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design and in vitro evaluation of controlled release alginate beads of diltiazem hydrochloride

Asian Pacific Journal of Tropical Medicine 2009年第4期2卷 46-49页

作者： d.Nagasamy Venkatesh A.Kalaivani kritika d.kalro Lalitha Chintha James Tharani M.K.Samanta B.Suresh department of Pharmaceutics JSS College of PharmacyOOTY-643001Tamil NaduIndia

Objective:Oral slow and sustained release drug delivery system can release their drug content with a controlled manner,producing a desirable blood serum level,reduction in drug toxicity and improving the patient compliance by prolonging dosing *** major drawback of orally administered drug like diltiazem as a calcium channel blocker for the treatment of angina pectoris,arrhythmia and *** has higher aqueous solubility and shorter elimination ***:To overcome these drawbacks associated with diltiazem,an attempt has been made to develop a sustained release dosage form of diltiazem embedded alginate microbeads by ionotropic gelation technique employing various concentrations of polymer and keeping the drug concentration ***:The beads were characterized for its particle size,drug content and in vitro release studies. The results revealed that the surface adhering drug was found to release immediately and a steady state of release was obtained up to 12 h from all the *** results indicated there was an inverse relationship between the concentration of alginate and drug *** drug release was found to follow non-fickian diffusion obeying first order ***:The developed alginate microbeads offered a sustained release of diltiazem. Hence,the formulated microbeads were found to be potential,cost effective,possess satisfactory in vitro release studies.

关键词： Sodium alginate diltiazem Microbeads Ionotropic gelation technique Peppa’s model

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A tissue-engineered rostral migratory stream for directed neuronal replacement

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Neural Regeneration Research 2018年第8期13卷 1327-1331页

作者： John C.O'donnell kritika S.Katiyar Kate V.Panzer d.Kacy Cullen Center for Brain Injury & Repair Department of Neurosurgery Perelman School of Medicine University of Pennsylvania Center for Neurotrauma Neurodegeneration & Restoration Corporal Michael Crescenz Veterans Affairs Medical Center School of Biomedical Engineering Drexel University department of Bioengineering School of Engineering and Applied Science University of Pennsylvania

New neurons are integrated into the circuitry of the olfactory bulb throughout the lifespan in the mamma- lian brain--including in humans. These new neurons are born in the subventricular zone and subsequently mature as they are guided over long distances via the rostral migratory stream through mechanisms we are only just beginning to understand. Regeneration after brain injury is very limited, and although some neuroblasts from the rostral migratory stream will leave the path and migrate toward cortical lesion sites, this neuronal replacement is generally not sustained and therefore does not provide enough new neurons to alleviate functional deficits. Using newly discovered microtissue engineering techniques, we have built the first self-contained, implantable constructs that mimic the architecture and function of the rostral migratory stream. This engineered microtissue emulates the dense cord-like bundles of astrocytic somata and processes that are the hallmark anatomical feature of the glial tube. As such, our living microtissue-en- gineered rostral migratory stream can serve as an in vitro test bed for unlocking the secrets of neuroblast migration and maturation, and may potentially serve as a living transplantable construct derived from a patient＇s own cells that can redirect their own neuroblasts into lesion sites for sustained neuronal replace- ment following brain injury or neurodegenerative disease. In this paper, we summarize the development of fabrication methods for this microtissue-engineered rostral migratory stream and provide proof-of-princi- ple evidence that it promotes and directs migration of immature neurons.

