Controlled Insulin Release from Chitosan Microparticles

This study deals with the production of chitosan microparticles containing insulin by interfacial crosslinkage of chitosan solubilized in the aqueous phase of a water/oil dispersion in the presence of ascorbyl palmitate. The use of ascorbyl palmitate as interfacial crosslinker is based on its amphiphilic properties allowing its disposition at the water/oil interface of the preparative dispersion, thus permitting covalent bond formation with the amino groups of chitosan when its oxidation to dehydroascorbyl palmitate takes place during microparticle preparation. This preparation method produced microparticles characterized by high loading levels of insulin, completely releasing the drug in about 80 h at an almost constant release rate as determined by spectrophotometric and spectrofluorimetric methods. In contrast, the replacement of ascorbyl palmitate by dehydroascorbyl palmitate provided microparticles incompletely releasing the incorporated drug and characterized by a non-constant release rate over time due to the higher lipophilicity of dehydroascorbyl palmitate which hinders its disposition at the water/oil interface and thus decreases the crosslinking efficiency and increases the lipophilicity of the microparticle surface. The efficiency of the spectrofluorimetric and spectrophotometric methods used for determination of the stability and release of the insulin from the chitosan microparticles is also discussed.     

Multifunctional Medicated Lyophilised Wafer Dressing for Effective Chronic Wound Healing

Wafers combining weight ratios of Polyox with carrageenan (75/25) or sodium alginate (50/50) containing streptomycin and diclofenac were prepared to improve chronic wound healing. Gels were freeze-dried using a lyophilisation cycle incorporating an annealing step. Wafers were characterised for morphology, mechanical and in vitro functional (swelling, adhesion, drug release in the presence of simulated wound fluid) characteristics. Both blank (BLK) and drug-loaded (DL) wafers were soft, flexible, elegant in appearance and non-brittle in nature. Annealing helped to improve porous nature of wafers but was affected by the addition of drugs. Mechanical characterisation demonstrated that the wafers were strong enough to withstand normal stresses but also flexible to prevent damage to newly formed skin tissue. Differences in swelling, adhesion and drug release characteristics could be attributed to differences in pore size and sodium sulphate formed because of the salt forms of the two drugs. BLK wafers showed relatively higher swelling and adhesion than DL wafers with the latter showing controlled release of streptomycin and diclofenac. The optimised dressing has the potential to reduce bacterial infection and can also help to reduce swelling and pain associated with injury due to the anti-inflammatory action of diclofenac and help to achieve more rapid wound healing. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1720-1733, 2014     

Preparation, Characterization, and Release of Amoxicillin from Electrospun Fibrous Wound Dressing Patches

Purpose

To produce electrospun polymeric fibrous wound dressing patches that can release the antibiotic drug amoxicillin in a controlled manner.

Methods

Poly(D,L-lactide-co-glycolide) acid (PLGA) fibrous dressings with entrapped amoxicillin were produced by electrospinning. The morphology and successful entrapment of amoxicillin in the PLGA fibrous dressings were validated by scanning electron microscopy (SEM) and Fourier Transform Infrared (FTIR) spectroscopy. The rate of drug release from the dressing patches was measured in various media for a period of 21 days using UV spectroscopy.

Results

PLGA fibres entrapping amoxicillin were collected for 300 s and then cut to form square patches with an average weight of 55 mg. Each dressing patch contained ~2 mg of amoxicillin. The mean fibre diameter was 2.2?±?0.4 μm. The drug release from the PLGA dressings was found to be different for each medium during the 21-day release period with the highest and lowest concentration of drug released observed when the dressings were immersed in simulated body fluid (SBF) and phosphate buffered saline (PBS), respectively.

Conclusions

The release profiles obtained in this study and the well-established biocompatibility of PLGA indicate that the fibre-based patches with entrapped amoxicillin fabricated in this work are very well suited for applications in wound healing and infection control.     

