Progresses and perspectives on natural polysaccharide based hydrogels for repair of infarcted myocardium.

Myocardial infarction (MI) is serious health threat and impairs the quality of life. It is a major causative factor of morbidity and mortality. MI leads to the necrosis of cardio-myocytes, cardiac remodelling and dysfunction, eventually leading to heart failure. The limitations of conventional therapeutic and surgical interventions and lack of heart donors have necessitated the evolution of alternate treatment approaches for MI. Polysaccharide hydrogel based repair of infarcted myocardium have surfaced as viable option for MI treatment. Polysaccharide hydrogels may be injectable hydrogels or cardiac patches. Injectable hydrogels can in situ deliver cells and bio-actives, facilitating in situ cardiac regeneration and repair. Polysaccharide hydrogel cardiac patches reduce cardiac wall stress, and inhibit ventricular expansion and promote angiogenesis. Herein, we discuss about MI pathophysiology and myocardial microenvironment and how polysaccharide hydrogels are designed to mimic and support the microenvironment for cardiac repair. We also put forward the versatility of the different polysaccharide hydrogels in mimicking diverse cardiac properties, and acting as a medium for delivery of cells, and therapeutics for promoting angiogenesis and cardiac repair. The objectives of this review is to summarize the factors leading to MI and to put forward how polysaccharide based hydrogels promote cardiac repair. This review is written to enable researchers understand the factors promoting MI so that they can undertake and design novel hydrogels for cardiac regeneration.

H-ras-targeted genetic therapy remarkably surpassed docetaxel treatment in inhibiting chemically induced hepatic tumors in rats.

AIMS: Hepatocellular carcinoma (HCC) is still a leading cause of cancer-related death worldwide. But its chemotherapeutic options are far from expectation. We here compared H-ras targeted genetic therapy to a commercial docetaxel formulation (DXT) in inhibiting HCC in rats. MAIN METHODS: After the physicochemical characterization of phosphorothioate-antisense oligomer (PS-ASO) against H-ras mutated gene, the PS-ASO-mediated in vitro hemolysis, in vivo hepatic uptake, its pharmacokinetic profile, tissue distribution in some highly perfused organs, its effect in normal rats, antineoplastic efficacy in carcinogen-induced HCC in rats were evaluated and compared against DXT treatment. Mutated H-ras expression by in situ hybridization, hep-par-I, CK-7, CD-15, p53 expression patterns by immunohistochemical methods, scanning electron microscopic evaluation of hepatic architecture, various hepatic marker enzyme levels and caspase-3/9 apoptotic enzyme activities were also carried out in the experimental rats. KEY FINDINGS: PS-ASO showed low in vitro hemolysis (<3 %), and had a sustained PS-ASO blood residence time in vivo compared to DTX, with a time-dependent hepatic uptake. It showed no toxic manifestations in normal rats. PS-ASO distribution was although initially less in the lung than liver and kidney, but at 8 h it accumulated more in lung than kidney. Antineoplastic potential of PS-ASO (treated for 6 weeks) excelled in inhibiting chemically induced tumorigenesis compared to DTX in rats, by inhibiting H-ras gene expression, some immonohistochemical modulations, and inducing caspase-3/9-mediated apoptosis. It prevented HCC-mediated lung metastatic tumor in the experimental rats. SIGNIFICANCE: PS-ASO genetic therapy showed potential to inhibit HCC far more effectively than DXT in rats.

Research progresses on carboxymethyl xanthan gum: Review of synthesis, physicochemical properties, rheological characterization and applications in drug delivery.

Xanthan gum is a nonionic polysaccharide widely explored in biomedical, nutraceutical, and pharmaceutical fields. XG suffers from several drawbacks like poor dissolution, lower bioavailability and an inability to form hydrogels. The carboxymethyl derivative of XG, CMX, has better solubility, dissolution, and bioavailability characteristics. Moreover, due to its anionic character, it forms water insoluble hydrogels upon crosslinking with metal cations. CMX hydrogels are used to prepare matrix tablets, microparticles, beads, and films. CMX hydrogels has been used in drug delivery and tissue engineering fields. CMX hydrogels are used for sustained gastrointestinal, colon targeted, and transdermal delivery of drugs. CMX nanoparticles have been used for targeted delivery of anticancer drugs to tumor cells. CMX hydrogels have already made significant strides in drug delivery and tissue engineering fields. Further understanding of the physicochemical properties and rheological characteristics of CMX would enable researchers to explore newer applications of CMX. This review article thus aims to discuss the synthesis, physicochemical properties, and rheological characteristics of CMX. The article also gives critical insights on the versatility of CMX as a drug delivery carrier and presents prospective trends on applications of CMX.

