Pravin Shende

Novel cyclodextrin nanosponges for delivery of calcium in hyperphosphatemia.

Cyclodextrin nanosponges are solid, porous nanoparticulate three dimensional structures, have been used as delivery system of different drugs. In this work, new cyclodextrin-based nanosponges of calcium carbonate were prepared by polymer condensation method to release the calcium in controlled manner in the treatment of hyperphosphatemia as novel carriers. SEM measurements revealed their roughly spherical shape, porous nature and mean particle size of about 400 nm. Zeta potentials of the nanosponges were sufficiently high to obtain stable formulations. The encapsulation efficiencies of calcium in nanosponge formulations were found to be 81-95%. The moisture contents of the nanosponges were in the range of 0.1-0.7%. The optimized formulation produces enteric and controlled release kinetics of calcium in the management and treatment of hyperphosphatemia. It was also observed that calcium ions bound efficiently to free phosphate in a pH-dependent fashion especially at pH 7. In accelerated stability study no significant changes occurred in physical appearance, size and nature of drug in formulation for 3 months. The results of FTIR and DSC confirmed that calcium carbonate was encapsulated in nanosponges structure.

Acute and Repeated Dose Toxicity Studies of Different β-Cyclodextrin-Based Nanosponge Formulations

Nanosponges (NS) show promising results in different fields such as medicine, agriculture, water purification, fire engineering and so on. The present study was designed to evaluate toxicity of different NS formulations (namely, S1-S6) synthesized with different cross-linking agents such as carbonyl diimidazole, pyromellitic dianhydride and hexamethylene diisocynate; and preparation methods in experimental animals. Acute and repeated dose toxicity studies of formulations were carried out as per OECD guidelines 423 and 407, respectively. For acute toxicity study, formulations were administered to female rats at doses of 300 and 2000 mg/kg orally. The general behaviour of the rats was continuously monitored for 1 h after dosing, periodically during the first 24 h and daily thereafter for a total of 14 days. On day 14, animals were fasted overnight, weighed, and sacrificed. After sacrification, animals were subjected to necropsy. For repeated dose toxicity study, rats of either sex were orally administered with formulations at the dose of 300 mg/kg per day for a period of 28 days. The maximally tolerated dose of all formulations was found to be 2000 mg/kg. Repeated administration of formulations for 28 days did not show any significant changes in haematological and biochemical parameters in experimental animals. These results indicate that the formulations are safe, when tested in experimental animals.

Biomimetic estimation of glucose using non-molecular and molecular imprinted polymer nanosponges.

The aim of the present work was to develop biomimetics for glucose estimation using molecularly and non-molecularly imprinted polymers of pyromellitic dianhydride crosslinked β-cyclodextrin based nanosponges. The ionic association of glucose phosphate to nanosponges by polymerization reaction and removal of glucose created molecular imprinted polymer (MIP)-nanosponges with affinity for glucose binding. Particle size, zeta potential, glucose binding studies and FTIR were used to characterize molecular and non-molecular imprinted polymer (NIP) nanosponges. Particle size of the nanosponges was found in the range of 450.81±5.33 nm to 550.63±8.14 nm with low polydispersity index. MIP-nanosponges retained a relatively large population of pores in the nano-range, while NIP was related to the nonporous materials with weak interaction and had poor tendency to aggregate. Nanosponges showed the variation in binding capacities and specificities; and also exhibited a similar degree of swelling. Moreover electrostatic force of attraction and cavities specific fitting of glucose in MIP-nanosponges might be due to advance selectivity and affinity for glucose. FTIR study showed glucose molecules might be entered into the selective binding cavities, which were created by the extraction of template molecules It is concluded that nanosized MIP-nanosponges have advantages over conventional NIP due to diffusion of template in the formed cavity as of its high surface area.

Physicochemical Investigation of Engineered Nanosuspensions Containing Model Drug, Lansoprazole

Lansoprazole is a proton-pump inhibitor used in treatment of gastric ulcers, gastroesophageal reflux disease (GERD), and Zollinger–Ellison syndrome. The objective of the study was physicochemical investigation and comparative characterization of nanosuspensions of lansoprazole by complexing with β-cyclodextrin and β-cyclodextrin-based nanosponges to enhance its solubility and stability. Inclusion complexes of lansoprazole with β-cyclodextrin and nanosponges were prepared by physical method and polymer condensation method, respectively. Particle size, zeta potential, encapsulation efficiency, in vitro release, FTIR, and Differential Scanning Calorimeter (DSC) studies were used as characterization parameters. The average particle size of lansoprazole nanoparticles was found to be in the range of 178.7 ± 6.39 nm to 204.9 ± 2.91 nm. The high zeta potential values were attained to ensure a high-energy barrier and favor a good stability of nanosuspensions. In vitro release study showed the controlled release of lansoprazole, which was more satisfactory than individual drug. FTIR spectroscopy showed that there was interaction of cyclodextrin and its nanosponges with drug. DSC study revealed that drug was involved in complexion with cyclodextrin and nanosponges. Solubility and stability of lansoprazole were remarkably improved by inclusion complexation. Based on these findings, it can be concluded that engineered nanosuspension of lansoprazole is a promising carrier for nanoparticulate drug delivery in gastric ulcer. GRAPHICAL ABSTRACT

Pathophysiology, mechanisms and applications of mesenchymal stem cells for the treatment of spinal cord injury

Spinal Cord Injury (SCI) is a serious devastating condition associated to the high chances of morbidity and mortality. It involves a primary and a secondary injury, former cause damages to both lower and upper motor neurones and disrupts sensory, motor and autonomic functions while the latter involves various stages of molecular plus cellular incidents which elaborate the original injury. In the treatment of SCI, stem cells possess a good therapeutic potential. Bone marrow, adipose tissue, placenta, amniotic fluid and umbilical cord are the good sources for mesenchymal stem cells. This review article shows the uses of bone marrow derived mesenchymal cells in the treatment of acute and chronic case of SCI and its future scope.