美宝创面速愈贴治疗糖尿病足溃疡的临床疗效观察

目的评价美宝创面速愈贴治疗糖尿病足溃疡的有效性。方法共纳入11例患者,随机分为两组,在均继续给予胰岛素和(或)口服降糖药控制血糖及降血脂、血压,同时给予抗血小板,改善微循环,营养神经抗感染等治疗前提下,分别使用美宝创面速愈贴(治疗组,n=6)和常规换药法(对照组,n=5)局部处理糖尿病足溃疡,观察12周。结果治疗组溃疡愈合、显效率明显优于对照组(P<0.05)。结论美宝创面速愈贴用于治疗糖尿病足溃疡有较好疗效。     

吗啡控释片治疗癌性疼痛的疗效和安全性评价

目的：通过Meta分析,评估吗啡控释片直肠给药在癌性疼痛治疗中的临床应用价值。方法：检索中国生物医学文献库（CBMdisc）、中国期刊全文数据库、维普数据库（VIP）等国内数据库已发表的相关文献,收集国内有关吗啡控释片直肠给药治疗癌性疼痛的临床随机、对照试验（randomized controlled trials,RCT）,由2位评价者分别按检索策略收集并纳入标准入选资料,分析指标为疼痛缓解率和不良反应发生率。结果：8个研究共598例患者纳入分析,吗啡控释片直肠给药和口服给药的疼痛缓解率分别是83.69%和87.97%（P=0.09）;在不良反应方面,吗啡控释片直肠给药导致便秘的发生率降低了15%（P〈0.000 1）,消化道反应的发生率降低了21%（P〈0.000 1）,嗜睡头晕的发生率降低了9%（P=0.001）。结论：吗啡控释片直肠给药和口服给药治疗中重度癌性疼痛的效果相近,但直肠给药不良反应的发生率可能较低,临床医生应根据患者个体情况合理选用。     

Controlled Release of Lidocaine from Injectable Gels and Efficacy in Rat Sciatic Nerve Block

Purpose. Methods of delaying the action of local anesthetics are important, since short duration of action limits their use in the treatment of postoperative and chronic pain. The present study evaluated the use of low-viscosity gels in prolonging the release of lidocaine. Methods. Release of lidocaine from 2% lidocaine-HC1 containing methylcellulose (MC), hydroxypropylmethylcellulose (HPMC), sodiumcarboxymethyl cellulose (CMC), and poloxamer 407 (PO) gels was studied in phosphate buffer, pH 7.4, at 37°C. Commercial metylcellulose gel (MC_com) served as control. The in vivo efficacy of the respective gel formulations were evaluated in rats. The gel was injected into the vicinity of the sciatic nerve and nociception and motor function were tested. Results. The cumulative amount of lidocaine released during 8 hr was slowest from the PO gel, followed by the CMC, HPMC and MC gels. The antinociceptive effect was not prevented by the motor block and lasted longest with the PO gel. Good linear and rank order correlation was obtained between in vitro and in vivoresults. The microscopic examination of the tissue samples revealed only mild or no irritation of the skeletal muscle tissue by the PO, HPMC, and CMC gels. Conclusions. Based on these results poloxamer gel proved to be the most promising carrier for lidocaine.     

Sustained Release of Amoxicillin from Chitosan Tablets

Sustained release systems in the forms of chitosan (CTS) tablet and extrude for releasing amoxicillin were studied. The degradation of amoxicillin in pH 1.2 was determined. The effects of particle sizes of chitosan on the dissolution profiles were investigated. The result showed that chitosan with the particle size less than 75 microm yielded the best controlled release pattern and it was comparable to that was obtained from the hydroxypropylmethylcellulose (HPMC) tablets. Moreover, the tablets containing chitosan with particle size less than 75 microm were able to provide a significantly improved sustained release profile of amoxicillin compared to the release profile of a commercial capsule. All release profiles of amoxicillin from the chitosan tablets could be described by first-order kinetics.     

