In vitro and in vivo ocular safety and eye surface permanence determination by direct and Magnetic Resonance Imaging of ion-sensitive hydrogels based on gellan gum and kappa-carrageenan

Gellan gum, kappa-carrageenan and alginates are natural polysaccharides able to interact with different cations that can be used to elaborate ion-activated in situ gelling systems for different uses. The interaction between fluid solutions of these polysaccharides and cations presents into the tear made these biopolymers very interesting to elaborate ophthalmic drug delivery systems. The main purpose of this study is to evaluate the ability of mixtures of these polymers to obtain ion-activated ophthalmic in situ gelling systems with optimal properties for ocular use. To achieve this purpose different proportion of the biopolymers were analyzed using a mixture experimental design evaluating their transparency, mechanical properties and bioadhesion in the absence and presence of simulated tear fluid. Tear induces a rapid sol-to-gel phase transition in the mixtures forming a consistent hydrogel. The solution composed by 80% of gellan gum and 20% kappa-carrageenan showed the best mechanical and mucoadhesive properties. This mixture was evaluated for rheological behavior, microstructure, cytotoxicity, acute corneal irritancy, ex-vivo and in vivo ocular toxicity and in vivo corneal contact time using Magnetic Resonance Images (MRI) techniques. Result indicates that the system is safe at ophthalmic level and produces an extensive ocular permanence higher than 6 h.     

Bioadhesive vaginal drug delivery of nystatin using a derivatized polymer: Development and characterization

Increasing incidence of resistance to azole antifungals has highlighted the importance of the use of alternative therapeutic agents such as nystatin for the treatment of vulvovaginal candidiasis. The aim of the present study was to develop and characterize locally acting, film formulation for the treatment of candidiasis using a derivatized natural polymer. Derivatization of natural polymer was carried out in order to introduce anionic character to an otherwise neutral polymer, so as to enhance its interaction with vaginal mucous membrane along with inheriting the biocompatibility and nonirritant characteristics of its parent polymer. A carboxymethyl derivative of fenugreek gum (CMFG) was prepared, and characterized by DSC, FTIR and X-ray diffraction studies. The derivatized gum was found to possess bioadhesive and film forming properties. A 3² factorial design was employed to formulate vaginal films and a response surface methodological approach was used to study the effect of formulation variables on film properties. Films containing 5% w/v polymer and 2% v/v glycerol exhibited optimum properties in vitro. The optimized drug loaded formulation was able to release 100% drug over a period of 5 h and followed Korsmeyer–Peppas kinetics. It was found to be non-irritant and nontoxic to vaginal mucosa and showed appropriate antifungal properties in vivo.     

桃胶改良前后的溶胀性能分析

目的:阐明溶剂、盐浓度、温度及p H对桃胶改良前后溶胀性能的影响,为阐明其缓释性能提供实验依据。方法:采用称重法测定原桃胶和改良桃胶辅料溶胀前后的干重、湿重,计算平衡溶胀率。结果:在不同溶剂中,改良桃胶的平衡溶胀率普遍明显高于原桃胶;桃胶改良前后的平衡溶胀率为二甲基亚砜水无水乙醇;在不同盐浓度中,桃胶改良前后的平衡溶胀率基本相同,均不受盐浓度影响,但显著小于水;在不同温度中,温度越高,桃胶改良前后的溶胀性能均越大,且改良桃胶更优;在不同p H溶液中,原桃胶易受酸碱度影响,而改良桃胶的平衡溶胀率不受其影响,且表现出更佳的溶胀性能。结论:改良桃胶的溶胀性能显著优于原桃胶;桃胶改良前后的溶胀性能受溶剂、温度的影响显著,而对盐浓度和p H(原桃胶易受影响)则不敏感。     

Engineering of polymer–surfactant nanoparticles of doxycycline hydrochloride for ocular drug delivery

Abstract

Context: Physiologic barriers of the eye, short precorneal drug residence time and poor corneal penetration are the few reasons for reduced ocular bioavailability.

Objective: This study was aimed to develop novel polymer–surfactant nanoparticles of hydrophilic drug doxycycline hydrochloride (DXY) to improve precorneal residence time and drug penetration.

Materials and methods: Nanoparticles were formulated using emulsion cross-linking method and the formulation was optimized using factorial design. The prepared formulation was characterized for particle size, ζ potential, encapsulation efficiency, in vitro drug release and ex vivo drug diffusion studies. The antibacterial activity studies were also carried out against Escherichia coli and Staphylococcus aureus using the cup-plate method. In vivo eye irritation study was carried out by a modified Draize test in rabbits.

Results and discussion: The particle size was found to be in the range of 331–850?nm. About 45–80% of the drug was found to be encapsulated in the nanoparticles. In vitro release demonstrated sustained release profile. Lower flux values in case of nanoparticles as compared to DXY pure drug solution in ex vivo diffusion studies confirmed the sustained release. The nanoparticles were found to be significantly effective (p?<?0.001) than DXY aqueous solution due to sustained release of doxycycline from nanoparticles in both the E. coli and S. aureus strains. The formulation was found to be stable over entire stability period.

Conclusion: The developed formulation is safe and suitable for sustained ocular drug delivery.     

