Andrographolide nanoparticles in leishmaniasis: characterization and in vitro evaluations.
TL;DR: Antileishmanial activity was found to be significant for the nanoparticle preparation with 4% PVA in about one-fourth of the dosage of the pure compound AG (IC50 160 μM), which have significant potential to target the infested macrophage cells and prove valuable in chemotherapy of neglected tropical diseases such as leishmaniasis.
Abstract: Andrographolide (AG) is a diterpenoid lactone isolated from the leaves of Andrographis paniculata. AG is a potent and low-toxicity antileishmanial agent. Chemotherapy applications of AG are, however, seriously constrained because of poor bioavailability, short plasma half-life, and inappropriate tissue localization. Nanoparticulation of AG was therefore envisaged as a possible solution. AG nanoparticles (AGnp) loaded in 50:50 poly(DL-lactide-co-glycolic acid) were prepared for delivery into the monocyte-macrophage cells infested with the amastigote form of leishmanial parasite for evaluation in the chemotherapy of leishmaniasis. Particle characteristics of AGnp were optimized by proportionate application of a stabilizer, polyvinyl alcohol (PVA). Physicochemical characterization of AGnp by photon correlation spectroscopy exhibited an average particle size of 173 nm and zeta potential of -34.8 mV. Atomic force microscopy visualization revealed spherical nanoparticles with a smooth surface. Antileishmanial activity was found to be significant for the nanoparticle preparation with 4% PVA (IC₅₀) 34 μM) in about one-fourth of the dosage of the pure compound AG (IC₅₀) 160 μM). AGnp therefore have significant potential to target the infested macrophage cells and prove valuable in chemotherapy of neglected tropical diseases such as leishmaniasis.
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TL;DR: In this paper, a solution enhanced dispersion by supercritical fluids (SEDS) was applied for the production of lutein/zein nanoparticles and the effects of the process variables on the morphology, drug loading, entrapment efficiency, and mean particle size of the nanoparticles were investigated.
Abstract: Solution enhanced dispersion by supercritical fluids (SEDS) was applied for the production of lutein/zein nanoparticles. The effects of the process variables on the morphology, drug loading, entrapment efficiency, and mean particle size of the nanoparticles were investigated. The results showed that the nanoparticles with high drug loading and high entrapment efficiency were prepared by SEDS process. Temperature, pressure, ratio of lutein/zein, and solution flow rate can influence the morphology, drug loading, entrapment efficiency, and the mean particle size of the lutein/zein nanoparticles. The lower temperature and solution flow rate coupled with high pressure, favor smaller and more regular spheres. The initial and overall drug release behavior of the samples was tested. The initial burst release was hardly observed in the nanoparticles processed at 45 °C/10 MPa. Furthermore, lutein release profile displayed a near zero-order release, which implied that the nanoparticles played a role in controlled release of lutein.
165 citations
TL;DR: The present article covers antiviral properties of andrographolide in variety of viral infections, with the hope of developing of a new highly potent antiviral drug with multiple effects.
Abstract: Andrographolide, a diterpenoid, is known for its anti-inflammatory effects. It can be isolated from various plants of the genus Andrographis, commonly known as 'creat'. This purified compound has been tested for its anti-inflammatory effects in various stressful conditions, such as ischemia, pyrogenesis, arthritis, hepatic or neural toxicity, carcinoma, and oxidative stress, Apart from its anti-inflammatory effects, andrographolide also exhibits immunomodulatory effects by effectively enhancing cytotoxic T cells, natural killer (NK) cells, phagocytosis, and antibody-dependent cell-mediated cytotoxicity (ADCC). All these properties of andrographolide form the foundation for the use of this miraculous compound to restrain virus replication and virus-induced pathogenesis. The present article covers antiviral properties of andrographolide in variety of viral infections, with the hope of developing of a new highly potent antiviral drug with multiple effects.
120 citations
TL;DR: New quercetin conjugated gold nanoparticles (QAunp) were successfully evaluated for the first time against leishmanial macrophage infections.