Controlled Release of Ferric-Magnesium Ions From Chitosan/Polyethylene Vinyl Acetate Comatrix for Preventing Pericardial Calcification

Ferric and magnesium ions were embedded in chitosan/polyethylene vinyl acetate comatrix to develop a prolonged release form. The in vitro release profiles of these ions from the comatrix system were monitored in Tris-HCl buffer, pH 7.4, using an ultraviolet (UV) spectrophotometer. The amount of Fe3+ and Mg2+ ions released was initially much higher, followed by a constant slow release profile for a prolonged period. The initial burst release was substantially modified with glutaraldehyde cross-linking of chitosan beads and subsequent styrene butadiene (SBR) coatings on the comatrix. Prostaglandin E was immobilized on this matrix via free1 radical mechanisms, using N plasma to improve their biocompat2 ibility. From scanning electron microscopy studies it appears that the Fe3+/Mg2+ ions diffuse out slowly to the dissolution medium through the micropores of the comatrix. The released Fe3+/Mg2+ ions from the comatrix system had substantially inhibited the pericardial tissue associated calcification, in an in vitro model system. The result proposes the possibility of delivering drug combinations having synergestic effects for therapeutic applications.     

Wound Healing Potential of Formulated Extract from Hibiscus Sabdariffa Calyx

Wound healing agents support the natural healing process, reduce trauma and likelihood of secondary infections and hasten wound closure. The wound healing activities of water in oil cream of the methanol extract of Hibiscus sabdariffa L. (Malvaceae) was evaluated in rats with superficial skin excision wounds. Antibacterial activities against Pseudomonas aeroginosa, Staphylococcus aureus and Echerichia coli were determined. The total flavonoid content, antioxidant properties and thin layer chromatographic fingerprints of the extract were also evaluated. The extract demonstrated antioxidant properties with a total flavonoid content of 12.30±0.09 mg/g. Six reproducible spots were obtained using methanol:water (95:5) as the mobile phase. The extract showed no antimicrobial activity on the selected microorganisms, which are known to infect and retard wound healing. Creams containing H. sabdariffa extract showed significant (P<0.05) and concentration dependent wound healing activities. There was also evidence of synergism with creams containing a combination of gentamicin and H. sabdariffa extract. This study, thus, provides evidence of the wound healing potentials of the formulated extract of the calyces of H. sabdariffa and synergism when co-formulated with gentamicin.     

Controlled Release of Ferric-Magnesium Ions From Chitosan/Polyethylene Vinyl Acetate Comatrix for Preventing Pericardial Calcification

Ferric and magnesium ions were embedded in chitosan/polyethylene vinyl acetate comatrix to develop a prolonged release form. The in vitro release profiles of these ions from the comatrix system were monitored in Tris-HCl buffer, pH 7.4, using an ultraviolet (UV) spectrophotometer. The amount of Fe3+ and Mg2+ ions released was initially much higher, followed by a constant slow release profile for a prolonged period. The initial burst release was substantially modified with glutaraldehyde cross-linking of chitosan beads and subsequent styrene butadiene (SBR) coatings on the comatrix. Prostaglandin E was immobilized on this matrix via free1 radical mechanisms, using N plasma to improve their biocompat2 ibility. From scanning electron microscopy studies it appears that the Fe3+/Mg2+ ions diffuse out slowly to the dissolution medium through the micropores of the comatrix. The released Fe3+/Mg2+ ions from the comatrix system had substantially inhibited the pericardial tissue associated calcification, in an in vitro model system. The result proposes the possibility of delivering drug combinations having synergestic effects for therapeutic applications.     

