Discrimination of normal and cancerous human skin tissues based on laser-induced spectral shift fluorescence microscopy.

A homemade spectral shift fluorescence microscope (SSFM) is coupled with a spectrometer to record the spectral images of specimens based on the emission wavelength. Here a reliable diagnosis of neoplasia is achieved according to the spectral fluorescence properties of ex-vivo skin tissues after rhodamine6G (Rd6G) staining. It is shown that certain spectral shifts occur for nonmelanoma/melanoma lesions against normal/benign nevus, leading to spectral micrographs. In fact, there is a strong correlation between the emission wavelength and the sort of skin lesions, mainly due to the Rd6G interaction with the mitochondria of cancerous cells. The normal tissues generally enjoy a significant red shift regarding the laser line (37 nm). Conversely, plenty of fluorophores are conjugated to unhealthy cells giving rise to a relative blue shift i.e., typically SCC (6 nm), BCC (14 nm), and melanoma (19 nm) against healthy tissues. In other words, the redshift takes place with respect to the excitation wavelength i.e., melanoma (18 nm), BCC (23 nm), and SCC (31 nm) with respect to the laser line. Consequently, three data sets are available in the form of micrographs, addressing pixel-by-pixel signal intensity, emission wavelength, and fluorophore concentration of specimens for prompt diagnosis.

Decreased recurrence of symptoms in oral lichen planus with intralesional injection of hyaluronic acid and triamcinolone.

Oral lichen planus (OLP) is a chronic non-infectious, inflammatory, immunological disease. In contrast to skin lesions, which are often self-limiting, oral lesions rarely heal on their own and can be resistant to local and systemic treatments. In this clinical trial, hyaluronic acid (HA) was mixed with triamcinolone for intralesional injection to reduce side effects in the treatment of OLP. This randomized clinical trial with a split-mouth design was performed on 28 patients with OLP. The mouth was divided randomly into two sides: a test side, which received HA combined with triamcinolone, and a control side, which received triamcinolone alone. The rate of symptom recurrence was 74.1% on the control side and 11.1% on the test side (significant difference, P<0.01). Pain scores did not differ between the two groups when assessed after 2 weeks. The group treated with a combination of HA and triamcinolone experienced a significantly better resolution of lesions and symptoms. Considering the role of HA in tissue healing and in regulating inflammatory responses, as well as its antioxidant and hydration properties, it appears that HA could be effective in improving of OLP and decreasing the rate of symptom recurrence.

Synergistic performance of triggered drug release and photothermal therapy of MCF7 cells based on laser activated PEGylated GO + DOX.

Graphene oxide is used as a singular 2D nano-carrier in cancer therapy. Here, graphene oxide is used as a hybrid chemo-drug graphene oxide (GO) + doxorubicin (DOX), mainly due to its unique chemical and optical properties. The laser triggers GO + DOX for selective drug delivery to optimize the drug release. The characterization of GO is investigated in terms of laser properties at 808 nm. Furthermore, the laser activates GO + DOX compounds to treat MCF7 cancerous cells. The drug release strongly depends on the temperature rise that mainly effects on the viability of the cancerous cells of interest. DOX simultaneously acts as a chemo-drug and as an optical fluorescent agent, whereas GO performs as an efficient photothermal nano-carrier. In fact, the GO-DOX hybrid drug demonstrates multifunctional during malignant cell treatment. We have shown that the laser heating of GO enhances the release percentage up to a treatment yield of 90%. This arises from the synergistic nature of DOX and GO compounds in simultaneous chemo/photo thermal therapy. Furthermore, the fluorescence property of DOX is used to assess the GO uptake using confocal microscope imaging.

Oral delivery of nanoparticles containing anticancer SN38 and hSET1 antisense for dual therapy of colon cancer.

An oral delivery system intended for treatment of colon cancer in HT29 cancerous cells was investigated by encapsulating hSET1 antisense and SN38 anticancer in nanoparticles based on cysteine trimethyl chitosan (cysTMC) and carboxymethyl dextran (CMD). Studies have shown hSET1 as the main type of histone methyltransferase (HMT) complex, is significantly overexpressed in malignant cells. In this study, hSET1 antisense was employed to inhibit gene expression. Additionally, SN38 was incorporated into nanoparticles to enhance the efficiency of the system by inhibition of topoisomerase 1. CysTMC was synthetized and characterized by (1)H NMR and FTIR. Nanoparticles were prepared through complexation of CMD and cysTMC. Particle size and surface charge was 100-150 nm and 17-21 mV respectively with drug content of around 2.6%. Gel electrophoresis assay proved the stability of antisense in simulated gastric and intestinal fluids. Nanoparticles showed high mucoadhesion and glutathione responsive release. Cellular uptake was observed by confocal microscopy and quantified by flow cytometry. Cytotoxicity of NPs was assessed using MTT assay. Results showed hSET1/SN38 nanoparticles had significantly higher cytotoxicity against HT29 cells compared with nanoparticles containing SN38, free SN38 or naked hSET1. Therefore, present system could be considered an effective combination therapy of highly hydrophobic SN38 and hSET1.

