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Pulmonary Delivery of antitubercular drugs using ligand anchored pH sensitive liposomes for the treatment of Pulmonary Tuberculosis. - Current drug delivery
Aim of the present study wasdevelopment and characterization of ligand anchored pH sensitive liposomes (PSL) as dry powder inhaler for thetargeted delivery of drugs in the target site i.e. lungs. Ligand anchored PSL (TPSL)was prepared by thin film hydrationfor the combined delivery of Isoniazid (INH) and Ciprofloxacin HCl (CIP HCl) using 4-aminophenyl-É‘-D mannopyranoside (Man) as surface functionalized ligand. It was observed that size of the ligand anchored liposomes (TPSL) were slightly more than the non-ligand anchored liposomes (PSL). Drug release was studied at different pH for 24 hrs and it was observed that liposomes exhibited slow release at alkaline pH (58-64%) as compared to macrophage pH(81-87%) where it increased dramatically due to the destabilization of pH sensitive liposome (PSL). In vitro cellular uptake study showed that much higher concentration was achieved in the alveolar macrophage using ligand anchored liposomes as compared to its counterpart. In vivo study showed that maximum drug accumulation was achieved in the lung by delivering drug using ligand anchored PSL (approximately 12-13 %) as compared to conventional PSL (approximately 4-5 %). Thus, it was concluded that ligand anchored pH sensitive liposome is one of the promising system for the targeted drug therapy in pulmonary tuberculosis.
Nanotechnology-Based Photodynamic Therapy: Concepts, Advances, and Perspectives. - Critical reviews in therapeutic drug carrier systems
Photodynamic therapy (PDT) is a photoactive process that uses the combination of photosensitizers (PSs) and specific wavelengths of light for the treatment of solid tumors and other diseases. PDT received increased attention after regulatory approval of several photosensitizing drugs and light applicators worldwide. With the advent of newer PSs, the role of PDT in the treatment of cancer and other diseases has been revolutionized. In addition, various targeting strategies developed for site-specific delivery of PSs will be helpful for avoiding phototoxicity to normal tissues. Receptor-mediated targeted PDT approaches using nanocarriers offer the opportunity of enhancing photodynamic efficiency by directly targeting diseased cells and tissues. At present, clinical application of PDT is well established in medicine and surgery. Successfully used in dermatology, urology, gastroenterology, and neurosurgery, PDT has also seen much progress in basic sciences and clinical photodynamics in recent years. Currently, the use of PDT is just beginning, and more research must be performed to prove its therapeutic efficacy. However, nontoxic compounds involved in PDT provide a certain hope that it will evolve to be an effective mechanism for combating chronic diseases.
Heteroepitaxial Cu2O thin film solar cell on metallic substrates. - Scientific reports
Heteroepitaxial, single-crystal-like Cu2O films on inexpensive, flexible, metallic substrates can potentially be used as absorber layers for fabrication of low-cost, high-performance, non-toxic, earth-abundant solar cells. Here, we report epitaxial growth of Cu2O films on low cost, flexible, textured metallic substrates. Cu2O films were deposited on the metallic templates via pulsed laser deposition under various processing conditions to study the influence of processing parameters on the structural and electronic properties of the films. It is found that pure, epitaxial Cu2O phase without any trace of CuO phase is only formed in a limited deposition window of P(O2) - temperature. The (00l) single-oriented, highly textured, Cu2O films deposited under optimum P(O2) - temperature conditions exhibit excellent electronic properties with carrier mobility in the range of 40-60â€‰cm(2)â€‰V(-1)â€‰s(-1) and carrier concentration over 10(16)â€‰cm(-3). The power conversion efficiency of 1.65% is demonstrated from a proof-of-concept Cu2O solar cell based on epitaxial Cu2O film prepared on the textured metal substrate.
Collagen nanofiber containing silver nanoparticles for improved wound-healing applications. - Journal of drug targeting
Electrospun nanofibers showing great promise for fabricating nanostructured materials might help to improve the quality of wound care. The present study aimed to investigate the wound-healing potential of collagen nanofiber mats containing silver nanoparticles. Silver nanoparticles (AgNPs) synthesized by the chemical reduction method were incorporated in collagen nanofibers during the electrospinning process. Characterization of electrospun nanofiber mats revealed a mean fiber diameters in the range of 300-700â€‰nm with a sustained release of silver ions shown to follow pseudo-order kinetics. MIC of AgNPs against Staphylococcus aureus and Pseudomonas aeruginosa were evaluated using micro-dilution assay and further antimicrobial activity of fabricated nanofibers was performed. Finally, in vivo studies were performed to demonstrate the wound-healing efficacy of composite nanofibers. In vitro results confirmed the potential antimicrobial efficacy provided by AgNPs and AgNPs composite nanofibers, essential to provide an aseptic environment at the wound site. In vivo study revealed that the rate of wound healing of the composite nanofiber mats was found to be accelerated compared with plain collagen nanofibers. Histology analysis revealed an accelerated re-epithelization, collagen production, and better wound contraction with AgNPs composite collagen nanofibers.
