Development of meloxicam-loaded electrospun polyvinyl alcohol mats as a transdermal therapeutic agent

This study reports on the use of electrospun polyvinyl alcohol (PVA) nanofiber mats loaded with meloxicam (MX) as a transdermal drug delivery system. The amounts of MX loaded in the base PVA solution (10% w/v solution) were 2.5, 5, 10 and 20% weight, based on the dry weight of PVA (% wt). The average diameters of these fibers ranged from 121-185 nm. In all concentrations of MX loaded in spun PVA fiber mats, an amorphous nanodispersion of MX with PVA was obtained. Both the degree of swelling and the weight loss of the electrospun PVA mats were greater than those of the as-cast PVA films. The tensile strength of the as-spun fiber mats was lower than that of the as-cast PVA films, but the strain at the maximum of the as-spun fiber mats was about six times higher than that of the as-cast PVA films. The skin permeation flux of the MX permeated from MX-loaded as-spun PVA were significantly higher than from MX-loaded as-cast PVA films, and increased when the MX content in both MX-loaded as-spun PVA and MX-loaded as-cast PVA films was increased. Our research suggests a potential use for MX-loaded electrospun PVA mats as a transdermal drug delivery system.     

Fabrication and properties of capsicum extract-loaded PVA and CA nanofiber patches

The aim of this study was to prepare, characterize and evaluate electrospun polyvinyl alcohol (PVA) and cellulose acetate (CA) nanofibers loaded with capsicum extract (CE) for use in topical skin treatments. CE, 0.5, 1 or 2 wt %, was loaded into PVA and CA electrospun fiber mats. Various properties of the CE-loaded fiber mats as well as release and skin permeation were investigated. The average diameters of these fibers ranged from 251–368?nm. The release rate of capsaicin from CE-loaded as-spun PVA was faster than that of the CA fiber mats and increased as the CE content in CE-loaded as-spun PVA and CA increased. The release kinetics of the CA and PVA fibers followed the Higuchi equation. The percentages of CE that permeated the shed snake skin with PVA and CA fiber mats containing 2 wt % CE after 24?h were 60% and 20%, respectively. The results suggest a potential use of PVA and CA nanofibers being used to control skin permeation of capsicum extract. Our research suggests the potential application of CE-loaded PVA electrospun mats as transdermal drug delivery systems.     

Vitamin-loaded electrospun cellulose acetate nanofiber mats as transdermal and dermal therapeutic agents of vitamin A acid and vitamin E.

The present contribution reports the use of mats of electrospun cellulose acetate (CA; acetyl content=39.8%; Mw=30,000 Da) nanofibers as carriers for delivery of the model vitamins, all-trans retinoic acid or vitamin A acid (Retin-A) and alpha-tocopherol or vitamin E (Vit-E). The amounts of Vit-E and Retin-A loaded in the base CA solution [17% w/v in 2:1 v/v acetone/N,N-dimethylacetamide (DMAc)] were 5 and 0.5 wt% (based on the weight of CA), respectively. Cross-sectionally round and smooth fibers were obtained. The average diameters of these fibers ranged between 247 and 265 nm. The total immersion of the vitamin-loaded as-spun CA fiber mats in the acetate buffer solutions containing either 0.5 vol % Tween 80 or 0.5 vol % Tween 80 and 10 vol % methanol was used to arrive at the cumulative release of the vitamins from the fiber mat samples. The same was also conducted on the vitamin-loaded solution-cast CA films for comparison. In most cases, the vitamin-loaded as-spun fiber mats exhibited a gradual and monotonous increase in the cumulative release of the vitamins over the test periods (i.e., 24 h for Vit-E-loaded samples and 6 h for Retin-A-loaded ones), while the corresponding as-cast films exhibited a burst release of the vitamins.     