Enhanced Cellular Cytotoxicity and Antibacterial Activity of 18-ß-Glycyrrhetinic Acid by Albumin-conjugated PLGA Nanoparticles.

The aim of the present work was to encapsulate 18-ß-Glycyrrhetinic acid (GLA) in albumin conjugated poly(lactide-co-glycolide) (PLGA) nanoparticles by a modified nanoprecipitation method. Nanoparticles (NPs) were prepared by different drug to polymer ratios, human serum albumin (HSA) content, dithiothreitol (as producer of free thiol groups) content, and acetone (as non-solvent in nanoprecipitation). NPs with a size ranging from 126 to 174 nm were achieved. The highest entrapment efficiency (89.4±4.2%) was achieved when the ratio of drug to polymer was 1:4. The zeta potential of NPs was fairly negative (-8 to -12). Fourier transform infrared spectroscopy and differential scanning calorimetry proved the conjugation of HSA to PLGA NPs. In vitro release profile of NPs showed 2 phases: an initial burst for 4 h (34-49%) followed by a slow release pattern up to the end. The antibacterial effects of NPs against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa were studied by microdilution method. The GLA-loaded NPs showed more antibacterial effect than pure GLA (2-4 times). The anticancer MTT test revealed that GLA-loaded NPs were approximately 9 times more effective than pure GLA in Hep G2 cells.

MUC1 aptamer conjugated to chitosan nanoparticles, an efficient targeted carrier designed for anticancer SN38 delivery.

Molecularly targeted therapy is of great interest for diagnosis and treatment of cancerous cells due to its low toxicity for normal cells. In this study, chitosan was utilized as a promising carrier for delivery, and aptamer (Apt) was employed for active targeting of SN38 to colon cancer. SN38 cannot be used clinically due to its poor solubility and high toxicity. Developing nanoparticles (NPs) of drug-polymer conjugates can be a good candidate for overcoming such problems. N-Carboxyethyl chitosan ester (CS-EA) was synthesized as an intermediate for conjugation of SN38 to chitosan. MUC1 DNA aptamer with 5'-NH2 functional group was conjugated to the self-assembled conjugate as a targeting agent. Prepared NPs had smooth and spherical morphology with 200 nm particle size. Conjugation of aptamer was confirmed by gel electrophoresis. In vitro cytotoxicity of NPs was assessed by HT-29 as MUC1 positive cell line through MTT assay. Aptamer conjugated NPs (Apt NPs) were more toxic than non-targeted NPs, however they were as toxic as free drug. Cellular uptake and targeting ability of prepared NPs were also confirmed via confocal microscopy. As a conclusion, prepared CS-SN38-Apt NPs can increase efficacy of drug SN38 through increasing solubility and specific delivery to the target tissue.

Biodistribution of amikacin solid lipid nanoparticles after pulmonary delivery.

The main purpose of the present work was studying the biodistribution of amikacin solid lipid nanoparticles (SLNs) after pulmonary delivery to increase its concentration in the lungs for treatment of cystic fibrosis lung infections and also providing a new method for clinical application of amikacin. To achieve this aim, (99m)Tc labelled amikacin was loaded in cholesterol SLNs and after in vitro optimization, the desired SLNs and free drug were administered through pulmonary and i.v. routes to male rats and qualitative and biodistribution studies were done. Results showed that pulmonary delivery of SLNs of amikacin by microsprayer caused higher drug concentration in lungs than kidneys while i.v. administration of free drug caused reverse conditions. It seems that pulmonary delivery of SLNs may improve patients' compliance due to reduction of drug side effects in kidneys and elongation of drug dosing intervals due to the sustained drug release from SLNs.

Overcoming therapeutic obstacles in inflammatory bowel diseases: a comprehensive review on novel drug delivery strategies.

