Ramakrishna Vasireddi

Prophylactic Effects of Propranolol versus the Standard Therapy on a New Model of Disuse Osteoporosis in Rats

Disuse by bed rest, limb immobilization, or space flight causes rapid bone loss by arresting bone formation and accelerating bone resorption. Propranolol (a non-selective β-adrenergic antagonist) has been shown to improve bone properties by increasing bone formation and decreasing bone resorption in an ovariectomy-induced rat model. However, no studies have yet compared the osteoprotective properties of propranolol with well-accepted therapeutic interventions for the treatment and prevention of immobilization/disuse osteoporosis. To clarify this, we investigated the effects of propranolol compared with zoledronic acid and alfacalcidol in a new animal model of immobilization/disuse osteoporosis. Three-month-old male Wistar rats were divided into five groups with six animals in each group: (1) immobilized (IMM) control; (2) normal control; (3) IMM + zoledronic acid (50 μg/kg, intravenous single dose); (4) IMM + alfacalcidol (0.5 μg/kg, per oral daily); (5) IMM + propranolol (0.1 mg/kg, subcutaneously 5 days/week) for 10 weeks. In groups 1 and 3–5, the right hindlimb was immobilized. At the end of treatment, the femurs were removed and tested for bone porosity, bone mechanical properties, and cortical microarchitecture. Treatment with propranolol induced greater reductions in the bone porosity of the right femur and improved the mechanical properties of the femoral mid-shaft femur in comparison to the IMM control. Moreover, treatment with propranolol also improved the microarchitecture of cortical bones when compared with the IMM control, as indicated by scanning electron microscopy. The anti-osteoporotic property of propranolol was comparable with zoledronic acid and alfacalcidol. This study shows that the bone resorption induced by immobilization/disuse in rats can be suppressed by treatment with propranolol.

Risedronate/zinc-hydroxyapatite based nanomedicine for osteoporosis

Targeting of superior osteogenic drugs to bone is an ideal approach for treatment of osteoporosis. Here, we investigated the potential of using risedronate/zinc-hydroxyapatite (ZnHA) nanoparticles based formulation in a rat model of experimental osteoporosis. Risedronate, a targeting moiety that has a strong affinity for bone, was loaded to ZnHA nanoparticles by adsorption method. Prepared risedronate/ZnHA drug formulation was characterized by field-emission scanning electron microscopy, X-ray diffraction analysis and fourier transform infrared spectroscopy. In vivo performance of the prepared risedronate/ZnHA nanoparticles was tested in an experimental model of postmenopausal osteoporosis. Therapy with risedronate/ZnHA drug formulation prevented increase in serum levels of bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase 5b better than risedronate/HA or risedronate. With respect to improvement in the mechanical strength of the femoral mid-shaft and correction of increase in urine calcium and creatinine levels, the therapy with risedronate/ZnHA drug formulation was more effective than risedronate/HA or risedronate therapy. Moreover, risedronate/ZnHA drug therapy preserved the cortical and trabecular bone microarchitecture better than risedronate/HA or risedronate therapy. Furthermore, risedronate/ZnHA drug formulation showed higher values of calcium/phosphorous ratio and zinc content. The results strongly implicate that risedronate/ZnHA drug formulation has a therapeutic advantage over risedronate or risedronate/HA therapy for the treatment of osteoporosis.

Conceptual design of three-dimensional scaffolds of powder-based materials for bone tissue engineering applications

Purpose – The purpose of this paper is to investigate the possibility to construct tissue-engineered bone repair scaffolds with pore size distributions using rapid prototyping techniques. Design/methodology/approach – The fabrication of porous scaffolds with complex porous architectures represents a major challenge in tissue engineering and the design aspects to mimic complex pore shape as well as spatial distribution of pore sizes of natural hard tissue remain unexplored. In this context, this work aims to evaluate the three-dimensional printing process to study its potential for scaffold fabrication as well as some innovative design of homogeneously porous or gradient porous scaffolds is described and such design has wider implication in the field of bone tissue engineering. Findings – The present work discusses biomedically relevant various design strategies with spatial/radial gradient in pore sizes as well as with different pore sizes and with different pore geometries. Originality/value – One of the...

Effects of interface treatment on the fatigue behaviour of shape memory alloy reinforced polymer composites

Interfacial properties of Shape Memory Alloy (SMA) reinforced polymer matrix composites can be enhanced by improving the interfacial bonding. This paper focuses on studying the interfacial stresses developed in the SMAepoxy interface due to various laser shot penning conditions. Fiber-pull test-setup is designed to understand the role of mechanical bias stress cycling and thermal actuation cycling. Phase transformation is tracked over mechanical and thermal fatigue cycles. A micromechanics based model developed earlier based on shear lag in SMA and energy based consistent homogenization is extended here to incorporate the stress-temperature phase diagram parameters for modeling fatigue.