Development and characterization of cefazolin loaded zinc oxide nanoparticles composite gelatin nanofiber mats for postoperative surgical wounds. - Materials science & engineering. C, Materials for biological applications
Systemic antibiotic therapy in post-operative wound care remain controversial leading to escalation in levels of multi-resistant bacteria with unwanted morbidity and mortality. Recently zinc (Zn) because of multiple biophysiological functions, gain considerable interest for wound care. Based on our current understanding, the present study was designed with an intent to produce improve therapeutic approaches for post-operative wound management using composite multi-functional antibiotic carrier. The study involved the fabrication, characterization and pre-clinical evaluation of cefazolin nanofiber mats loaded with zinc oxide (ZnO) and comparing co-formulated mats with individual component, enable a side by side comparison of the benefits of our intervention. Minimum inhibitory concentration (MIC) of the drug, ZnO nanoparticles (ZnONPs) and drug-ZnONP mixture against Staphylococcus aureus was determined using micro dilution assay. The fabricated nanofibers were then evaluated for in-vitro antimicrobial activity and the mechanism of inhibition was predicted by scanning electron microscopy (SEM). Further these nanofiber mats were evaluated in-vivo for wound healing efficacy in Wistar rats. Study revealed that the average diameter of the nanofibers is around 200-900 nm with high entrapment efficiency and display sustained drug release behavior. The combination of ZnO and cefazolin in 1:1 weight ratio showed higher anti-bacterial activity of 1.9 Â± 0.2 Î¼g/ml. Transmission electron microscopy of bacterial cells taken from the zone of inhibition revealed the phenomenon of cell lysis in tested combination related to cell wall disruption. Further composite medicated nanofiber mats showed an accelerated wound healing as compared to plain cefazolin and ZnONP loaded mats. Macroscopical and histological evaluations demonstrated that ZnONP hybrid cefazolin nanofiber showed enhanced cell adhesion, epithelial migration, leading to faster and more efficient collagen synthesis. Hence the fabricated composite nanofiber mats have the potential to be used as a postoperative antimicrobial wound dressings.Copyright Â© 2015. Published by Elsevier B.V.
Development and Characterization of Nanoembedded Microparticles for Pulmonary Delivery of Antitubercular Drugs against Experimental Tuberculosis. - Molecular pharmaceutics
The foremost objective of the present research study was to develop and evaluate the potential of rifampicin (RIF) and isoniazid (INH) loaded spray dried nanoembedded microparticles against experimental tuberculosis (TB). In this study, RIF-INH loaded various formulations (chitosan, guar gum, mannan, and guar gum coated chitosan) were prepared by spray drying and characterized on the basis of in vitro as well as in vivo studies. Results showed that guar gum spray dried particles showed uniform size distribution with smooth surface as compare to mannan formulations. Guar gum batches exhibited excellent flow ability attributed to their optimum moisture content and uniform size distribution. The drug release showed the biphasic pattern of release, i.e., initial burst followed by a sustained release pattern. The preferential uptake of guar gum coated formulations suggested the presence and selective uptake capability of mannose moiety to the specific cell surface of macrophages. In vivo lung distribution study showed that guar gum coated chitosan (GCNP) batches demonstrated prolonged residence at the target site and thereby improve the therapeutic utility of drug with a significant reduction in systemic toxicity. Optimized drug loaded GCNP formulation has resulted in almost 5-fold reduction of the number of bacilli as compared to control group. Histopathology study also demonstrated that none of the treated groups show any evidence of lung tissue abnormality. Hence, GCNPs could be a promising carrier for selective delivery of antitubercular drugs to alveolar macrophages with the interception of minimal side effects, for efficient management of TB.