Inflammatory bowel diseases (IBDs) are a group of debilitating inflammatory complications specially inflicting colonic tissue in which full long term remission with current standardized treatments is yet intangible. Therapeutic side effects and efficacy considerations necessitate the development of more effective systems which lower the required drug doses, reduce systemic adverse effects and deliver the drug specifically to the desired site of action in colon. The large surface area in large intestine is suitable for drug absorption but the primary approaches to treatment depend on the gastrointestinal (GI) condition and its movements. Hereafter, there are novel GI-independent targeted drug delivery systems or therapeutic approaches, including micro- and nanoparticles that have been developed for IBD treatment and have the potential to overcome some of the current drawbacks of conventional IBD therapy. This review provides broad but concise information over the arena of the evolving systems aimed at different targets involved in IBD which are being studied in animal or in vitro models of this complication, while comparing these to conventional treatments. It further discusses important pros and cons of therapeutic approaches against IBD while helping to better understand and evaluate the future impact of novel drug delivery systems on human IBD and assisting in focusing the future research in this topic, on strategies which could provide maximum remission in IBD patients.

A review of polysaccharide cytotoxic drug conjugates for cancer therapy.

The most considerable challenges facing effective cancer therapy are systemic toxicity of cytotoxic drugs, their lack of tumor localizing and an even distribution throughout the whole body. Besides, short half-lives and undesirable pharmacokinetics are among the other drawbacks that inhibit effective cancer chemotherapy. Conjugation of low molecular weight drugs to polysaccharides has been used as a way to address these problems. This review will focus on polysaccharide drug conjugates and will provide an overview on various conjugation studies which have been accomplished for these carriers with cytotoxic drugs. Although a wide variety of anticancer agents including some toxins have been the subject of conjugation techniques, in this review, low molecular weight cytotoxic drugs conjugated covalently to the carriers are considered.

Formulation and evaluation of an in situ gel forming system for controlled delivery of triptorelin acetate.

The novel physical hydrogels composed of chitosan or its water soluble derivatives such as carboxymethyl chitosan (CMCh) and sodium carboxymethyl chitosan (NaCMCh) and opened ring polyvinyl pyrrolidone (OP-PVP) were used as a controlled delivery system for triptorelin acetate, a luteinizing-releasing hormone agonist. The in situ gel forming system designed according to physical interactions such as chains entanglements and hydrophilic attractions especially h-bonds of chitosan and/or NaCMCh and OR-PVP. In order to increase in situ gel forming rate the chitosan microspheres prepared through spray drying technique. The chitosan or NaCMCh/OR-PVP blends prepared at different ratios (0.05, 0.10, 0.12, 0.16, 0.20 and 0.24) and suspended in sesame oil as non-aqueous vehicle at different solid content (10-30%). The suitable ratio of polymers with faster in situ gel forming rate was selected for in vivo studies. The gel formation and drug release from the system was evaluated both in vitro and in vivo. In vitro and in vivo results were compared with Diphereline SR 3.75mg, a commercially available controlled delivery system of triptorelin. In vitro release studies showed a sustained release profile for about 192h with first order kinetics. In vivo studies on male rats by determination of serum testosterone were confirmed the acceptable performance of in situ gel forming system compared with Diphereline SR in decreasing the serum testosterone level for 35days, demonstrating the potential of the novel in situ gel forming system for controlled delivery of peptides.

Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents.

The effectiveness of anticancer agents may be hindered by low solubility in water, poor permeability, and high efflux from cells. Nanomaterials have been used to enable drug delivery with lower toxicity to healthy cells and enhanced drug delivery to tumor cells. Different nanoparticles have been developed using different polymers with or without surface modification to target tumor cells both passively and/or actively. Polylactide-co-glycolide (PLGA), a biodegradable polyester approved for human use, has been used extensively. Here we report on recent developments concerning PLGA nanoparticles prepared for cancer treatment. We review the methods used for the preparation and characterization of PLGA nanoparticles and their applications in the delivery of a number of active agents. Increasing experience in the field of preparation, characterization, and in vivo application of PLGA nanoparticles has provided the necessary momentum for promising future use of these agents in cancer treatment, with higher efficacy and fewer side effects.

Increased paclitaxel cytotoxicity against cancer cell lines using a novel functionalized carbon nanotube.