Lysozyme-loaded, electrospun chitosan-based nanofiber mats for wound healing

In this study, a blend mixture of chitosan-ethylenediaminetetraacetic acid (CS 2 wt%-EDTA) at a weight ratio of 30/70 and polyvinyl alcohol (PVA) solution (10 wt%) was electrospun to produce fibrous mats with lysozyme (10, 20 and 30 wt%) used for wound healing. The morphology and diameter of the electrospun fiber mats with and without lysozyme were analyzed by scanning electron microscopy (SEM). The amount of lysozyme loaded in the nanofiber mats was measured by HPLC. The cell lysis activity of the lysozyme was investigated with Micrococcus lysodeikticus cells as a substrate. The wound healing activity was performed in vivo using male Wistar rats. The SEM images of all lysozyme-loaded fibers show a smooth fiber without beads with an average diameter of 143-209 nm. The amount of lysozyme loaded in the nanofiber mats was slightly decreased when the initial concentration of lysozyme was increased. The rapid lysozyme release from the nanofiber mats was obtained and is dependent on the lysozyme-loading amount. In animal wound healing, lysozyme loaded CS-EDTA nanofiber mats accelerated the rate of wound healing when compared to the controls (gauze). In conclusion, our experiments demonstrated that biomaterials composed of lysozyme loaded CS-EDTA nanofibers have a potential for wound healing.     

In vivo wound healing performance of drug loaded electrospun composite nanofibers transdermal patch

Acute injuries or wound is required the fast delivery of drug to control infections without any side effect. In this direction in the present investigation, antibiotic ciprofloxacin loaded hydrophilic biodegradable poly vinyl alcohol (PVA) and sodium alginate (NaAlg) electrospun composite nanofiber based transdermal patch was developed for local delivery of antibiotic drug. The antibiotic drug ciprofloxacin was loaded in it by active loading. The drug entrapped in the composite nanofibers was confirmed by the scanning electron microscopy and swelling behavior. The in vivo studies were carried on male rabbits by using the drug loaded and unloaded composite nanofibers transdermal patch and marketed one. It is observed that, in vitro activity provides a sustained and controlled release pattern of the drug from transdermal patch. The mechanism of drug release was also studied using different models. The nanofiber transdermal patch follows the Higuchi and Korsmeyer–Peppas model for drug release. The in vivo studies demonstrate that, wound healing takes place in less time as compared drug unloaded patch. Hydroxyproline produced in wound bed with time shows that it content is maximum in case drug loaded PAV-NaAlg patch. This demonstrates that wound healing rate is higher in case drug loaded PVA-NaAlg transdermal patch.     

Neomycin-loaded poly(styrene sulfonic acid-co-maleic acid) (PSSA-MA)/polyvinyl alcohol (PVA) ion exchange nanofibers for wound dressing materials

In this study, poly(styrene sulfonic acid-co-maleic acid) (PSSA-MA) blended with polyvinyl alcohol (PVA) was electrospun and then subjected to thermal crosslinking to produce PSSA-MA/PVA ion exchange nanofiber mats. The cationic drug neomycin (0.001, 0.01, and 0.1%, w/v) was loaded onto the cationic exchange fibers. The amount of neomycin loaded and released and the cytotoxicity of the fiber mats were analyzed. In vivo wound healing tests were also performed in Wistar rats. The results indicated that the diameters of the fibers were on the nanoscale (250 ± 21 nm). The ion exchange capacity (IEC) value and the percentage of water uptake were 2.19 ± 0.1 mequiv./g-dry fibers and 268 ± 15%, respectively. The loading capacity was increased upon increasing the neomycin concentration. An initial concentration of 0.1% (w/v) neomycin (F3) showed the highest loading capacity (65.7 mg/g-dry fibers). The neomycin-loaded nanofiber mats demonstrated satisfactory antibacterial activity against both Gram-positive and Gram-negative bacteria, and an in vivo wound healing test revealed that these mats performed better than gauze and blank nanofiber mats in decreasing acute wound size during the first week after tissue damage. In conclusion, the antibacterial neomycin-loaded PSSA-MA/PVA cationic exchange nanofiber mats have the potential for use as wound dressing materials.     