Functionalized nanosponges for controlled antibacterial and antihypocalcemic actions

The aim of the present work was to develop lysozyme impregnated surface-active nanosponges to maintain its conformational stability and break bacterial cell walls by catalyzing the hydrolysis of 1,4-β-linkages between N-acetyl-d-glucosamine and N-acetylmuramic acid residues present in peptidoglycan layer surrounding the bacterial cell membrane, and for controlling the release of calcium in hypocalcemia condition. Different carbonyl diimidazole cross-linked β-cyclodextrin nanosponges with and without CaCO3 and CMC were prepared by polymer condensation method. The surface-active nanosponges were impregnated by lysozyme due to their ability to adsorb protein. Lysozyme impregnated nanosponges had a monomodal particle size distribution of 347.46±3.07 to 550.34±5.23nm, with a narrow distribution. The zeta potentials were sufficiently increased upon lysozyme impregnation, suggesting stable formulations by preventing aggregation. The in vitro release studies showed controlled release of lysozyme and calcium over a period of 24h. FTIR studies confirmed the impregnation of lysozyme on nanosponges and encapsulation of calcium in nanosponges. Lysozyme formulation showed promising conformational stability by DSC. It can be concluded that the stable nanosponges formulation is a promising carrier for antibacterial protein and preventing depletion of calcium in antibiotic associated hypocalcemic condition.

Cytotherapy using stromal cells: Current and advance multi-treatment approaches

The research in stem cells gives a proper information about basic mechanisms of human development and differentiation. The use of stem cells in new medicinal therapies includes treatment of different conditions such as spinal cord injury, diabetes mellitus, Parkinsonism, and cardiac disorders. These cells exhibit two unique properties: self-renewal and differentiation. The major stem cells been used for approximately about 10-14 years for cellular therapy are mesenchymal stem cells. Mesenchymal stem cells can individualize into many lineage, i.e. into both mesenchymal and non-mesenchymal lineage, such as into osteoblasts, chondrocytes, myocytes, adipocytes, neurons, etc. This review focuses on the history, types of stem cells and their targets and mechanisms of mesenchymal stem cells. Mesenchymal stem cells are the significant futuristic carrier for treating diseases associated not only with regeneration but also immunomodulation.

Current trends and emerging diagnostic techniques for lung cancer

Cancer is one of most fatal forms of disease with rapid, abnormal and uncontrolled division of cells which spreads into different organs in the body. The primary aim of this review is to showcase the current and emerging diagnostic techniques that are used in lung cancer detection. Lung cancer is a leading cause of death among smokers and it has been emerging in non-smokers due to passive smoke inhalation by non-smokers. The mortality rate of patients with lung cancer is very high due to the change in lifestyle and environmental factors. It is often misdiagnosed as tuberculosis in India as tuberculosis is prevalent in India. On the contrary tuberculosis is not prevalent in the western countries Like U.S.A., U.K., Canada, etc. The major setback in lung cancer is that the symptoms of lung cancer occur at very later stages when the tumor has spread profusely. Hence, highly advanced techniques are employed for detection, accurate staging and treatment of lung cancer. The review focuses on the various novel and emerging diagnostic tools like biomarkers and biosensors, radiogenomics and artificial intelligence. This review also gives an insight of the various conventional techniques like CT-imaging, sputum cytology, biopsy and bronchoscopy which have been modified over the years for better sensitivity and accuracy. It also encompasses the regulatory provisions like IDE, CLIA-certification, etc. for manufacturing and sale of diagnostics in India, U.S.A., Japan and Australia.

Pharmacotherapeutic approaches for transportation of anticancer agents via skin

Abstract Cancer is the largest family of diseases that involve abnormal uncontrolled cell growth which metastasizes to other parts of the body. The most common type of cancers includes lung, liver, colorectal, prostate, stomach, breast and cervical cancer with skin cancer excluding melanoma (contribute up to 40% of the cases). The conventional treatment approaches like surgery, chemotherapy, etc., have several side effects such as severe inflammation and pain. Hence, pharmacotherapeutic approaches of antineoplastic agents can be advantageous for treating various forms of cancer through the skin. Novel transdermal techniques and preparations have been emerged to overcome the limitations of skin and to penetrate inside the cancerous cells by transporting through the deeper tissues of the skin. The transdermal penetration of drugs using different formulations such as nanocarriers, physical penetration enhancement techniques, chemical penetration enhancers and newer technologies such as gels, dendrimers, needle-free injection jet etc., show improved patient compliance, abolition of scars and economic value. The topical delivery of antineoplastic agents is an attractive choice for increasing site-specific delivery, reducing side effects and improving therapeutic effects. The objective of this review is to present insights into pharmacotherapeutic techniques, which can be used for transdermal delivery of anticancer agents through skin due to its potential to create a new frontier in treatment of cancer.