Abstract: Gold nanoparticles (Aunp) through biogenetic processes have induced enormous interest for lower toxicity and precise applications. A rapid, one pot synthesis for uniformly sized gold nanoparticles was developed using polyphenolic compound quercetin. Reduction process was followed at low temperatures in a simple bath type sonicator. Nanoparticle plasmon response was recorded at 540 nm and the average size in TEM was observed at 15.07 nm. Detailed X-ray diffraction (XRD) observations proved fcc crystalline structure of metallic gold and the Fourier transform infrared (FTIR) analysis has confirmed nanoparticles conjugation with quercetin. Leishmaniasis, is a neglected tropical disease (NTD) classified by the World Health Organization (WHO). The leishmanial parasite multiply in host macrophages and most strains have developed drug resistance to available chemotherapeutics. Drug delivery is therefore a major problem in macrophage specific leishmanial parasite infections. New quercetin conjugated gold nanoparticles (QAunp) were successfully evaluated for the first time against leishmanial macrophage infections. Antileishmanial efficiency of QAunp was established against wild type (IC50 15±3), sodium stibogluconate resistant strain (IC50 40±8) and the paramomycin resistant (IC50 30±6) strains. Macrophage uptake of QAunp was complete within an hour as observed in TEM experiments.
104 citations
TL;DR: Some of the recent advances in the nanotechnological research regarding the treatment of leishmaniasis are presented and further efforts will still be necessary for this therapy to have greater clinical applicability in humans.
Abstract: Leishmaniasis, a vector-borne disease caused by obligate intramacrophage protozoa, threatens 350 million people in 98 countries around the world. There are already 12 million infected people worldwide and two million new cases occur annually. Leishmaniasis has three main clinical presentations: cutaneous (CL), mucosal (ML), and visceral (VL). It is considered an opportunistic, infectious disease and the HIV-leishmaniasis correlation is well known. Antimonial compounds are used as first-line treatment drugs, but their toxicity, which can be extremely high, leads to a number of undesirable side effects and resultant failure of the patients to adhere to treatment. There is also a reported increase in Leishmania sp. resistance to these drugs. Nanotechnology has emerged as an attractive alternative because of its improved bioavailability and lower toxicity, and other characteristics that help to relieve the burden of this disease. In this review we will present some of the recent advances in the nanotechnological research regarding the treatment of leishmaniasis. The preclinical results regarding the approaches for a biomedical treatment of the disease have been encouraging, but further efforts will still be necessary for this therapy to have greater clinical applicability in humans.
94 citations
TL;DR: The mechanisms of classical drug resistance and potential drug targets in Leishmania infection are described and the current drug-delivery systems and future perspectives towards Leishmaniasis treatment are covered.
Abstract: Leishmaniasis is a complex of diseases with numerous clinical manifestations for instance harshness from skin lesions to severe disfigurement and chronic systemic infection in the liver and spleen. So far, the most classical leishmaniasis therapy, despite its documented toxicities, remains pentavalent antimonial compounds. The available therapeutic modalities for leishmaniasis are overwhelmed with resistance to leishmaniasis therapy. Mechanisms of classical drug resistance are often related with the lower drug uptake, increased efflux, the faster drug metabolism, drug target modifications and over-expression of drug transporters. The high prevalence of leishmaniasis and the appearance of resistance to classical drugs reveal the demand to develop and explore novel, less toxic, low cost and more promising therapeutic modalities. The review describes the mechanisms of classical drug resistance and potential drug targets in Leishmania infection. Moreover, current drug-delivery systems and future perspectives towards Leishmaniasis treatment are also covered.
75 citations
References
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01 Jan 1962
TL;DR: In this article, the authors present a survey of research work in physics, physical sciences, and physical chemistry, focusing on physics, chemistry, physics, and biology. But they do not discuss their work in this paper.
Abstract: This book should be of interest to senior undergraduates, postgraduates and research workers in physics, physical sciences, physical chemistry.
8,754 citations
TL;DR: In this article, the role of dynamic swelling and the dissolution of the polymer matrix on the release mechanism was discussed, as well as the effect of the tracer/excipient ratio on the poly(vinyl alcohol) release profile.