Electrospun fibers of acid-labile biodegradable polymers with acetal groups as potential drug carriers

The local delivery and controllable release profiles make electrospun ultrafine fibers as potential implantable drug carriers and functional coatings of medical devices. Till date there is no literature report on drug delivery from acid-labile electrospun fibers, whose degradation and drug release behaviors respond to the local pathological pH environment. Acid-labile groups have been incorporated into nonbiodegradable backbones as crosslinkers or linkers of the side chains. A novel strategy was developed in this study to synthesize acid-labile polymers by introducing acetal groups into biodegradable backbone of poly(dl-lactide)-poly(ethylene glycol). In vitro release study showed that the total amount of drug released from acid-labile polymeric fibers was accelerated on account of pH-induced structural and morphological changes of fibrous mats and the degradation of matrix polymers, and the burst release was significant higher for polymers with higher contents of acid-labile segments. During the investigational period, almost no molecular weight reduction and mass loss was detected in neutral buffer solutions, but the degradation was enhanced in acid buffers with a two-stage degradation profile. Surface erosion mechanism was initially detected for fibrous mats with distinct fiber morphologies, and bulk degradation was determined during the following incubation for polymeric films resulting from the morphological changes.     

Antitumor activity of electrospun polylactide nanofibers loaded with 5-fluorouracil and oxaliplatin against colorectal cancer

The purpose of this study was to evaluate both in vitro and in vivo anticancer activities against colorectal cancer (CRC) of electrospun polylactide (PLA) nanofibers loaded with 5-fluorouracil (5-Flu) and oxaliplatin. For in vitro evaluation, human CRC HCT8 cells were directly exposed to the drug-loaded fiber mats, followed with MTT and flow cytometry (FCM) assay. For in vivo evaluation, the drug-loaded fiber mats were locally implanted into mouse colorectal CT26 tumor-bearing mice, followed with histological analysis and detection of survival rate. The results showed that the drug-loaded fiber mats was similar to that of the combination of free 5-Flu and oxaliplatin in vitro cytotoxicity but was much superior to intravenous injection of free drug in vivo anticancer activities, presenting with suppressed tumor growth rate and prolonged survival time of mice. In conclusion, anticancer activities of 5-Flu and oxaliplatin against CRC can be significantly improved by using PLA electrospun nanofibers as local drug delivery system.     

Electrospun fiber mats containing shikonin and derivatives with potential biomedical applications

Alkannin, shikonin (A/S) and their derivatives are naturally occurring hydroxynaphthoquinones with a well-established spectrum of wound healing, antimicrobial, anti-inflammatory, antioxidant and antitumor activity. Clinical studies over the years revealed that A/S derivatives-based wound healing preparations (such as HELIXDERM(?)) are among a very small group of therapeutics that modulate both the inflammatory and proliferative phases of wound healing and present significant tissue regenerative activity. The purpose of the present work was to combine the biological properties of A/S and the advantages of electrospun meshes to prepare a potent topical/transdermal biomaterial for A/S. Four biocompatible polymers (cellulose acetate, poly(L-lactide), poly(lactide-co-glycolide) LA/GA:50/50 and 75/25) were used for the first time, to produce electrospun fiber mats containing either shikonin or A/S mixture in various amounts. Both drugs were effectively loaded into the above biomaterials. The incorporation of drugs did not considerably affect fibers morphology and their mean diameter size varied from 315 to 670 nm. High drug entrapment efficiencies (ranged from 74% to 95%) and appropriate release profiles were achieved, that render these fibers as potential A/S topical/transdermal wound healing dressings. Given the multifunctional activity of the natural products alkannins and shikonins, their consideration as bioactive constituents for tissue engineering scaffolds seems a promising strategy for repairing and regenerating tissues and mainly skin.     

Hybrid Electrospun Polycaprolactone Mats Consisting of Nanofibers and Microbeads for Extended Release of Dexamethasone

Purpose

We designed electrospun polycaprolactone mats consisting of nanofibers and microbeads for extended delivery of dexamethasone.

