Sanjeeb K Sahoo

All India Institute of Medical Sciences Bhubaneswar, Bhubaneswar, Orissa, India

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Publications (57)269.69 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Over expression of drug efflux transporters such as P-glycoprotein (P-gp) cumulatively leading to Multidrug resistance (MDR) embodies a major hindrance for successful cancer therapy. A paradigm nanomedicinal approach involving an anticancer drug and modulators of drug resistance within one multifunctional nanocarrier-based delivery system represent an ideal modality for the treatment of MDR. In this regards, we have developed a cationic polymeric nanoparticulate system loaded with MDR1-siRNA and Doxorubicin. Results indicated augmented synergistic effect of combinational nanoformulation in overcoming MDR in MCF-7/ADR cells. Therefore, the above regime could be a promising co-delivery system for effective therapy of drug resistant breast cancer.
    International Journal of Pharmaceutics 08/2014; · 3.99 Impact Factor
  • Abhalaxmi Singh, Sanjeeb K Sahoo
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    ABSTRACT: Multifunctional nanoplatforms represent a cutting edge tool in biomedical applications as a result of their applicability in the concurrent monitoring of medical treatment. Magnetic nanoparticles (MNPs) have generated great interest in the field of cancer nanotheranostics owing to their intrinsic magnetic property that enables them to be used as contrast agents in magnetic resonance imaging and as a therapeutic system in conjunction with hyperthermia. In addition, the physical properties and biocompatibility of MNPs help them to act as efficient drug carriers for targeted therapeutic regimes. In this review, we have discussed the different theranostic applications of MNPs. Further, we have raised the current challenges associated with the clinical translation of MNPs along with future opportunities in this field.
    Drug discovery today 10/2013; · 6.63 Impact Factor
  • Fahima Dilnawaz, Sanjeeb Kumar Sahoo
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    ABSTRACT: Glioblastomas (GBMs) are highly lethal primary brain tumors. Treatment of these malignant gliomas remains ineffective as these are extremely resistant to chemotherapeutic applications. Furthermore, combination therapy for cancer treatment is becoming more popular because it generates synergistic anticancer effects, by reducing individual drug-related toxicity and associated side effects. Currently, magnetic nanoparticles (MNPs), based drug delivery system has attracted much more attention owing to its intrinsic magnetic properties and drug loading capacity. In the present study, MNPs based drug delivery approach for co- delivering of potent chemotherapeutic drugs such as Curcumin (herbal drug) and Temozolomide (DNA methylating agent) has been implemented. The dual drug loaded MNPs formulations were evaluated in two dimensional (2-D) monolayer culture and three-dimensional (3-D) tumour spheroid culture of T-98G cells for understanding the therapeutic discrepancy. The dual drug loaded MNPs formulations demonstrated higher cytotoxic effect than single drug loaded MNPs formulations as compared to their corresponding native drugs in 2-D and 3-D culture. The combination index (CI) analysis revealed synergistic mode of action of dual drug loaded MNPs formulations, which was further confirmed by cell death induction assay mediated by acridine orange (AO) / propidium iodide (PI) staining, illustrating higher efficacy of the formulation towards GBM therapy.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 07/2013; · 3.15 Impact Factor
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    Priyambada Parhi, Chandana Mohanty, Sanjeeb Kumar Sahoo
    Acta biomaterialia 06/2013; 9(6):7078. · 5.09 Impact Factor
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    ABSTRACT: This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. Due to highly unethical practices, which include serial self plagiarism, data manipulation and falsification of results found across multiple papers in Acta Biomaterialia. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.
    Acta biomaterialia 06/2013; 9(6):7075. · 5.09 Impact Factor
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    Manasi Das, Sanjeeb K Sahoo
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    ABSTRACT: This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. Due to highly unethical practices, which include serial self plagiarism, data manipulation and falsification of results found across multiple papers in Acta Biomaterialia. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.
    Acta biomaterialia 06/2013; 9(6):7076. · 5.09 Impact Factor
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    Fahima Dilnawaz, Abhalaxmi Singh, Sanjeeb Kumar Sahoo
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    ABSTRACT: This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. Due to highly unethical practices, which include serial self plagiarism, data manipulation and falsification of results found across multiple papers in Acta Biomaterialia. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.