Photonic monitoring of chitosan nanostructured alginate microcapsules for drug release

By using a novel microfluidic set-up for drug screening applications, this study examines delivery of a novel risedronate based drug formulation for treatment of osteoporosis that was developed to overcome the usual shortcomings of risedronate, such as its low bioavailability and adverse gastric effects. Risedronate nanoparticles were prepared using muco-adhesive polymers such as chitosan as matrix for improving the intestinal cellular absorption of risedronate and also using a gastric-resistant polymer such as sodium alginate for reducing the gastric inflammation of risedronate. The in-vitro characteristics of the alginate encapsulated chitosan nanoparticles are investigated, including their stability, muco-adhesiveness, and Caco-2 cell permeability. Fluorescent markers are tagged with the polymers and their morphology within the microcapsules is imaged at various stages of drug release.

Enhancement Mechanism of Fluorescence Intensity in Presence of Plasmonic Nanoparticles

The emission intensity of fluorophore molecule may change in presence of strong plasmon field induced by nanoparticles. The enhancement intensity is optimized through selective clustering or functionalization of nanoparticles in closed vicinity of fluorophore. Our study is aimed at understanding the enhancement mechanism of fluorescence intensity in presence of gold nanoparticles to utilize it in molecular sensing and in situ imaging in the microfluidic lab-on-chip device. Related phenomena are studied in situ in a microfluidic channel via fluorescence imaging. Detailed analysis is carried out to understand the possible mechanism of enhancement of fluorescence due to nanoparticles. In the present experimental study we show that SYTO9 fluorescence intensity increased in presence of Au nanoparticles of ~20 nm diameter. The fluorescence intensity is 20 time more compared to that in absence of Au nanoparticles. The enhancement of fluorescence intensity is attributed to the plasmonic resonance of Au nanoparticle at around the fluorescence emission wavelength. Underlying fundamental mechanism via dipole interaction model is explored for quantitative correlation of plasmonic enhancement properties.

Plasmonic nanoparticle interaction with cell membrane for diagnostic applications

Optofluidic schemes of inhibition, transport and activation by carrier molecules through cell membrane have interesting applications. Through plasmonic excitation of nanoparticles integrated in microfluidic channel, we observe cell membrane structural changes. Related phenomena are studied in situ in a microfluidic channel via fluorescence imaging. Detailed analysis is carried out to understand the possible application of this scheme in optically induced transport and expression of cell membrane protein. Optical properties of the cells undergoing plasmonic transport are monitored and correlated to cell expression assay. Plasmonic charge transport and optical transmission are measured in the microfluidic lab-on-chip along with in-situ imaging.

Detection of target DNA using photo-reactive protoporphyrin moeity on a nanocomposite substrate

Detection of pathogens from infected biological samples through conventional process involves cell lysis and purification. The main objective of this work is to minimize the time and sample loss, as well as to increase the efficiency of detection of biomolecules. Electrical lysis of medical sample is performed in a closed microfluidic channel in a single integrated platform where the downstream analysis of the sample is possible. The device functions involve, in a sequence, flow of lysate from lysis chamber passed through a thermal denaturation counter where dsDNA is denatured to ssDNA, which is controlled by heater unit. A functionalized binding chamber of ssDNA is prepared by using ZnO nanorods as the matrix and functionalized with bifunctional carboxylic acid, 16-(2-pyridyldithiol) hexadecanoic acid (PDHA) which is further attached to a linker molecule 1-ethyl-3-(3-dimethylaminopropyl) (EDC). Linker moeity is then covalently bound to photoreactive protoporphyrin (PPP) molecule. The photolabile molecule protoporphyrin interacts with -NH2 labeled single stranded DNA (ssDNA) which thus acts as a probe to detect complimentary ssDNA from target organisms. Thereafter the bound DNA with protoporphyrin is exposed to an LED of particular wavelength for a definite period of time and DNA was eluted and analyzed. UV/Vis spectroscopic analysis at 260/280 nm wavelength confirms the purity and peak at 260 nm is reconfirmed for the elution of target DNA. Quantitative and qualitative data obtained from the current experiments show highly selective detection of biomolecule such as DNA which have large number of future applications in Point-of-Care devices.