Methods

Thin flexible dexamethasone loaded polycaprolactone mats were prepared by electrospinning. The solvents, polymer loading, voltage and tip-to-collector distance were varied to explore the effects on microstructure of the mats. The microstructure was determined by scanning electron microscope imaging; drug transport was measured and modeled, and X-ray diffraction was used to gauge the crystallinity. Drug transport and X-ray diffraction studies were also conducted with a spin cast film for comparison.

Results

Thin mats, about 10 μm in thickness, were prepared by electrospinning. By controlling the voltage and tip-to-collector distance, we achieved a hybrid structure comprising of nanorods (nanofibers) and microbeads. The release profiles were fitted to the diffusion equation to obtain the diffusivities in the spheres and the rods. The diffusivity in the electrospun nanofibers was significantly lower compared to the casted films due to increased crystallinity, which was estimated from X-ray diffraction analysis. The electrospun hybrid mats sustained drug release for the desired duration of a month, in spite of the small thickness of about 10 μm. By comparison, a ten-fold thicker cast film sustains release for about the same duration suggesting about 100-fold decrease in diffusivity in the electrospun mats due to increased crystallinity.

Conclusions

Electrospun polycaprolactone mats are optimal for achieving long release durations due to increased crystallinity. Designing a hybrid structure by controlling the electrospinning parameters can be a useful approach to increase the release durations.

     

酮基布洛芬贴片的制备及体外渗透性研究

目的：观察环丙沙星治疗下呼吸道感染的疗效。方法：１００例患者（男性５２例,女性４８例,年龄（４５±８）ａ用药剂量为５００ｍｇ,每１２ｈ口服１次,疗程一般为７～２１ｄ。结果：临床总有效率为９２０％,细菌清除率为８７２％,对革兰氏阳性及阴性菌均有效,敏感菌百分率达８８５％,特别对铜绿假单胞菌感染也有较好的疗效。结论：环丙沙星治疗下呼吸道感染疗效满意,副作用少,是安全、方便、可靠的有效药物。     

褶合光谱法测定复方地塞米松滴眼液的含量

目的：制备酮基布洛芬凝胶贴片,并考察体外经皮渗透性。方法：以聚乙烯醇（ＰＶＡ）和甘油为载体,以尿素为促进剂。结果：药物经皮渗透符合零级动力学过程,贴片中尿素含量超过１０％时,有显著的透皮促进作用。结论：贴片制剂稳定,符合临床用药要求。     

Ultrafine PEG-PLA fibers loaded with both paclitaxel and doxorubicin hydrochloride and their in vitro cytotoxicity

By means of “emulsion-electrospinning”, both hydrophobic and hydrophilic drugs, paclitaxel (PTX) and doxorubicin hydrochloride (DOX), were successfully loaded into PEG-PLA nanofiber mats to realize multi-drug delivery. The release behaviors of both the drugs from the same fiber mats were ascribed to their solubility properties and distribution status in the fibers. Due to its high hydrophilicity, DOX was easy to diffuse out from the fibers, and its release rate was always faster than that of hydrophobic PTX. Moreover, the release rate of PTX was accelerated by DOX’s release from the same drug-loaded fibers. In vitro cytotoxicity against rat Glioma C6 cells indicated that the dual drug combination showed a higher inhibition and apoptosis against C6 cells than a single drug-loaded system, which suggests the promise for multi-drug delivery on combination therapy.     

Fast-Acting Clotrimazole Composited PVP/HPβCD Nanofibers for Oral Candidiasis Application

Purpose

This study investigates fabrication of clotrimazole (CZ)-composited electrospun Polyvinylpyrrolidone/Hydroxypropyl-β-cyclodextrin (PVP/HPβCD) blended nanofiber mats for oral candidiasis applications.

Methods

PVP/HPβCD blended nanofiber mats containing clotrimazole were electrospun and characterized using SEM, DSC and XRPD. The solvent system ethanol: water: benzyl alcohol (EtOH:H₂O:BzOH) with a 70:20:10 ratio was optimal for the electrospinning process. Various amounts of CZ were loaded into the nanofiber mats. The nanofiber mats was further investigated for drug release, antifungal activity and cytotoxicity.