    Acta biomaterialia 06/2013; 9(6):7077. · 5.09 Impact Factor
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    Paromita Kundu, Chandana Mohanty, Sanjeeb K Sahoo
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    ABSTRACT: This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. Due to highly unethical practices, which include serial self plagiarism, data manipulation and falsification of results found across multiple papers in Acta Biomaterialia. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.
    Acta biomaterialia 06/2013; 9(6):7074. · 5.09 Impact Factor
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    ABSTRACT: In spite of intense research efforts, pancreatic ductal adenocarcinoma remains one of the most deadly malignancies in the world. We and others have previously identified a subpopulation of pancreatic cancer stem cells within the tumor as a critical therapeutic target and additionally shown that the tumor stroma represents not only a restrictive barrier for successful drug delivery, but also serves as a paracrine niche for cancer stem cells. Therefore, we embarked on a large-scale investigation on the effects of combining chemotherapy, hedgehog pathway inhibition, and mTOR inhibition in a preclinical mouse model of pancreatic cancer. Prospective and randomized testing in a set of almost 200 subcutaneous and orthotopic implanted whole-tissue primary human tumor xenografts. The combined targeting of highly chemoresistant cancer stem cells as well as their more differentiated progenies, together with abrogation of the tumor microenvironment by targeting the stroma and enhancing tissue penetration of the chemotherapeutic agent translated into significantly prolonged survival in preclinical models of human pancreatic cancer. Most pronounced therapeutic effects were observed in gemcitabine-resistant patient-derived tumors. Intriguingly, the proposed triple therapy approach could be further enhanced by using a PEGylated formulation of gemcitabine, which significantly increased its bioavailability and tissue penetration, resulting in a further improved overall outcome. This multimodal therapeutic strategy should be further explored in the clinical setting as its success may eventually improve the poor prognosis of patients with pancreatic ductal adenocarcinoma.
    PLoS ONE 01/2013; 8(6):e66371. · 3.73 Impact Factor
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    Biomaterials 11/2012; 33(33):8743–8744. · 8.31 Impact Factor
  • Chandana Mohanty, Manasi Das, Sanjeeb K Sahoo
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    ABSTRACT: Introduction: Curcumin is a safe, affordable and natural bioactive molecule of turmeric (Curcuma longa). It has gained considerable attention in recent years for its multiple pharmacological activities. However, its optimum pharmaceutical potential has been limited by its lack of aqueous solubility and poor bioavailability. To mitigate the above limitations, recently various nanostructured water-soluble delivery systems were developed to increase the solubility and bioavailability of curcumin. Areas covered: Major reasons contributing to the low bioavailability of curcumin appear to be owing to its poor solubility, low absorption, rapid metabolism and rapid systemic elimination. The present review summarizes the strategies using curcumin in various nanocarrier delivery systems to overcome poor solubility and inconsistent bioavailability of curcumin and describes the current status and challenges for the future. Expert opinion: The development of various drug delivery systems to deliver curcumin will certainly provide a step up towards augmenting the therapeutic activity of curcumin thereby increasing the solubility and bioavailability of curcumin. However, the future of such delivery technology will be highly dependent on the development of safe, non-toxic and non-immunogenic nanocarriers.
    Expert Opinion on Drug Delivery 09/2012; 9(11):1347-64. · 4.87 Impact Factor
  • Chandana Mohanty, Manasi Das, Sanjeeb K Sahoo
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    ABSTRACT: Wound healing is an intricate multistage process that includes inflammation, cell proliferation, matrix deposition and remodeling phases. It is often associated with oxidative stress and consequent prolonged inflammation, resulting in impaired wound healing. Curcumin has been reported to improve wound healing in different animal models. In order to increase the efficacy of curcumin in the healing arena a curcumin loaded oleic acid based polymeric (COP) bandage was formulated. The in vivo wound healing potency was compared with void bandage and control (cotton gauze treatment) in a rat model. Biochemical parameters and histological analysis revealed increased wound reduction and enhanced cell proliferation in COP bandage treated groups due to its efficient free radical scavenging properties. Comparative acceleration in wound healing was due to early implementation of fibroblasts and its differentiation (increased level of α-smooth muscle actin). Western blotting and semiquantitative PCR analysis clearly indicate that COP bandage can efficiently quench free radicals leading to reduced antioxidative enzyme activity. Further evidence at mRNA and protein level indicates that our system is potent enough to reduce the inflammatory response mediated by the NFκB pathway during wound healing. With this background, we anticipate that such a versatile approach may seed new arena for topical wound healing in the near future.