复方苦参注射液联合盐酸羟考酮控释片治疗癌性疼痛的临床观察

目的:观察复方苦参注射液配合盐酸羟考酮控释片治疗癌性疼痛的临床疗效,尤其是对湿浊内阻及气血亏虚型癌性疼痛患者镇痛的临床疗效。方法:300例癌性疼痛患者按入院顺序随机分为对照组(盐酸羟考酮控释片)、治疗组(盐酸羟考酮控释片+复方苦参注射液),根据治疗组患者症状及舌苔脉象情况,再次分为湿浊内阻组及气血亏虚组。治疗前后根据WHO疼痛程度分级(VRS)标准进行疼痛评价,比较治疗后各组间疼痛缓解率的差别。结果:治疗组镇痛显效率为83.33%,对照组镇痛显效率为74.67%,治疗组镇痛显效率明显高于对照组,差异具有统计学意义(P<0.05)。显效率方面,治疗组高于对照组,差异具有统计学意义(P<0.05);而治疗组中,湿浊内阻组的显效率为88.0%;气血亏虚组显效率为78.67%。结论:复方苦参注射液联合盐酸羟考酮控释片对癌性疼痛具有很好的疗效,尤其对湿浊内阻型癌性疼痛的疗效更佳。     

表皮生长因子对兔眼角膜修复作用的量效关系研究

用角膜表皮刮磨方法人工造成兔眼角膜创伤直径为10mm的圆形创面，分析小鼠表皮生长因子（EGF）对其修复的剂量关系。5个浓度EGF（100、50、20、10和0．5μm／ml）治疗的试验组痊愈时间均比对照组提前，有非常显著的差异（P＜0.01），但在这5个浓度组之间，痊愈时间无显著性差异。结果表明，小鼠EGF对兔眼角膜损伤有促修复作用，实验所用的5个浓度与修复作用无剂量依赖关系。     

Wound Healing Properties of Triterpenes from Buddleia scordioides in Diabetic Rats

Abstract

The pentacyclic triterpenes 3-O-α-l-rhamnopyranosyl-(1 → 4)-β -d-glucopyranosyl-(1 → 3)-[β -d-glucopyranosyl-(1 → 2)]-β -d- fucopyranosyl-23,28-dihydroxy-oleane-11, 13(18)-diene (1) and 3-O-α-l-rhamnopyranosyl-(1 → 4)-β -d-glucopyranosyl-(1 → 3)-[β -d-glucopyranosyl-(1 → 2)]-β -d-fucopyranosyl-16,23,28-trihydroxy-oleane-11,13(18)-diene (2) isolated from leaves of Buddleia scordioides Kunth (Loganiaceae) were studied for the effect on wound healing, using excision and incision wound modes. Significant increase in granulation tissue, tensile strength, hydroxyproline, total protein, and collagen contents was observed. There was significant reduction in the wound area measurement of the test group compared with that of controls. The efficacious prohealing effect may be due to increased collagen deposition as well as to better alignment and maturation.     

Wound Healing and Antioxidant Activity of Achyranthes aspera

Achyranthes aspera Linn (Amaranthaceae), commonly known as apamarga, is a commonly available plant in India. This plant has been used in the treatment of cuts by the people living in Tamil Nadu. The ethanol and aqueous extracts of leaves of Achyranthes aspera were prepared and its wound healing and antioxidant activity were evaluated. The wound healing activity was studied using two wound models, excision wound model and incision wound model. The free radical scavenging activity of the extracts was also assessed using two methods, DPPH radical scavenging activity, and superoxide scavenging activity. The extracts responded significantly in both the wound models tested. Also, the plant exhibited good antioxidant effect by preventing the formation of free radicals in the two models studied. Comparatively, the aqueous extract was found to be more effective. These findings could justify the inclusion of this plant in the management of cuts by the local people.     