Results

The fiber diameters in the mats were in the nanometer range. The DSC and XRPD revealed a molecular dispersion of amorphous CZ in the nanofiber mats. The loading capacity increased when CZ content was raised. A fast dissolved and released of CZ from the nanofibers mat was achieved. The ability of the CZ-loaded nanofiber mats to kill the Candida depended on the amount of CZ in the mats; moreover, the CZ-loaded nanofibers killed the Candida significantly faster than the CZ powder and lozenges with low cytotoxicity.

Conclusions

CZ-loaded nanofiber mats were successfully electrospun. They exhibited rapid antifungal activity in vitro relative to CZ powder and lozenges. Further in vivo studies are needed to investigate for their application in oral candidiasis.     

Formulation and evaluation of meloxicam niosomes as vesicular carriers for enhanced skin delivery

Context: Skin delivery of Meloxicam (MX) offers several advantages over the oral route which is associated with potential side effects.

Objectives: The aim of this study was to develop transdermal MX in niosomes.Materials and Methods: Vesicles prepared by thin film hydration method were characterized and the acute anti-inflammatory activity of 0.5% MX niosomal hydrogel was evaluated using carrageenan induced rat paw edema method. Results: The results revealed that niosomes prepared from span 60 and cholesterol at 6:4 molar ratio using 20?mg of MX were of the highest entrapment efficiency (> 55%) and with particle size (187.3?nm). There was a marked increase in the percentage inhibition of edema in animals treated with MX vesicular gel compared to those treated with free MX and piroxicam gels.

Discussion: There was an inverse proportionality between vesicle size and cholesterol content. With increased cholesterol molar ratio the bilayer stability increased and permeability decreased leading to efficiently trapping the MX. In contrast, higher amounts of cholesterol may compete with the drug for packing space within the bilayer. The inhibitory effect of MX niosomal gel may be attributed to its superior skin permeation.

Conclusions: The results suggest that niosomes may be promising vehicles for transdermal delivery of MX.     

Electrospun Gelatin Fiber Mats Mixed With C.carandas Extract and its Enhanced Stability and Bioactivity

Crude C. carandas fruits ethanol extract (CCE) constituents important bioactive compounds such as phenolics, flavonoids, and vitamin C. Its biological activities include anti-inflammatory, antioxidant, antibacterial, etc. The present work was carried out to study the optimal conditions for fabricating electrospun gelatin fiber mats (GFM) loaded with CCE (CCE-GFM) and to evaluate the release capacity and stability of these bioactive compounds loaded into GFM. The optimal conditions for electrospinning GFM were the electrospinning 30% (w/v) gelatin solution prepared in 25% (v/v) ethanol solution containing 30% (v/v) acetic acid, under the fixed electrostatic field strength of 20 kV and at a distance between noodle tip and ground of 15 cm. The feed rate of an electrospinning solution was 1.5 mL/h. The electrospun gelatin fibers were smooth and continuous under the optimized electrospinning conditions, with an average diameter of 235.69 ± 10.45 nm. Additionally, at the loading of 15% (w/w) CCE in GFM, CCE-GFM exhibited the highest DPPH radical scavenging activity with 88.22 ± 2.62% and the highest tyrosinase inhibitory activity with 38.17 ± 1.86%. Compared with free CCE, CCE-GFM was more thermally stable upon the heating and cooling cycle testing. CCE-GFM had the percent reductions in total contents of phenolics, flavonoids and vitamin C togethering with the percent reductions of DPPH scavenging and anti-tyrosinase activities slower than pure CCE had. Furthermore, the drug release efficiency from CCE-GFM of 15% (w/w) CCE loading that was tested using modified Franz diffusion cell in an acetate buffer solution of pH 5.5 was 30%. CCE-GFM has shown the potential to utilize a facial mask sheet containing CCE valuable in high antioxidant activity for cosmetic applications.     