    Molecular Pharmaceutics 09/2012; 9(10):2801-11. · 4.57 Impact Factor
  • Mallaredy Vandana, Sanjeeb K Sahoo
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    ABSTRACT: Pemetrexed has been widely used as an effective chemotherapeutic agent for the treatment of a variety of cancers including breast cancer. It is a multitargeted antifolate that gets transported to cells primarily by reduced folate carrier (RFC) and exerts its action by disrupting folate-dependent metabolic processes essential for cell replication. The loss of RFC leads to impaired transport of pemetrexed, which in turn decreases its intracellular concentration and reduces its cytotoxic effect on cancer cells. Furthermore, the multidrug resistance (MDR) related proteins (MRPs) contribute to pemetrexed efflux from the cancer cells. These observations prompted us to develop PEGylated pemetrexed that follows an efficient cellular internalization route independent of RFC and simultaneously bypasses the MRP efflux mechanism for acting as an efficient chemotherapeutic agent. Thus, the present study focuses on PEGylation of pemetrexed for its superior therapeutic efficiency by evaluating its cellular uptake and retention by flow cytometry, confocal microscopy, and reversed-phase high-performance liquid chromatography (RP-HPLC) in breast cancer cell lines having RFC expression and lacking RFC expression, that is, MCF7 and MDA MB231, respectively. In addition, the treatment of PEGylated pemetrexed lead to enhanced cytotoxicity due to S-phase arrest and apoptosis in the above mentioned cell lines. Interestingly, the longer circulation time of PEGylated pemetrexed in animal model concomitant with the RFC independent uptake and enhanced cytotoxicity suggests it to be a potential candidate for cancer therapy in a clinical setting.
    Molecular Pharmaceutics 08/2012; 9(10):2828-43. · 4.57 Impact Factor
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    ABSTRACT: Osteoporosis is a condition of bone loss due to excessive osteoclastic activity. Several protein factors, such as receptor activator of nuclear factor kappa-B (RANK), receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), have been identified that are important in the pathogenesis of osteoporosis. RANKL binds to RANK and activates the NF-κB pathway by interaction of its cytoplasmic domain with an intracellular adapter protein, TNF receptor associated factors 6 (TRAF 6). This interaction can be inhibited by cell-permeable peptides that prevent RANK-TRAF 6 interaction. However, similar to the peptides/proteins used in clinical setting, the effective application of this TRAF 6 Inhibitory peptide as a therapeutic agent is marred by several limitations for instance short half-life, rapid renal clearance and immunogenicity. In the present study, we have developed PEGylated TRAF 6 Inhibitory peptide by conjugating TRAF 6 Inhibitory peptide to linear PEG backbone that exhibits longer bioavailability in plasma in the animal model. Besides, it has an enhanced uptake at its site of action, i.e., bone marrow.
    International Journal of Pharmaceutics 06/2012; 434(1-2):429-36. · 3.99 Impact Factor
  • Priyambada Parhi, Chandana Mohanty, Sanjeeb Kumar Sahoo
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    ABSTRACT: Combination therapy for the treatment of cancer is becoming more popular because it generates synergistic anticancer effects, reduces individual drug-related toxicity and suppresses multi-drug resistance through different mechanisms of action. In recent years, nanotechnology-based combination drug delivery to tumor tissues has emerged as an effective strategy by overcoming many biological, biophysical and biomedical barriers that the body stages against successful delivery of anticancer drugs. The sustained, controlled and targeted delivery of chemotherapeutic drugs in a combination approach enhanced therapeutic anticancer effects with reduced drug-associated side effects. In this article, we have reviewed the scope of various nanotechnology-based combination drug delivery approaches and also summarized the current perspective and challenges facing the successful treatment of cancer.
