Prasenjit Mukherjee

Development of New Localized Drug Delivery System Based on Ceftriaxone-Sulbactam Composite Drug Impregnated Porous Hydroxyapatite: A Systematic Approach for In Vitro and In Vivo Animal Trial

ABSTRACTPurposePresent investigation deals with an extensive approach incorporating in vitro and in vivo experimentation to treat chronic osteomyelitis, using hydroxyapatite porous scaffolds.Materials and MethodsHydroxyapatite was synthesized in the laboratory by wet chemical method, different porous scaffolds have been fabricated. In vitro studies include variation of porosity with interconnectivity, pore-drug interfacial studies by SEM-EDAX and drug elution studies (by HPLC) both in contact with PBS and SBF at ~37°C. In vivo trials were based on experimental osteomyelitis in rabbit model induced in tibia by Staphylococcus aureus. Characterizations included observation of histopathology, radiology and estimation of drug in both bone and serum for 42 days by HPLC method and subsequent bone-biomaterial interface by SEM.ResultsIt was established that lower pore percentage with a distribution of mainly micro-pores were found to be superior over the higher pore percentage both in vitro and in vivo. The criteria was matched with the 50N50H samples which had 50–55% porosity with an average pore size ~110 μm, having higher interconnectivity (10–100 μm), moderately high adsorption efficiency (~50%) when loaded with CFS (drug combinations consisting of irreversible b-lactamase inhibitor and b-lactam antibiotic). CFS release from HAp implants were faster in PBS than SBF. Further, both the results of in vitro and in vivo drug elution after 42 days showed release higher than minimum inhibitory concentration of CFS against Staphylococcus aureus. In vivo studies also proved the superiority of CFS loaded HAp implants than parenteral group based on eradication of infection and new bone formation.ConclusionsHAp based porous scaffold loaded with CFS and designed porosity (in terms of micro- and macro-porosity, interconnectivity) was found to be an ideal delivery system which could locally, sustainably release the composite antibiotic in reliable manner both in terms of in vitro drug elution behaviour in contact with SBF and in vivo animal trial.

Understanding osteomyelitis and its treatment through local drug delivery system

Chronic osteomyelitis is a major challenge in bone surgery. Conventional use of antibiotics is not an effective way to control the malaise due to so many reasons. Determination of optimal treatment strategy becomes difficult for the orthopaedic surgeons and as a consequence, the patients suffer not only from therapeutic failure but also due to adverse side effects of antibiotics and financial loss due to additional stay at hospitals. A wide application of carrier systems, as a medium for local delivery of antibiotics, is being used experimentally and clinically for the treatment of osteomyelitis. This kind of delivery system provides sustained higher concentration of antibiotics at the infection site with reduced possibility of toxicity. This review highlight etiology and pathophysiology of osteomyelitis, current therapeutic options with their limitations, and potentiality of biomaterial based carrier materials impregnated with antibiotics as local delivery approach.

Influence of single and binary doping of strontium and lithium on in vivo biological properties of bioactive glass scaffolds

Effects of strontium and lithium ion doping on the biological properties of bioactive glass (BAG) porous scaffolds have been checked in vitro and in vivo. BAG scaffolds were prepared by conventional glass melting route and subsequently, scaffolds were produced by evaporation of fugitive pore formers. After thorough physico-chemical and in vitro cell characterization, scaffolds were used for pre-clinical study. Soft and hard tissue formation in a rabbit femoral defect model after 2 and 4 months, were assessed using different tools. Histological observations showed excellent osseous tissue formation in Sr and Li + Sr scaffolds and moderate bone regeneration in Li scaffolds. Fluorochrome labeling studies showed wide regions of new bone formation in Sr and Li + Sr doped samples as compared to Li doped samples. SEM revealed abundant collagenous network and minimal or no interfacial gap between bone and implant in Sr and Li + Sr doped samples compared to Li doped samples. Micro CT of Li + Sr samples showed highest degree of peripheral cancellous tissue formation on periphery and cortical tissues inside implanted samples and vascularity among four compositions. Our findings suggest that addition of Sr and/or Li alters physico-chemical properties of BAG and promotes early stage in vivo osseointegration and bone remodeling that may offer new insight in bone tissue engineering.