曲尼司特巴布剂的研制及释放度测定

目的:制备曲尼司特巴布剂并研究其体外释药性能.方法:以水溶性高分子材料为主要基质,以巴布剂基质的成型时间为指标,考察影响巴布剂物理性状和影响因素;进行体外释放度的测定,研究巴布剂的透皮释放行为.结果:巴布剂最佳处方为:曲尼司特 0.5 g,聚乙烯醇 6 g,水溶性高分子材料 25 g,甘油 5 g,丙二醇 5 g,氮酮 5 g,蒸馏水加至 150 g;4天药物释放率大于80%.结论:曲尼司特巴布剂含水量高,皮肤水合效果好,无刺激性;符合皮肤缓释型透皮给药系统的要求.     

Formulation and characterization of acetaminophen nanoparticles in orally disintegrating films

Abstract

The purpose of this study was to prepare orally disintegrating films containing nanoparticles loaded with acetaminophen. Nanoparticles were prepared by the emulsion-solvent evaporation method where acetone phase containing acetaminophen and poly(lactide-co-glycolide acid) (PLGA) was added to water phase containing hydroxypropyl methyl cellulose, poly ethylene glycol, polyvinyl alcohol (PVA) and aspartame in a rate of 1.5 drop?s^?1 and agitated at 1200?rpm. The size, polydispersity index (PI) and drug entrapment (DE) were measured. The emulsions were cast to form films, which were evaluated physico-mechanically. The effect of different degrees of hydrolization of PVA and polymerization of PLGA and the effect of different ratios of PVA to PLGA was studied. Films with acceptable physico-mechanical properties were further studied. The size and PI of the nanoparticles was dependent on PVA hydrolization, PLGA polymerization and the ratio of PVA to PLGA. All films disintegrated in less than one minute, but acetaminophen was not free in the dissolution media even after six days. These results may indicate that although the nanoparticles released from the films immediately when impressed in solution the drug is sustained in the nanoparticles for longer time, which is to be clarified in future work.     

难溶性多西紫杉醇的溶解微针制备及体外评价

目的:制备一种用于透皮给药的负载多西紫杉醇(DTX)的溶解微针,并进行体外评价。方法:考察不同材料及配方制备DTX溶解微针(DTX-MN),通过外观和力学性能指标对微针进行表征,测定微针针头载药量。使用猪皮肤考察微针溶解性能。剥离小鼠腹部皮肤,进行体外透皮吸收研究,初步考察DTX-MN给药后的皮肤药代动力学。结果:成功制备了针头完整、力学性能良好的DTX-MN,最佳工艺得到的微针针头载药量为(14.81±4.20)μg (n=5),微针能完整插入皮肤穿透角质层屏障,且在10 min内完全溶解。体外透皮实验显示,DTX-MN的初始透皮速率和累积透皮通量都高于药物溶液组,相比溶液组,DTX-MN在24 h后累积渗透量提高了3.27倍,其释放机制符合Fickian扩散。结论:制备的DTX-MN有良好的穿刺皮肤的性能,能够显著促进DTX的透皮递送,该类微针有望促进DTX的浅表皮肤递送,具有潜在的临床应用价值。     

Ion-exchange and iontophoresis-controlled delivery of apomorphine

The objective of this study was to test a drug delivery system that combines iontophoresis and cation-exchange fibers as drug matrices for the controlled transdermal delivery of antiparkinsonian drug apomorphine. Positively charged apomorphine was bound to the ion-exchange groups of the cation-exchange fibers until it was released by mobile counter-ions in the external solution. The release of the drug was controlled by modifying either the fiber type or the ionic composition of the external solution. Due to high affinity of apomorphine toward the ion-exchanger, a clear reduction in the in vitro transdermal fluxes from the fibers was observed compared to the respective fluxes from apomorphine solutions. Changes in the ionic composition of the donor formulations affected both the release and iontophoretic flux of the drug. Upon the application of higher co-ion concentrations or co-ions of higher valence in the donor formulation, the release from the fibers was enhanced, but the iontophoretic steady-state flux was decreased. Overall, the present study has demonstrated a promising approach using ion-exchange fibers for controlling the release and iontophoretic transdermal delivery of apomorphine.