植物胶软胶囊新囊材的研究进展

以植物胶替代明胶作为囊壳制备而成的软胶囊称之为植物胶软胶囊。随着明胶软胶囊的深入应用,其缺点越发突出,因而寻找软胶囊新囊材成为植物胶软胶囊市场发展的必然需求。目前植物胶软胶囊囊材的研究取得了一定的进展,已有多个专利申请成功,但鲜有成熟的产品上市。通过查阅近些年有关植物胶软胶囊的文献报道,本文对研究较为成熟的卡拉胶、淀粉、甘露聚糖胶、黄原胶和海藻酸钠5种植物胶软胶囊囊材进行了分类综述,阐述其凝胶机制及优缺点等。利用各种植物胶的优良性能进行复配,以弥补其单独使用时的缺陷,从而扩大植物胶的使用范围并提高其使用性能。对植物胶软胶囊的应用前景进行讨论与展望,提出其进一步研究方向,为新型植物胶软胶囊的开发应用提供思路与参考。     

Diabetic control is improved by guar gum and wheat bran supplementation

Twenty-eight insulin-dependent diabetics were treated with different dietary regimes for three periods of three months. Initially they used a white flour bread (run-in period), then their daily bread ration was enriched with guar gum (mean dose: 29 g), and then with wheat bran (mean dose: 33 g) in a randomized crossover pattern. Fasting and postprandial blood glucose levels were measured on filter paper spots collected once weekly at home, and other biochemical values were measured monthly. No improvement in diabetic control was seen during the run-in period. Mean postprandial blood glucose decreased from 12.0 +/- 3.8 mmol/l (mean +/- SD) in the run-in period to 9.7 +/- 2.8 mmol/l (p less than 0.01) in the guar period and to 9.7 +/- mmol/l (p less than 0.01) in the bran period. HbA1 decreased from 10.5 +/- 2.1% in the run-in period to 9.7 +/- 1.6% (less than 0.05) at the end of the guar period and 9.9 +/- 1.2% (not significant) at the end of the bran period. Only modest changes were seen in serum-lipids--total cholesterol decreased significantly in the guar period, but not in the bran period. In this study both guar gum and wheat bran were well tolerated and produced a substantial decrease in postprandial blood glucose.     

The use of chewing gum for postoperative ileus prevention in patients undergoing radical cystectomy

Does the postoperative use of chewing gum in patients undergoing radical cystectomy (RC) facilitate intestinal motility recovery, reduce intestinal recanalization times and decrease length of stay? Postoperative ileus is a temporary impairment of intestinal motility and a frequent complication after RC. It is characterized by abdominal distention and absence of bowel functions, with symptoms including nausea, vomiting, pain and cramps. This results in an increase in length of stay, patient discomfort and costs. Different studies investigated the efficacy of chewing gum use, as a form of simulated feeding, in accelerating the resolution of ileus after several abdominal surgical procedures. Considering the lack of specific studies, some other conducted in similar abdominal procedures were included in this literature review. Despite the diversity of type of surgery, all considered studies show for patients who received chewing gum, a significant reduction in the time of first flatus and faeces, a reduction in the time of first bowel movements; not all included studies instead have found a significant decreasing in morbidity and length of stay. The chewing gum use seems to be a simple and inexpensive way to enhance recovery of bowel function, although it is probably still a little known procedure. It is possible recommending the administration of chewing gum in patients after cystectomy, monitoring the effectiveness, upon the recognition of possible conditions that might contraindicate its use.     

Task-induced activation and hemispheric dominance in cerebral circulation during gum chewing

In elderly persons, it is thought that maintenance of masticatory function may have a beneficial effect on maintenance of cerebral function. However, few studies on cerebral circulation during mastication exist. This study aimed to verify a possible increase in cerebral circulation and the presence of cerebral hemispheric dominance during gum chewing. Twelve healthy, young right-handed subjects with normal dentition were enrolled. Bilateral middle cerebral arterial blood flow velocities (MCAV), heart rate, and arterial carbon dioxide levels were measured during a handgrip exercise and gum chewing. During gum chewing, electromyography of the bilateral masseter muscle was recorded.MCAV and heart rate significantly increased during exercise compared to values at rest.During gum chewing, there were no differences in the rate of increase in MCAV between the working and non-working sides, but during the handgrip exercise, the rate of increase in MCAV was significantly greater for the non-working side than for the working side.During gum chewing,muscle activity on the working side was significantly greater than that on the non-working side. These results suggest that during gum chewing, cerebral circulation increases bilaterally and does not show contralateral dominance, as it does during the handgrip exercise.     

Masticatory Performance and Chewing Cycle Kinematics—Are They Related?

Objective:To compare chewing cycle kinematics of subjects with better and poorer masticatory performance.Materials and Methods:A cross-sectional study compared masticatory performance, based on the breakdown of the artificial test food Cuttersil®, in 30 subjects with Class I occlusion. Individuals with median particle sizes greater and lesser than the median value for the entire sample were categorized as poorer (15) and better (15) performers, respectively. While chewing Cuttersil, three-dimensional jaw movements of subjects were tracked with an optoelectric computer system. Multilevel linear modeling was used to evaluate differences in estimated cycle shape, cycle duration, and maximum excursions, as well as within-subject variation between the two groups.Results:Poorer performers had a significantly longer opening duration (0.274 ± 0.225 sec vs 0.325 ± 0.270 sec) than better performers. Poorer and better performers also showed significant differences in cycle shape, including a less horizontal path of closure and more posterior jaw movement in the poorer performers. In addition, poorer performers exhibited significantly more cycle-to-cycle (within-subject) variability in chewing cycle duration, excursive movements, and lateral velocity than did better performers.Conclusions:Poorer performers lacked consistency in their chewing cycles, and their cycle shape differs from that of better performers.