Potential applications of carbon nanotubes have attracted many researchers in the field of drug delivery systems. In this study, multiwalled carbon nanotubes (MWNTs) were first functionalized using hyperbranched poly citric acid (PCA) to improve their hydrophilicity and functionality. Then, paclitaxel (PTX), a potent anticancer agent, was conjugated to the carboxyl functional groups of poly citric acid via a cleavable ester bond to obtain a MWNT-g-PCA-PTX conjugate. Drug content of the conjugate was about 38% (w/w). The particle size of MWNT-g-PCA and MWNT-g-PCA-PTX was approximately 125 and 200 nm, respectively. Atomic force microscopy and transmission electron microscopy images showed a curved shape for MWNT-g-PCA and MWNT-g-PCA-PTX, which was in contrast with the straight or linear conformation expected from carbon nanotubes. It seems that the high hydrophilicity of poly citric acid and high hydrophobicity of MWNTs led to conformational changes from a linear state to a curved state. Paclitaxel can be released from the MWNT-g-PCA-PTX conjugates faster at pH 6.8 and 5.0 than at pH 7.4, which was suitable for the release of the drug in tumor tissues and tumor cells. In vitro cytotoxicity studies were evaluated in the A549 and SKOV3 cell lines. MWNT-g-PCA had an insignificant cytotoxic effect on both cell lines. MWNT-g-PCA-PTX had more of a cytotoxic effect than the free drug over a shorter incubation time (eg, 24 hours versus 48 hours), which suggests improved cell penetration of MWNT-g-PCA-PTX. Therefore, paclitaxel conjugated to MWNT-g-PCA is promising for cancer therapeutics.

Preparation and evaluation of poly (caprolactone fumarate) nanoparticles containing doxorubicin HCI.

BACKGROUND AND THE PURPOSE OF THE STUDY: Biodegradable Poly(caprolactone fumarate) (PCLF) has been used as bioresorbable sutures. In this study, doxorubicin HCl (Dox) loaded PCLF nanoparticles were prepared and characterized. MATERIAL AND METHODS: PCLFs were synthesized by polycondensation of PCL diols (Mws of 530, 1250 and 2000) with fumaryl chloride. The degradation of PCLF in NaOH, water and phosphate buffer saline (PBS), was determined in terms of changes in Mw. Nanoparticles (NPs) were prepared by two methods. In microemulsion polymerization method, dichloromethane containing PCLF and photoinitiator were combined with the water containing surfactants and then the mixture was placed under light for crosslinking. In nanoprecipitation method, the organic solvent containing PCLF was poured into the stirring water. The effect of several variables including concentration of PCLF, polyvinyl alcohol (PVA), Dox and Trypan blue (Trb) and the Mw of PCLF and PVA on NP size and loading were evaluated. RESULT: PCLF 530, 1250 and 2000 in PBS or water were not degraded over 28 days. Nanoprecipitaion method gave spherical (revealed by SEM images) stable NPs of about 225 with narrow size distribution and a zeta potential of -43 mV. The size of NP increased significantly by increase in Mw or concentration of PCLF. Although PVA was not necessary for formation of NPs, but it decreased with NP size. Dox loading and EE were 2.5-6.8% and 15-20%, respectively. Increasing the drug concentration increased the drug loading (DL) and NP size. The entrapment efficiency (EE) for Trb ranged from 1% for PCLF530 to 6% for PCLF2000. An increase in PCLF concentration resulted in an increase in EE. Dox and Trb release showed a burst followed by 80% and 78% release during 3 and 4 days respectively. CONCLUSION: PCLF possessed suitable characteristics for preparation of nanoparticulate drug delivery system such as desired NP size, stability and degradation time. Although PCLF530 NPs were the smallest, but their DL were lower than PCLF1250 and 2000 NPs.

Core shell methyl methacrylate chitosan nanoparticles: In vitro mucoadhesion and complement activation.