Effect of intragranular/extragranular tara gum on sustained gastrointestinal drug delivery from semi-IPN hydrogel matrices.

The present research was undertaken to develop semi-IPN hydrogel matrix tablets of tara gum (TG) and carboxymethyl TG (CMTG) for sustained gastrointestinal delivery of highly water soluble tramadol hydrochloride (TH). The matrix tablets were developed by a hybrid process of wet granulation and direct compression technique. Carboxymethyl TG was crosslinked with dual cross-linking ions (Al3+/Ca2+). The uncross-linked component of the semi-IPN matrix was either incorporated within the granules (intragranular TG) or incorporated outside the granules (extragranular TG), prior to compression. The effect of intragranular/extragranular TG on the swelling, erosion and TH release characteristics from the semi-IPN hydrogel matrix tablets was investigated. The key finding of the investigation indicated that intragranular TG expedited TH release, while extragranular TG sustained TH release. Moreover, the effect of cross-linking ions on viscosity, rigidity, cross-link density and TH release behavior from hydrogel matrices was investigated. In-vivo pharmacokinetic performance of the optimized extragranular TG semi-IPN hydrogel matrix (F15) indicated sustained TH release in gastrointestinal milieu.

Carboxymethylated Gums and Derivatization: Strategies and Significance in Drug Delivery and Tissue Engineering.

Natural polysaccharides have been widely exploited in drug delivery and tissue engineering research. They exhibit excellent biocompatibility and fewer adverse effects; however, it is challenging to assess their bioactivities to that of manufactured synthetics because of their intrinsic physicochemical characteristics. Studies showed that the carboxymethylation of polysaccharides considerably increases the aqueous solubility and bioactivities of inherent polysaccharides and offers structural diversity, but it also has some limitations that can be resolved by derivatization or the grafting of carboxymethylated gums. The swelling ratio, flocculation capacity, viscosity, partition coefficient, metal absorption properties, and thermosensitivity of natural polysaccharides have been improved as a result of these changes. In order to create better and functionally enhanced polysaccharides, researchers have modified the structures and properties of carboxymethylated gums. This review summarizes the various ways of modifying carboxymethylated gums, explores the impact that molecular modifications have on their physicochemical characteristics and bioactivities, and sheds light on various applications for the derivatives of carboxymethylated polysaccharides.

Al3+/Ca2+ cross-linked hydrogel matrix tablet of etherified tara gum for sustained delivery of tramadol hydrochloride in gastrointestinal milieu.

Tara gum (TG) was derivatized to carboxymethyl TG (CMTG) and then cross-linked with Al3+/Ca2+ ions to prepare Al/Ca cross-linked CMTG matrices for sustained delivery of Tramadol Hydrochloride (TH), a highly water-soluble drug. The effect of Al3+/Ca2+ ions concentration on swelling, erosion, and drug release behavior from Al/Ca-CMTG matrices was investigated. Al-CMTG matrices had greater cross-linking density, produced a more rigid and denser hydrogel layer than Ca-CMTG matrices. The rate of swelling, erosion, and in vitro drug release from Al-CMTG matrices was slower than from Ca-CMTG matrices. The most important finding of our study indicated that at the same concentration of cross-linking ions, the release of TH from Al-CMTG matrices was slower compared to Ca-CMTG matrices. The optimized formulation containing 9 % w/w AlCl3 in CMTG matrices released TH in a sustained manner up to 12 h in the gastrointestinal milieu. Moreover, it was observed that the prepared optimized formulation exhibited a more sustained release of TH compared to the marketed product.

A review on challenges and issues with carboxymethylation of natural gums: The widely used excipients for conventional and novel dosage forms.

Diverse properties of natural gums have made them quite useful for various pharmaceutical applications. However, they suffer from various problems, including unregulated hydration rates, microbial degradation, and decline in viscosity during warehousing. Among various chemical procedures for modification of gums, carboxymethylation has been widely studied due to its simplicity and efficiency. Despite the availability of numerous research articles on natural gums and their uses, a comprehensive review on carboxymethylation of natural gums and their applications in the pharmaceutical and other biomedical fields is not published until now. This review outlines the classification of gums and their derivatization methods. Further, we have discussed various techniques of carboxymethylation, process of determination of degree of substitution, and functionalization pattern of substituted gums. Detailed information about the application of carboxymethyl gums as drug delivery carriers has been described. The article also gives a brief account on tissue engineering and cell delivery potential of carboxymethylated gums.