5th Rib Osteo-pectoralis Major Myocutaneous Flap-Still a Viable Option for Mandibular Defect Reconstruction. - Indian journal of otolaryngology and head and neck surgery : official publication of the Association of Otolaryngologists of India
Reconstruction of mandible is of paramount importance following ablative surgery for oral cancer. Though osteocutaneous micro-vascular free flap is generally accepted to be the mainstay of mandibular reconstruction, other reconstructive options are also done for mandibular reconstruction with good results. Seventeen patients of oral cavity cancer involving the alveolus who had underwent hemi-mandibulectomy were reconstructed using 5th rib osteo-pectoralis major myocutaneous flap. Procedure related pleural tear occurred in 3 patients during harvesting of the rib which were repaired intra-operatively with no post-operative complications. There were 2 failures in our series, in the rest 15 patients the flap had taken up; have good oral continence taking semi-solid diet and have satisfactory cosmetic appearance. This study shows that 5th rib osteo-pectoralis major myocutaneous flap is a quick, easy to learn, one stage reconstructive procedure with a good predictable cosmetic and functional outcomes.
Nano-Systems for Advanced Therapeutics and Diagnosis of Atherosclerosis. - Current pharmaceutical design
Cardiovascular diseases (CVDs) are the leading cause of death and morbidity worldwide. Atherosclerotic situations such as acute myocardial infarction(MI) and stroke are still major causes of death worldwide. Present therapeutic approaches based on conventional drug delivery systems are not efficient to control these disorders. With the technological advancement and intervention of nanotechnology, several fascinating areas are explored for the management of these disorders. Targeted drug delivery approaches and diagnostic tools presented by nanotechnology, certainly took the atherosclerotic disease management to next level. Criticality lies in the rationale selection of an appropriately designed nanocarrier for targeting a specific zone of disease. Manuscript provides a descriptive view of disease targets; nanotechnology based therapeutic and diagnostic approaches and different nanocarriers to accomplish this task. It is important to have the understanding of different classes of these nanosystems along with their specific merits and demerits. Mechanisms and approaches for improving the selectivity or targeting potential are also discussed. There is no doubt that nanotechnology is having great impact in this area, but it is equally important to rationalize its scale up aspects for a real world success.
Spray-dried particles as pulmonary delivery system of anti-tubercular drugs: design, optimization, in vitro and in vivo evaluation. - Pharmaceutical development and technology
Currently, one-third of the world's population is infected with tuberculosis (TB) mainly spread by inhalation of the tubercle bacilli, Mycobacterium tuberculosis. Patient non-compliance is the major reason for failure of anti-tubercular drugs (ATDs) chemotherapy due to multidrug administration for longer duration of time period. The main aim of current research study was to develop and characterize inhalable spray-dried particles for pulmonary delivery of ATDs, i.e., rifampicin (RIF) and isoniazid (INH). ATDs-loaded alginate particles were prepared by ionotropic gelation technique followed by spray drying and characterized on the basis of various evaluation parameters. Results showed that the optimized spray-dried particles were found to be spherical in shape with excellent flow properties. The drug release showed the biphasic pattern of release, i.e., initial burst (30-40% up to 4â€‰h) followed by a sustained release pattern (90% up to 60â€‰h). Optimized formulations exhibited lower cytotoxicity and excellent lung uptake up to 8â€‰h. Optimized formulation also showed higher rate and extent of drug uptake by lungs due to preferential phagocytosis be macrophage. In future, alginate particles could be a promising carrier for targeted delivery of ATDs to alveolar macrophages for efficient management of TB.
Advances in nanotechnology-based carrier systems for targeted delivery of bioactive drug molecules with special emphasis on immunotherapy in drug resistant tuberculosis - a critical review. - Drug delivery
From the early sixteenth and seventeenth centuries to the present day of life, tuberculosis (TB) still is a global health threat with some new emergence of resistance. This type of emergence poses a vital challenge to control TB cases across the world. Mortality and morbidity rates are high due to this new face of TB. The newer nanotechnology-based drug-delivery approaches involving micro-metric and nano-metric carriers are much needed at this stage. These delivery systems would provide more advantages over conventional systems of treatment by producing enhanced therapeutic efficacy, uniform distribution of drug molecule to the target site, sustained and controlled release of drug molecules and lesser side effects. The main aim to develop these novel drug-delivery systems is to improve the patient compliance and reduce therapy time. This article reviews and elaborates the new concepts and drug-delivery approaches for the treatment of TB involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro and nanoemulsion) and some other novel drug-delivery systems for the effective treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for management of MDR-TB and XDR-TB.
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