BACKGROUND AND THE PURPOSE OF THE STUDY: Studies show that chitosan nanoparticles increase mucoadhesivity and penetration of large molecules across mucosal surface. The aim of the present study was to investigate the use of thiolated chitosan in the development of polysaccharide-coated nanoparticles in order to confer specific functionality to the system. METHODS: Methyl methacrylate nanoparticles were coated with thiolated chitosan using a radical polymerization method. Thiolation was carried out using glutathione (GSH) to improve mucoadhesivity and permeation enhancing properties of chitosan. Mucoadhesion studies were carried out by calculating the amount of mucin adsorbed on nanoparticles in a specific period of time. Complement consumption was assessed in human serum (HS) by measurement of the hemolytic capacity of the complement system after contact with nanoparticles. RESULTS: The FT-IR and (1)HNMR spectra both confirmed the synthesis and showed the conjugation of thiolated chitosan to methyl methacrylate (MMA) homopolymer. Nanoparticles were spherical having a mean diameter within the range of about 334-650 nm and their positive zeta potential values indicated the presence of the cationic polysaccharide at the nanoparticle surface. Increasing the amount of thiolated chitosan led to mucoadhesivity and complement activation. However there was not dose dependent correlation between these phenomenons and the absence of thiolated chitosan led to particles with larger size, and without ability to activate complement process. MAJOR CONCLUSION: It can be concluded that nanoparticles could be used for the mucosal delivery of peptides and proteins. Results show that the thiolated chitosan had higher mucoadhesion and complement activation than unmodified chitosan.

Preparation and comparison of chitosan nanoparticles with different degrees of glutathione thiolation.

BACKGROUND: Chitosan has gained considerable attentions as a biocompatible carrier to improve delivery of active agents. Application of this vehicle in the form of nanoparticle could profit advantages of nanotechnology to increase efficacy of active agents. The purpose of this study was to provide detailed information about chitosan-glutathione (Cht-GSH)nanoparticles which are gaining popularity because of their high mucoadhesive and extended drug release properties. METHODS: Depolymerization of chitosan was carried out using sodium nitrite method.Glutathione was covalently attached to chitosan and the solubility of the resulting conjugates was evaluated. Nanoparticles were prepared by ionic gelation method and then the effect of glutathione immobilization on properties of nanoparticles was investigated. RESULTS: Thiolation efficiency was higher in lower molecular weight chitosan polymers compared to unmodified chitosan nanoparticles. Cht-GSH conjugates of the same molecular weight but with different degrees of thiolation had the same hydrodynamic diameter (995± nm) and surface charge (102± mV) as unmodified chitosan, but comprised of a denser network structure and lower concentration. Cht-GSH nanoparticles also exhibited greater mucoadhesive strength which was less affected by ionic strength and pH of the environment. CONCLUSION: Thiolation improves the solubility of chitosan without any significant changes in size and charge of nanoparticles, but affects the nanogel structure.

Ex vivo evaluation of insulin nanoparticles using chitosan and arabic gum.

Polymeric delivery systems based on nanoparticles have emerged as a promising approach for peroral insulin delivery. The aim of the present study was to investigate the release of insulin nanoparticulate systems and ex vivo studies. The nanoparticles were prepared by the ion gelation method. Particle size distribution, zeta potential, and polydispersity index of the nanoparticles were determined. It was found that the nanoparticles carried positive charges and showed a size distribution in the range of 170-200 nm. The electrostatic interactions between the positively charged group of chitosan and negatively charged groups of Arabic gum play an important role in the association efficiency of insulin in nanoparticles. In vitro insulin release studies showed an initial burst followed by a slow release of insulin. The mucoadhesion of the nanosystem was evaluated using excised rat jejunum. Ex vivo studies have shown a significant increase in absorption of insulin in the presence of chitosan nanoparticles in comparison with free insulin.

Thiolated chitosan nanoparticles as an oral delivery system for Amikacin: in vitro and ex vivo evaluations.

The purpose of this study was the synthesis of two thiol conjugated Chitosan polymers, and evaluation of the potential of Thiomer nanoparticle formulation as a carrier for oral delivery system. Mediated by EDAC (Ethylene-3-(3-di-methylaminopropyl)-carbodiimide), either N-acetyl Cysteine (NAC) or N-acetyl D-penicillamine (NAP) were covalently attached to Chitosan. The success of the synthesis was demonstrated by comparing FTIR spectra. Iodometric titration demonstrated that depending on the pH value of the synthesis medium, the Thiomers display 250 +/- 30 microMol and 300 +/- 20 microMol thiol groups per gram of polymer respectively. The interaction between mucin and Thiomers, compared to mucin and Chitosan was studied for assessment of mucoadhesion properties of synthesized polymers. This interaction was determined by the measurement of the amount of mucin adsorbed on Chitosan and the conjugated polymers. Rotating cylinder method demonstrated an average of 20 times improvement in mucoadhesion of Thiomers compared to the unmodified polymer. Chitosan and Thiomer nanoparticles were formulated by two methods; TPP and Sodium Sulfate gelation. SEM micrographs and data achieved by a Malvern nano/zetasizer show nanoparticles formed by TPP gelation have a mean size of 150 +/- 15 nm compared to 300 +/- 25 nm sized nanoparticles obtained by Sodium sulfate gelation. TPP gelation yields smaller, more spherical shaped nanoparticles with a smaller range of size distribution. Amikacin loaded nanoparticles with an average size of 280 nm were prepared by TPP gelation in which disulfide bond formation was achieved by a time dependent oxidation process. In vitro studies were carried out; a recovery rate of 33% and a drug entrapment of 25% were achieved. The amount of release was determined during 18 hr in a carefully prepared media. The permeation time across a biological membrane was observed to be about 150 minutes. Microbiological tests were carried out on two microorganisms; Pseudomona aeruginosa and Staphylococcus aureus to further confirm the amount of Amikacin inside drug loaded nanoparticles.