关键词： rostral migratory stream glial tube astrocyte neuroblast brain injury neural repair neural regeneration tissue engineering

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Restoring nervous system structure and function using tissue engineered living scaffolds

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Neural Regeneration Research 2015年第5期10卷 679-685页

作者： Laura A.Struzyna James P.Harris kritika S.Katiyar H.Isaac Chen d.Kacy Cullen Center for Brain Injury and Repair Department of NeurosurgeryPerelman School of MedicineUniversity of Pennsylvania Center for Neurotrauma Neurodegenerationand RestorationPhiladelphia Veterans Affairs Medical Center School of Biomedical Engineering Drexel University

Neural tissue engineering is premised on the integration of engineered living tissue with the host nervous system to directly restore lost function or to augment regenerative capacity following ner- vous system injury or neurodegenerative disease. disconnection of axon pathways - the long-distance fibers connecting specialized regions of the central nervous system or relaying peripheral signals - is a common feature of many neurological disorders and injury. However, functional axonal regenera- tion rarely occurs due to extreme distances to targets, absence of directed guidance, and the presence of inhibitory factors in the central nervous system, resulting in devastating effects on cognitive and sensorimotor function. To address this need, we are pursuing multiple strategies using tissue engi- neered ＂living scaffolds＂, which are preformed three-dimensional constructs consisting of living neural cells in a defined, often anisotropic architecture. Living scaffolds are designed to restore function by serving as a living labeled pathway for targeted axonal regeneration - mimicking key developmental mechanisms- or by restoring lost neural circuitry via direct replacement of neurons and axonal tracts. We are currently utilizing preformed living scaffolds consisting of neuronal dusters spanned by long axonal tracts as regenerative bridges to facilitate long-distance axonal regeneration and for targeted neurosurgical reconstruction of local circuits in the brain. Although there are formidable challenges in predinical and clinical advancement, these living tissue engineered constructs represent a promising strategy to facilitate nervous system repair and functional recovery.

关键词： living scaffolds neural tissue engineering cell transplant biomaterials regeneration neurotrauma neurodegeneration axon pathfinding cell migration

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Engineered neuronal microtissue provides exogenous axons for delayed nerve fusion and rapid neuromuscular recovery in rats

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Bioactive Materials 2022年第12期7卷 339-353页

作者： Justin C.Burrell Suradip das Franco A.Laimo kritika S.Katiyar Kevin d.Browne Robert B.Shultz Vishal J.Tien Phuong T.Vu dmitriy Petrov Zarina SAli Joseph M.Rosen d.Kacy Cullen Center for Brain Injury&Repair Department of NeurosurgeryPerelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPAUSA department of Bioengineering School of Engineering&Applied ScienceUniversity of PennsylvaniaPhiladelphiaPAUSA Center for Neurotrauma Neurodegeneration&RestorationCorporal Michael J.Crescenz Veterans Affairs Medical CenterPhiladelphiaPA19104USA Axonova Medical LLCPhiladelphiaPAUSA dartmouth-Hitchcock Medical Center Division of Plastic SurgeryDartmouth CollegeLebanonNHUSA

Nerve injury requiring surgical repair often results in poor functional recovery due to the inability of host axons to re-grow long distances and reform meaningful connections with the target muscle. While surgeons can re-route local axon fascicles to the target muscle, there are no technologies to provide an exogenous source of axons without sacrificing healthy nerves. Accordingly, we have developed tissue engineered neuromuscular interfaces (TE-NMIs) as the first injectable microtissue containing motor and sensory neurons in an anatomically-inspired architecture. TE-NMIs provide axon tracts that are intended to integrate with denervated distal structures and preserve regenerative capacity during prolonged periods without host innervation. Following implant, we found that TE-NMI axons promoted Schwann cell maintenance, integrated with distal muscle, and preserved an evoked muscle response out to 20-weeks post nerve transection in absence of innervation from host axons. By repopulating the distal sheath with exogenous axons, TE-NMIs also enabled putative delayed fusion with proximal host axons, a phenomenon previously not achievable in delayed repair scenarios due to distal axon degeneration. Here, we found immediate electrophysiological recovery after fusion with proximal host axons and improved axon maturation and muscle reinnervation at 24-weeks post-transection (4-weeks following delayed nerve fusion). These findings show that TE-NMIs provide the potential to improve functional recovery following delayed nerve repair.

关键词： Nerve regeneration Neuromuscular injury Muscle preservation Tissue engineering Microtissue Axon fusion

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