Moringa gum and its modified form as a potential green polymer used in biomedical field.

Over the past few decades, natural gums are extensively investigated by the researchers due to their beneficial physicochemical properties. Among them, the polysaccharide exudates obtained from the stem of the plant Moringa oleifera, known as moringa gum, is investigated widely in the food, pharmaceutical, and other areas. The moringa gum is used in the form of dried powder as a pharmaceutical excipient in various formulations. It is also derivatized either by grafting or by other chemical modifications for enhancing its properties. The research on moringa gum and modified moringa gum has diversified in numerous biomedical fields. However, summarization of these progress are not available in the literature. This article gives an overview of the collection, purification, structural elucidation, and modification of moringa gum. Moreover, the present review furnishes complete information on the various aspects of moringa gum and its applications in various industrial and biomedical fields.

Enhanced intestinal stability and pH sensitive release of quercetin in GIT through gellan gum hydrogels.

The objective of the work was to improve the intestinal stability and pH sensitive release of quercetin in the gastrointestinal tract. To achieve this aim, novel quercetin loaded pH sensitive hydrogel beads of gellan gum were developed through an ionic cross-linking technique using calcium chloride (CaCl2) as cross-linking agents. Field emission scanning electron microscopy (FESEM) was used to characterize the morphological appearance of the prepared hydrogel beads. Drug-polymer and drug-CaCl2 interaction were studied by using infrared spectroscopy. The important finding of the study was the formation of stable hydrogel beads at a very low concentration of CaCl2 (0.3 % w/v). There was a drug polymer interaction in addition to polymer and CaCl2 interaction that is confirmed by infrared spectroscopy. All the formulation shows good entrapment efficiencies within the range of 58.56-93.71 %. The prepared beads exhibited a pH responsive swelling behavior with maximum swelling at the simulated intestinal fluid (pH 7.4) (SIF). Hydrogel beads also showed a pH responsive release behavior and sustained release of drug at SIF. Moreover, the intestinal stability of quercetin was improved when encapsulated in gellan gum hydrogel beads in comparison to the solution containing quercetin.

Xyloglucan as green renewable biopolymer used in drug delivery and tissue engineering.

Xyloglucan is a mucoadhesive polysaccharide which is extracted from the cell wall of vascular plants. Tamarind seeds are the abundant source of xyloglucan and commercially more popular. It is biocompatible, biodegradable, and nontoxic in nature. It is approved by the FDA for use as a food additive, stabilizing and thickening agent or gelling agent. Recently, many researchers are giving attention to xyloglucan for drug delivery through various routes and regeneration of the number of tissues. However, the findings of tissue regeneration and drug delivery in combination are not collected and represented in a simple and comprehensive way. The aim of this review is to find and represent these missing links. This review presents current researches on xyloglucan in drug delivery and regeneration of tissue.

Polysaccharide as renewable responsive biopolymer for in situ gel in the delivery of drug through ocular route.

The major complications associated with the administration of ocular dosage forms are the precorneal loss due to the nasolacrimal drainage and high turnover of tear fluid. In situ forming gels are developed to overcome these complications. In situ gelling systems are polymeric solutions converted into a viscoelastic gel in the ocular surface due to a change in temperature, ionic strength, and pH. Recently, the use of responsive polysaccharides containing in situ gel formulation has increased due to its biocompatible nature, non-toxicity, and biodegradability. The research on in situ gel using polysaccharide in the delivery of drug molecules through the ocular route has diversified in various fields. However, there is no report are available that summaries this progress. The aim of this article is to bridge that lacuna. We discuss different polysaccharides based in situ gel including pH, temperature, ion and multiple sensitive used in ocular drug delivery. The nanoformulation incorporated polysaccharide in situ gels for ocular drug delivery has also been highlighted.

Breaking the Barrier of Cancer through Papaya Extract and their Formulation.