Preparation and characterization of poly lactide-co-glycolide nanoparticles of SN-38.

SN-38 (7-ethyl-10-hydroxycamptothecin) is the active metabolite of irinotecan (CPT-11), which is 100-1000-fold more cytotoxic than irinotecan. Nonetheless, the extreme hydrophobicity of SN-38 has prevented its clinical use. SN-38 is poorly soluble in aqueous solutions, and it is practically insoluble in most physiologically compatible and pharmaceutically acceptable solvents. One way of improving the solubility and stability of SN-38 is to formulate the drug into nanoparticles. Incorporation of cytotoxic agents into nanoparticles has also shown increased toxicity. In this study, poly lactide-co-glycolide was used for the preparation of nanoparticles of SN-38. The nanoparticles were fabricated by an emulsification/solvent evaporation method. The effect of several variables on nanoparticle characteristics was evaluated, including the ratio of drug-polymer, the amount of the poly vinyl alcohol as surfactant, and the internal phase volume/composition. The SN-38 encapsulation efficiency and the particle size distribution were optimized by varying these parameters. Nanoparticles were spherical with a relatively mono-dispersed size distribution. As the ratio of acetone to dichloromethane increased, a considerable decrease in the particle size of nanoparticles was achieved. The encapsulation efficiency of all samples was more than 80%. Changing the poly vinyl alcohol concentration in the external phase had some effects on size and morphology and encapsulation efficiency. It was shown that SN-38 nanoparticles are considerably stable in a long-term stability study.

Temperature modulated drug permeation through liquid crystal embedded cellulose membranes.

Stimuli-sensitive membranes may act as "on-off switches" or "permeability valves", producing patterns of pulsatile release, where the period and rate of mass transfer can be controlled by external or environmental triggers. In this study, cellulose nitrate (CN) and cellulose acetate (CA) monolayer membranes containing thermotropic liquid crystals (LC) were developed as thermoresponsive barriers for drug permeation. A low molecular thermotropic LC, n-heptyl-cyanobiphenyl (K21), with nematic to isotropic phase transition temperature (T(n-i)) of 41.5 degrees C was chosen to modulate drug permeation. Methimazole and paracetamol as hydrophilic and hydrophobic drug models were used, respectively. It was found that upon changing the temperature of the system around the T(n-i), both cellulose membranes without LC showed no temperature sensitivity to drug permeation, whereas the results for LC entrapped membranes exhibited a distinct jump in permeability when temperature was raised to above the T(n-i) of the liquid crystal for both drug models. On the other hand, drug permeation through these LC embedded membranes can be thermally modulated. Thermoresponsive drug permeation through the membranes was reversible, reproducible and followed zero order kinetics. Liquid crystal embedded cellulose acetate membranes showed more temperature sensitivity than liquid crystal embedded cellulose nitrate membranes, apparently due to higher LC loading in their porous matrix compared to CN membranes. The pattern of on-off permeation through LC embedded membranes was more distinguished for methimazole compared to that of paracetamol, seemingly due to its lower molecular weight.

Two statistical methods for resolving healthy individuals and those with congestive heart failure based on extended self-similarity and a recursive method.

In this paper we introduce two methods for measuring irregularities in human heartbeat time series (HHTS). First we consider the multi-fractal structure of HHTS to distinguish healthy individuals and from those with congestive heart failure. In this way we modify the Extended Self-Similarity (ESS) method and apply it to HHTS. Our second approach is based on the recursive method, which we use to predict the duration of the next heartbeat by considering a few previous ones. We use standard physiological data and show that these approaches lead to very satisfactory methods to resolve the healthy and CHF individuals. These methods can be used potentially in portable electronic heart alarm systems.