    Drug discovery today 05/2012; 17(17-18):1044-52. · 6.63 Impact Factor
  • Paromita Kundu, Chandana Mohanty, Sanjeeb K Sahoo
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    ABSTRACT: Glioblastoma, the most aggressive form of brain and central nervous system tumours, is characterized by high rates proliferation, migration and invasion. The major road block in the delivery of drugs to the brain is the blood-brain barrier, along with the expression of various multi-drug resistance (MDR) proteins that cause the efflux of a wide range of chemotherapeutic drugs. Curcumin, a herbal drug, is known to inhibit cellular proliferation, migration and invasion and induce apoptosis of glioma cells. It also has the potential to modulate MDR in glioma cells. However, the greatest challenge in the administration of curcumin stems from its low bioavailability and high rate of metabolism. To circumvent the above pitfalls of curcumin we have developed curcumin-loaded glyceryl monooleate (GMO) nanoparticles (NP) coated with the surfactant Pluronic F-68 and vitamin E D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) for brain delivery. We demonstrated that our curcumin-loaded NPs inhibit cellular proliferation, migration and invasion along with a higher percentage of cell cycle arrest and telomerase inhibition, thus leading to a greater percentage apoptotic cell death in glioma cells compared with native curcumin. An in vivo study demonstrated enhanced bioavailability of curcumin in blood serum and brain tissue when delivered by curcumin-loaded GMO NPs compared with native curcumin in a rat model. Thus, curcumin-loaded GMO NPs can be used as an effective delivery system to overcome the challenges of drug delivery to the brain, providing a new approach to glioblastoma therapy.
    Acta biomaterialia 04/2012; 8(7):2670-87. · 5.09 Impact Factor
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    ABSTRACT: There is much interest in utilizing the intrinsic properties of magnetic nanoparticles (MNPs) for the theranostic approaches in medicine. With an aim to develop a potential therapeutics for glioma treatment, efficacy of aqueous dispersible paclitaxel loaded MNPs (Pac-MNPs) were studied in glioblastoma cell line (U-87). The identified potential receptor, glycoprotein non-metastatic melanoma protein B (GPNMB) overexpressed by glioblastoma cells, was actively targeted using GPNMB conjugated Pac-MNPs in U-87 cells. As blood brain barrier (BBB) is the primary impediment in the treatment of glioblastoma, therefore, an attempt was taken to evaluate the biodistribution and brain uptake of Pac-MNPs in rats. The bioavailability of Pac-MNPs illustrated a prolonged blood circulation in vivo, which demonstrated the presence of significant amounts of drug in rat brain tissues as compared to native paclitaxel. Further, the transmission electron microscopy (TEM) study revealed significant accumulation of the Pac-MNPs in the brain tissues. Being an effective contrast enhancement agent for magnetic resonance imaging (MRI) at tissue levels, the MNPs devoid of any surfactant demonstrated enhanced contrast effect in liver and brain imaging. Hence, the significant prevalence of drugs in the rat brain tissues, in vitro targeting potentiality as well as the augmented contrast effect elicit the non-invasive assessment and theranostic applications of MNPs for brain tumor therapy.
    Biomaterials 04/2012; 33(10):2936-51. · 8.31 Impact Factor
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    Manasi Das, Sanjeeb K Sahoo
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    ABSTRACT: Retinoblastoma is the most common intraocular tumor in children. Malfunctioning of many signaling pathways regulating cell survival or apoptosis, make the disease more vulnerable. Notably, resistance to chemotherapy mediated by MRP-1, lung-resistance protein (LRP) is the most challenging aspect to treat this disease. Presently, much attention has been given to the recently developed anticancer drug nutlin-3a because of its non-genotoxic nature and potency to activate tumor suppressor protein p53. However, being a substrate of multidrug resistance protein MRP1 and Pgp its application has become limited. Currently, research has step towards reversing Multi drug resistance (MDR) by using curcumin, however its clinical relevance is restricted by plasma instability and poor bioavailability. In the present investigation we tried to encapsulate nutlin-3a and curcumin in PLGA nanoparticle (NPs) surface functionalized with folate to enhance therapeutic potential of nutlin-3a by modulating MDR. We document that curcumin can inhibit the expression of MRP-1 and LRP gene/protein in a concentration dependent manner in Y79 cells. In vitro cellular cytotoxicity, cell cycle analysis and apoptosis studies were done to compare the effectiveness of native drugs (single or combined) and single or dual drug loaded nanoparticles (unconjugated/folate conjugated). The result demonstrated an augmented therapeutic efficacy of targeted dual drug loaded NPs (Fol-Nut-Cur-NPs) over other formulation. Enhanced expression or down regulation of proapoptotic/antiapoptotic proteins respectively and down-regulation of bcl2 and NFκB gene/protein by Fol-Nut-Cur-NPs substantiate the above findings. This is the first investigation exploring the role of curcumin as MDR modulator to enhance the therapeutic potentiality of nutlin-3a, which may opens new direction for targeting cancer with multidrug resistance phenotype.