Influence of topical anesthetics on oculocardiac reflex and corneal healing in rabbits.

AIM To investigate the incidence of oculocardiac reflex (OCR) with two anesthetic regimens and its prevention using topical anesthetics in a rabbit model, and to explore the effect of topical anesthetics on corneal healing. METHODS Forty-eight clinically healthy adult New Zealand white rabbits of either sex were divided into two groups (Group A and B) and anesthetized with either ketamine (Group A, n =24) or propofol (Group B, n =24). he incidence of OCR was recorded in each group with a variety of ocular manipulation with or without the use of topical anesthetics (40g/L lignocaine, 5g/L proparacain, 5g/L bupivacaine). Corneal toxicity and healing following the use of each topical anesthetic was assessed one day after surgery and up to 7 days postoperatively by clinical examination of the eye, histopathology and collagen staining and transmission electron microscopy. RESULTS No incidence of OCR was recorded with ocular manipulation under ketamine anesthesia, whereas significant reduction in heart rate (P<0.01) was recorded under propofol anesthesia. Topical anesthetics could successfully prevent the OCR without affecting the corneal healing. CONCLUSION Topical anesthetics may be recommended for prevention of OCR without any local adverse effect.

Sperm Morphology and Natural Biomolecules from Marine Snail Telescopium telescopium: a Phylogenetic Perspective

El analisis bioquimico de la fraccion aislada del citosol desde las glandulas ovotestes/espermateca del molusco marino Telescopium telescopium y su estructura tubular espermatica revelaron biomoleculas relativamente similares como tales como diferentes enzimas, hormonas, minerales y estructuras de los espermatozoides que tambien existen en los seres humanos. Por otra parte, en el antisuero de la fraccion citosolica se encontro una reaccion cruzada con los antigenos del esperma humano indicando la presencia de una superficie espermatica de antigenicidad comun entre estas dos diversificadas especies. Estos hallazgos pueden apoyar y/o hipotetizar sobre el origen y la diversificacion de las moleculas de los vertebrados desde su forma (s) ancestral desde los invertebrados, y funciones basicas fisiologicas de estas biomoleculas ancestrales incluyendo algunas de las estructuras celulares siendo plausiblemente las mismas, independientemente de sus cambios estructurales incluso despues de la evolucion.

Applications of Different Bioactive Glass and Glass-Ceramic Materials for Osteoconductivity and Osteoinductivity

ABSTRACT Throughout the world, research has been carried out in development of new methods and materials involving multidisciplinary approach for effective bone tissue repair and regeneration. Amid various biomaterials, bioactive glass material has drawn considerable attention due to their superior biocompatibility, degradability, ion leaching phenomena and propagation of osteogenic cells. In this concise review, effort has been made to summarize different material combinations available as composition to elaborate their biological properties both in vitro and in vivo, reaction kinetics in simulated body fluid, effect of different constituents of bioactive glass and glassceramic compositions, porosity, etc and finally these materials’ applications as bone graft substitutes and various clinical applications have been detailed. In this review an attempt has been made to sum up the recent advancement of different bioactive glass and composite materials for osteoconductivity and osteoinductivity in orthopaedic surgical challenges. GRAPHICAL ABSTRACT

Is lithium essential for epididymal sperm maturation

A wider biological role of ultratrace element lithium in the mammalian reproduction has been reported, however, presence of lithium in the epididymal luminal fluid (ELF) and its influence on sperm during maturation events in the epididymal regions are still unknown. A pilot study was carried out in Jamunapari buck which revealed that levels of lithium in the ELF diminished gradually and significantly (P<0.01) from caput to cauda epididymis, concomitantly, a distinct increase (P<0.01) in the spermatozoan motility, viability and hypo-osmotic reactive sperm were observed, except spermatozoan motility that was found absent in the caput epididymis. Therefore, we hypothesize that levels of lithium in the epididymal regions is one of the motility initiation and/or regulatory factor for epididymal sperm maturation essential for acquiring fertilizing competence of sperm cells, hence, lithium could also be considered as one of the biomarker of sperm maturation in any species.