Abstract: Porous hydrophilic discs were prepared from two grades of poly(vinyl alcohol) of varying degree of hydrolysis. The influence of the molecular size of the tracer used (potassium chloride, phenylpropanolamine hydrochloride and bovine serum albumin), that of the addition of a second water-soluble polymer poly(N-vinyl-2-pyrrolidone) and poly(ethylene glycol)) and the effect of the tracer/excipient ratio on the release profile were examined. Finally the role of the dynamic swelling and the dissolution of the polymer matrix on the release mechanism are discussed.
4,397 citations
TL;DR: It is highly feasible for nanoparticles of biodegradable polymers to be applied to promote oral chemotherapy by using Caco-2 cells, showing that surface modification of PLGA nanoparticles with vitamin E TPGS notably improved the cellular uptake.
Abstract: This study evaluated cellular uptake of polymeric nanoparticles by using Caco-2 cells, a human colon adenocarcinoma cell line, as an in vitro model with the aim to apply nanoparticles of biodegradable polymers for oral chemotherapy The feasibility was demonstrated by showing the localization and quantification of the cell uptake of fluorescent polystyrene nanoparticles of standard size and poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated with polyvinyl alcohol (PVA) or vitamin E TPGS Coumarin-6 loaded PLGA nanoparticles were prepared by a modified solvent extraction/evaporation method and characterized by laser light scattering for size and size distribution, scanning electron microscopy (SEM) for surface morphology, zeta-potential for surface charge, and spectrofluorometry for fluorescent molecule release from the nanoparticles The effects of particle size and particle surface coating on the cellular uptake of the nanoparticles were quantified by spectrofluorometric measurement Cellular uptake of vitamin E TPGS-coated PLGA nanoparticles showed 14 folds higher than that of PVA-coated PLGA nanoparticles and 4-6 folds higher than that of nude polystyrene nanoparticles Images of confocal laser scanning microscopy, cryo-SEM and transmission electron microscopy clearly evidenced the internalization of nanoparticles by the Caco-2 cells, showing that surface modification of PLGA nanoparticles with vitamin E TPGS notably improved the cellular uptake It is highly feasible for nanoparticles of biodegradable polymers to be applied to promote oral chemotherapy
1,354 citations
"Andrographolide nanoparticles in le..." refers background in this paper
...Nanoparticle cellular uptake is markedly dependent on size and surface charge.(30) Nanoparticles in a size range below 200 nm are associated with increased phagocytosis and can easily localize in macrophages predominantly infested with leishmanial parasite....
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TL;DR: Important findings of the past decade on the encapsulation and release profiles of macromolecular therapeutics from PLGA and PLGA-based nano/microparticles are discussed critically in relation to nature and type of bioactive molecule, carrier polymer and experimental variables that influence the delivery of macrochemical therapeutics.
Abstract: Biodegradable nano/microparticles of poly(D,L-lactide-co-glycolide) (PLGA) and PLGA-based polymers are widely explored as carriers for controlled delivery of macromolecular therapeutics such as proteins, peptides, vaccines, genes, antigens, growth factors, etc. These devices are mainly produced by emulsion or double-emulsion technique followed by solvent evaporation or spray drying. Drug encapsulation, particle size, additives added during formulation, molecular weight, ratio of lactide to glycolide moieties in PLGA and surface morphology could influence the release characteristics. Encapsulation efficiency and release rates through nano/microparticle-mediated drug delivery devices can be optimized to improve their therapeutic efficacy. In this review, important findings of the past decade on the encapsulation and release profiles of macromolecular therapeutics from PLGA and PLGA-based nano/microparticles are discussed critically in relation to nature and type of bioactive molecule, carrier polymer and experimental variables that influence the delivery of macromolecular therapeutics. Even though extensive research on biodegradable microparticles containing macromolecular drugs has greatly advanced to the level of production know-how, the effects of critical parameters influencing drug encapsulation are not sufficiently investigated for nano-scaled carriers. The present review attempts to address some important data on nano/microparticle-based delivery systems of PLGA and PLGA-derived polymers with reference to macromolecular drugs.
999 citations