    PLoS ONE 01/2012; 7(3):e32920. · 3.73 Impact Factor
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    ABSTRACT: Novel strategies are being applied for creating better in vitro models that simulate in vivo conditions for testing the efficacy of anticancer drugs. In the present study we developed surface-engineered, large and porous, biodegradable, polymeric microparticles as a scaffold for three dimensional (3-D) growth of a Y79 retinoblastoma (RB) cell line. We evaluated the effect of three anticancer drugs in naïve and nanoparticle-loaded forms on a 3-D versus a two-dimensional (2-D) model. We also studied the influence of microparticles on extracellular matrix (ECM) synthesis and whole genome miRNA-gene expression profiling to identify 3D-responsive genes that are implicated in oncogenesis in RB cells. Poly(D,L)-lactide-co-glycolide (PLGA) microparticles were prepared by the solvent evaporation method. RB cell line Y79 was grown alone or with PLGA-gelatin microparticles. Antiproliferative activity, drug diffusion, and cellular uptake were studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a yellow tetrazole (MTT) assay, fluorescent microscope, and flow cytometry. Extra cellular matrix (ECM) synthesis was observed by collagenase assay and whole genome miRNA-microarray profiling by using an Agilent chip. With optimized composition of microparticles and cell culture conditions, an eightfold increase from the seeding density was achieved in 5 days of culture. The antiproliferative effect of the drugs in the 3-D model was significantly lower than in the 2-D suspension, which was evident from the 4.5 to 21.8 fold differences in their IC(50) values. Using doxorubicin, the flow cytometry data demonstrated a 4.4 fold lower drug accumulation in the cells grown in the 3-D model at 4 h. The collagen content of the cells grown in the 3-D model was 2.3 fold greater than that of the cells grown in the 2-D model, suggesting greater synthesis of the extracellular matrix in the 3-D model as the extracellular matrix acted as a barrier to drug diffusion. The microarray and miRNA analysis showed changes in several genes and miRNA expression in cells grown in the 3-D model, which could also influence the environment and drug effects. Our 3-D retinoblastoma model could be used in developing effective drugs based on a better understanding of the role of chemical, biologic, and physical parameters in the process of drug diffusion through the tumor mass, drug retention, and therapeutic outcome.
    Molecular vision 01/2012; 18:1361-78. · 1.99 Impact Factor
  • Ranjita Misra, Sanjeeb K Sahoo
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    ABSTRACT: Doxycycline is a tetracycline antibiotic with a potent antibacterial activity against a wide variety of bacteria. However, poor cellular penetration limits its use for the treatment of infectious disease caused by intracellular pathogens. One potential strategy to overcome this problem is the use of nanotechnology that can help to easily target the intracellular sites of infection. The antibacterial activity of these antibiotics is enhanced by encapsulating it in polymeric nanoparticles. In this study, we describe the improvement of the entrapment efficiency of doxycycline hydrochloride (doxycycline)-loaded PLGA:PCL nanoparticles up to 70% with variation of different formulation parameters such as polymer ratio, amount of drug loading (w/w), solvent selection, electrolyte addition, and pH alteration in the formulation. We have evaluated the efficacy of these nanoparticles over native doxycycline against a strain of Escherichia coli (DH5α) through growth inhibition and colony counting. The results indicate that doxycycline-loaded nanoparticles have superior effectiveness compared to native doxycycline against the above bacterial strain, resulting from the sustained release of doxycycline from nanoparticles. These results are encouraging for the use of these doxycycline-loaded nanoparticles for the treatment of infections caused by doxycycline-sensitive bacteria.
    Methods in enzymology 01/2012; 509:61-85. · 1.90 Impact Factor