BACKGROUND: In the last decade, many new avenues of cancer treatment have opened up but the costs of treatment have sky-rocketed too. Hence, screening of indigenously available plant and animal resources for anti-carcinogenic potential is an important branch of anticancer research. The effort has been made through this comprehensive review to highlight the recent developments of anticancer therapies using different parts of papaya plant extract. METHODS: In search of the naturally existing animals and plants for anticarcinogenic potential, papaya plant has been exploited by the scientist working in this research field. A widespread literature search was performed for writing this review. RESULTS: Different constituents of Carica papaya responsible for anticancer activities have been discussed. Papaya extract for the treatment of breast, liver, blood, pancreas, skin, prostate, and colon cancer have also been reported. Finally, the various formulation approach using Carica papaya extract have been highlighted. CONCLUSION: The information provided in this review might be useful for researchers in designing of novel formulation of Carica papaya extract for the treatment of cancer.

Breaking the barricade of oral chemotherapy through polysaccharide nanocarrier.

Oral chemotherapy is the most preferred drug administration method due to non-invasive administration, more convenient, low healthcare cost, and patient compliance in comparison to intravenous chemotherapy. However, oral chemotherapy poses numerous hurdles to drug absorption through the gastrointestinal tract. Recently, nanocarriers have been extensively used for delivering anticancer drugs orally. Nanocarriers present distinctive advantages that comprise aiding drug dissolution owing to high surface to volume ratio, surface modifiability, protecting drugs from the harsh gastrointestinal environments and other features, all of which contribute to enhanced drugs bioavailability. Nanocarriers based on polysaccharides have emerged as the favored choice owing to their low/non-toxicity, biodegradability, and biocompatibility. In the last decade, the research on oral delivery of anticancer drug using polysaccharide nanocarrier has diversified in many fields. Yet there is no report that summaries these advances. This article aims to bridge that lacuna. In this review article, we have discussed the problems associated with oral chemotherapy and conquer these through polysaccharide nanocarriers. This review also provides a general idea on the current developments in polysaccharide nanocarrier for oral bioavailability enhancement of anticancer drugs.

Extraction of levetiracetam for therapeutic drug monitoring by transdermal reverse iontophoresis.

Recently, transdermal reverse iontophoresis across the skin has been investigated as a novel technology for the purpose of diagnosis as well as therapeutic drug monitoring. Accordingly, the objective of this study was to investigate ex vivo and in vivo transdermal extraction of levetiracetam, an antiepileptic drug, across the pig ear skin by reverse iontophoresis. Reverse iontophoresis experiments were performed using three chambered diffusion cells. Extractions profiles were generated in phosphate buffers at different current intensities, pH and ionic strength as well donor drug concentrations. This was followed by ex vivo extraction in gels and in vivo extractions using New Zealand rabbits. Results indicate that levetiracetam was extracted at both anode and cathode. Flux values were unaffected by increase in current intensities (0.5 mA and 0.6 mA) but affected by pH and ionic strength. Neither in cathodal nor in anodal extraction, flux values did show a proportional relationship with the donor drug concentration. At low and medium concentration levels, flux values did not show any major change but the extraction flux at high donor concentration was much higher. In contrast, in vivo experiment with rabbits resulted in wide variation of fluxes with very high fluxes recorded at the cathodal end. Reasons attributed to this difference may include lower current intensity, and species variation. The most significant finding of this study is that measurable amounts of the levetiracetam were extracted at both the ends indicating its feasibility for non-invasive drug monitoring.

Current Status of Stem Cell Therapies in Tissue Repair and Regeneration.

Tissue engineering is a multi-disciplinary field such as material science, life science, and bioengineering that are necessary to make artificial tissue or rejuvenate damaged tissue. Numerous tissue repair techniques and substitute now exist even though it has several shortcomings; these shortcomings give a good reason for the continuous research for more acceptable tissue-engineered substitutes. The search for and use of a suitable stem cell in tissue engineering is a promising concept. Stem cells have a distinctive capability to differentiate and self-renew that make more suitable for cell-based therapies in tissue repair and regeneration. This review article focuses on stem cell for tissue engineering and their methods of manufacture with their application in nerve, bone, skin, cartilage, bladder, cardiac, liver tissue repair and regeneration.

Breaking the Barrier of Cancer Through Liposome Loaded with Phytochemicals.

Currently, the most important cause of death is cancer. To treat the cancer there are a number of drugs existing in the market but no drug is found to be completely safe and effective. The toxicity of the drugs is the key problem in the cancer chemotherapy. However, plants and plant derived bioactive molecule have proved safe and effective in the treatment of cancers. Phytochemicals that are found in fruits, vegetables, herbs, and plant extract have been usually used for treating cancer. It has been established that several herbal drug have a strong anticancer activity. However, their poor bioavailability, solubility, and stability have severely restricted their use. These problems can be overcome by incorporating the herbal drug in nanolipolomal vesicles. In last few decades, researcher have used herbal drug loaded nanoliposome for the treatment and management of a variety of cancers. Presently, a number of liposomal formulations are on the market for the treatment of cancer and many more are in pipe line. This review discusses about the tumor microenvironment, targeting mechanism of bioactive phytochemicals to the tumor tissue, background of nanoliposome, and the potential therapeutic applications of different bioactive phytochemicals loaded nanoliposome in cancer therapy.

