermore, all SANS showed histological improvement in the cellularity of the synovial membranes and joints. Our results indicate that SANS containing PLGA and glucosamine is capable of treating arthritic joints

Nanocellulose: From an agricultural waste to a valuable pharmaceutical ingredient

International audienceCellulose was and still is the most abundant biopolymer generated from all plant fibers including agricultural wastes. Using this waste as a starting material in the production of new products is a field of great interest. The demand for renewable and available resources in combination with advanced technologies is a necessity to develop new generations of advanced nanomaterials. This review aims to present integrated details on the extraction techniques and structure of nanofibrillated cellulose as well as cellulose nanocrystals derived from agricultural wastes besides the different treatment methods used to be suitable for several pharmaceutical applications. Different pharmaceutical applications are described, including controlled, sustained or rapid drug delivery, stabilizing agent, and its use as safe and sustained environment for cell culture allowing its use in tissue engineering field

A trial for the design and optimization of pH-sensitive microparticles for intestinal delivery of cinnarizine

The aim of this study was to formulate a microparticulate delivery system to deliver cinnarizine (CIN) directly to its site of absorption to overcome its low oral bioavailability. Enteric microparticles were prepared by varying ratios of pH-sensitive polymers (Eudragit L100 and Eudragit S100). A full 3(3) factorial experimental design was adopted to evaluate the effect of variables (CIN concentration as well as Eudragit's concentration) on the tested parameters, namely, particle size (p.s.), drug entrapment efficiency (E.E.), and release efficiency (R.E.). Optimization was done using Design Expert® software to maximize E.E. and R.E. and minimize p.s. The optimized formula was characterized using scanning electron microscopy, differential scanning calorimetry, and X-ray diffractometry. In vivo studies conducted on human volunteers using LC-MS analysis revealed improved bioavailability of CIN-loaded enteric microparticles compared to the market product as detected from calculated pharmacokinetic parameters. This study reveals the usefulness of site-specific delivery of CIN