Delivery of Therapeutics from Layer-by-Layer Electrospun Nanofiber Matrix for Wound Healing: An Update

Increasing incidences of chronic wounds urge the development of effective therapeutic wound treatment. As the conventional wound dressings are found not to comply with all the requirements of an ideal wound dressing, the development of alternative and effective dressings is demanded. Over the past few years, electrospun nanofiber has been recognized as a better system for wound dressing and hence has been studied extensively. Most of the electrospun nanofiber dressings were fabricated as single-layer structure mats. However, this design is less favorable for the effective healing of wounds mainly due to its burst release effect. To address this problem and to simulate the organized skin layer's structure and function, a multilayer structure of wound dressing had been proposed. This design enables a sustained release of the therapeutic agent(s), and more resembles the natural skin extracellular matrix. Multilayer structure is also referred to layer-by-layer (LbL), which has been established as an innovative method of drug incorporation and delivery, combines a high surface area of electrospun nanofibers with the multilayer structure mat. This review focuses on LbL multilayer electrospun nanofiber as a superior strategy in designing an optimal wound dressing.     

Understanding and Managing the Impact of HPMC Variability on Drug Release from Controlled Release Formulations

The purpose of this study is to identify critical physicochemical properties of hydroxypropyl methylcellulose (HPMC) that impact the dissolution of a controlled release tablet and develop a strategy to mitigate the HPMC lot-to-lot and vendor-to-vendor variability. A screening experiment was performed to evaluate the impacts of methoxy/hydroxypropyl substitutions, and viscosity on drug release. The chemical diversity of HPMC was explored by nuclear magnetic resonance (NMR), and the erosion rate of HPMC was investigated using various dissolution apparatuses. Statistical evaluation suggested that the hydroxypropyl content was the primary factor impacting the drug release. However, the statistical model prediction was not robust. NMR experiments suggested the existence of structural diversity of HPMC between lots and more significantly between vendors. Review of drug release from hydrophilic matrices indicated that erosion is a key aspect for both poorly soluble and soluble drugs. An erosion rate method was then developed, which enabled the establishment of a robust model and a meaningful HPMC specification. The study revealed that the overall substitution level is not the unique parameter that dictates its release-controlling properties. Fundamental principles of polymer chemistry and dissolution mechanisms are important in the development and manufacturing of hydrophilic matrices with consistent dissolution performance. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1664–1672, 2014     

壳聚糖喷雾剂促大鼠创伤及烫伤愈合作用的研究

摘 要 目的：探究自制壳聚糖喷雾剂对创伤及烫伤创面的促愈合作用。方法: 分别建立大鼠创伤和烫伤模型,将造模成功的SD大鼠随机分为实验组（壳聚糖喷雾剂组）、阳性对照组（立见护创液喷雾剂组）和模型对照组,每组10只。观察大鼠及伤口一般状况、存活率、愈合时间和愈合率。结果: 创伤实验中,实验组和阳性对照组的创面愈合时间和愈合率（第4,8,12天）与模型对照组比较差异均有统计学意义（P<0.05）,实验组和阳性对照组之间差异无统计学意义（P>0.05）。烫伤实验中,与模型对照组相比,实验组和阳性对照组的创面愈合时间差异有统计学意义（P<0.05）,第12,16天的愈合率差异有统计学意义（P<0.05）,而第4,8天的愈合率差异无统计学意义（P>0.05）。结论:自制壳聚糖喷雾剂对创伤及烫伤创面均具有一定的促愈合效果,在创伤中的促愈合效果优于烫伤,本研究为该制剂的进一步开发提供依据。     

保留灌肠促进痔术后创面愈合的临床观察

目的:观察庆大霉素 甲硝唑保留灌肠对混合痔外剥内扎术后创面愈合的影响.方法:100例混合痔分为治疗组50例,对照组50例,分别应用庆大霉素 甲硝唑17 mL保留灌肠和复方紫草油纱条换药,观察愈合情况.结果:创面愈合时间治疗组为9.5±1.8 d,对照组为15.6±3.7 d,治疗组明显缩短(P＜0.01);创面表皮生长速度,治疗组为6.1±0.5 mm·3d-1,对照组为3.0±0.5 mm·3d-1,治疗组明显增快(P＜0.01).两组均未见全身不适及局部反应.结论:保留灌肠可加速痔术后创面的愈合过程,减少患者痛苦,疗效确切安全.