Transdermal reverse iontophoresis: A novel technique for therapeutic drug monitoring.

Application of transdermal reverse iontophoresis for diagnostic purpose is a relatively new concept but its short span of research is full of ups and downs. In early nineties, when the idea was floated, it received a dubious welcome by the scientific community. Yet to the disbelief of many, 2001 saw the launching of GlucoWatch® G2 Biographer, the first device that could measure the blood sugar level noninvasively. Unfortunately, the device failed to match the expectation and was withdrawn in 2007. However, the concept stayed on. Research on reverse iontophoresis has diversified in many fields. Numerous in vitro and in vivo experiments confirmed the prospect of reverse iontophoresis as a noninvasive tool in therapeutic drug monitoring and clinical chemistry. This review provides an overview about the recent developments in reverse iontophoresis in the field of therapeutic drug monitoring.

Nano-encapsulation of capsaicin on lipid vesicle and evaluation of their hepatocellular protective effect.

The intention of the study was to evaluate the effectiveness of nanocapsulated food constituent capsaicin in protection of liver oxidative stress. We had prepared phospholipid vesicle (nanoliposome) by formation of thin lipid film followed by hydration when the mean vesicle diameter was found to be 277.7nm. Protection from sodium fluoride (NaF) induced oxidative stress by capsaicin loaded nanoliposomal formulation were tested in rats where a single dose of capsaicin in free and nanoliposome forms were administered after two hour of exposure to NaF. Membrane in hepatic cells were damaged by NaF and it was evaluated by estimating reactive oxygen species (ROS), lipid peroxidation, and catalase activity when it was observed that free capsaicin produced mild protection whereas liposomal capsaicin exerted a significant result. This can be suggested that liposome encapsulating capsaicin acts as a promising therapeutic agent in reducing liver oxidative stress produced by different stress factors.

Infringement of the barriers of cancer via dietary phytoconstituents capsaicin through novel drug delivery system.

Cancer is the major cause of fatality and the number of new cases is increasing incessantly. Conventional therapies and existing anticancer agents cause serious side effects and expand the patient's lifespan by a few years. There is the need to exploit alternative anticancer agents and novel drug delivery system to deliver these agents to the tumor site for the prevention of cancer. Recently, biologically active compounds isolated from plants used for the management of cancer have been the heart of interest. Capsaicin is a major pungent agent present in the chili peppers that is heavily consumed in the world. Capsaicin has demonstrated effectiveness as an anticancer agent, but a restraining factor is its pungency, extremely low aqueous solubility, and poor oral bioavailability which impede its use as an anticancer agent. Many technologies have been developed and applied to conquer this drawback. We bring to light the benefits of this phytoconstituent for treating different types of cancer. We also discussed some of the delivery approaches that have already made an impact by either delivering a drug to target tissue or increasing its bioavailability by many folds.

Prospects of pharmaceuticals and biopharmaceuticals loaded microparticles prepared by double emulsion technique for controlled delivery.

Several methods and techniques are potentially useful for the preparation of microparticles in the field of controlled drug delivery. The type and the size of the microparticles, the entrapment, release characteristics and stability of drug in microparticles in the formulations are dependent on the method used. One of the most common methods of preparing microparticles is the single emulsion technique. Poorly soluble, lipophilic drugs are successfully retained within the microparticles prepared by this method. However, the encapsulation of highly water soluble compounds including protein and peptides presents formidable challenges to the researchers. The successful encapsulation of such compounds requires high drug loading in the microparticles, prevention of protein and peptide degradation by the encapsulation method involved and predictable release, both rate and extent, of the drug compound from the microparticles. The above mentioned problems can be overcome by using the double emulsion technique, alternatively called as multiple emulsion technique. Aiming to achieve this various techniques have been examined to prepare stable formulations utilizing w/o/w, s/o/w, w/o/o, and s/o/o type double emulsion methods. This article reviews the current state of the art in double emulsion based technologies for the preparation of microparticles including the investigation of various classes of substances that are pharmaceutically and biopharmaceutically active.