Nanoprecipitation Technique Research Articles

Enhanced tumor uptake, biodistribution and pharmacokinetics of etoposide loaded nanoparticles in Dalton′s lymphoma tumor bearing mice

Background:Nanotechnology plays a remarkable role in the field of the treatment of Lymphomas associated with tumor.Objective:The purpose of this study is to determine and to compare the tumor uptake, biodistribution and pharmacokinetics of radiolabeled etoposide and etoposide loaded nanoparticles in Dalton's Lymphoma tumor bearing mice and healthy mice.Materials and Methods:Etoposide loaded nanoparticles were prepared by nanoprecipitation technique using the poly (lactic-co-glycolic) acid (PLGA) in the presence of Pluronic F 68 (F 68) as a stabilizer and characterized by particle size analyzer, zeta potential and transmission electron microscope. Etoposide and etoposide loaded nanoparticles were labeled with Technetium-99m (Tc-99m) by the direct method and various quality control tests were carried out. The labeling parameters like labeling efficiency, stability, etc., were optimized to get high labeling efficiency as well as stability of the labeled formulations. Tc-99m labeled formulations were administered intravenously in Balb C mice and their biodistribution and pharmacokinetics were determined.Results:Mean size of the etoposide loaded PLGA nanoparticles was found to be 105.1 nm. The concentration of both free etoposide and nanoparticles increased with time and showed higher tumor concentrations of both free etoposide and nanoparticles increased with time and showed higher retention, indicating their applicability in effective and prolonged tumor therapy. Nuclear scintigraphic images confirm the presence of labeled complexes at the site of tumor for 24 h at higher concentration than in the normal muscles.Conclusion:This study indicated higher tumor affinity and targeting properties of etoposide loaded nanoparticles than free etoposide.

Pyrimethamine nanosuspension with improved bioavailability: in vivo pharmacokinetic studies.

Pyrimethamine is a standard antiprotozoal drug recommended for prophylaxis and treatment of malarial infections. Limited bioavailability, slow onset of action, and life-threatening side effects restrict its use. Hence, in the present study, pyrimethamine nanosuspension was prepared with the objective to improve its dissolution rate and pharmacokinetic profile. Stable pyrimethamine nanosuspension with submicron particle size was prepared by nanoprecipitation and high-pressure homogenization techniques. Nanosizing and stabilizers modified the surface characteristics of drug particles resulting in considerable increase in the dissolution rate. The in vivo pharmacokinetic studies of the prepared nanosuspension were carried out and compared with plain pyrimethamine suspension and marketed pyrimethamine suspension. The in vivo pharmacokinetic profiling of pyrimethamine nanosuspension in rats showed higher AUC0-24h and C max compared to the plain and marketed pyrimethamine suspensions. In contrast to its plain and marketed formulation, pyrimethamine nanosuspension showed rapid onset of action (T max 0.5h vs. 2h). Also, the low volume of distribution and reduced elimination half-life of the developed nanosuspension can lead to reduced side effects. Thus, improved in vitro-in vivo kinetics indicated that nanosuspension proved to be a suitable strategy for elevating the therapeutic profile of pyrimethamine.

Comparative Receptor Based Brain Delivery of Tramadol-Loaded Poly(lactic-co-glycolic acid) Nanoparticles

Receptor mediated endocytosis or transcytosis has been reported for drug delivery across Blood-brain barrier (BBB) and hence, the aim of the present investigations was to prepare and compare brain targeting efficiency of tramadol-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles surface modified with transferrin (Tf) and lactoferrin (Lf). Nanoparticles of tramadol were prepared using nanoprecipitation technique and surface conjugated with Tf and Lf using epoxy linker. Prepared nanoparticles were characterized for their size, surface charge, drug entrapment, transmission electron microscopy and in vitro drug release. The surface density of Tf and Lf was estimated by protein estimation. The drug distribution in blood, brain and other tissues was studied in mice after intravenous administration. Tf and Lf anchored nanoparticles exhibit enhanced uptake with 2.38 and 3.85 folds higher targeting respectively in the brain when compared with unconjugated nanoparticles. The brain targeting observed for Lf anchored PLGA nanoparticles (Lf-TMD-PLGA-NP) was 1.62 folds that of Tf anchored PLGA nanoparticles (Tf-TMD-PLGA-NP). Hence, the study revealed Tf and specially Lf as promising ligand for enhanced brain deposition of tramadol.

Phytosomes Loaded with Mitomycin C–Soybean Phosphatidylcholine Complex Developed for Drug Delivery

A novel formulation system of phytosomes loaded with mitomycin C-soybean phosphatidylcholine (MMC-SPC) complex (MMC-loaded phytosomes) was prepared by a solvent evaporation method combined with a nanoprecipitation technique for the purpose of development of an MMC drug delivery system. The MMC-loaded phytosomes were evaluated by average particle size, zeta-potential, and residual drug-loading content as well as an in vitro drug release profile. Furthermore, in vitro stability tests and in vitro/vivo biological evaluations of the MMC-loaded phytosomes were performed. DSC, FTIR, and XRD demonstrated that MMC interacted physically with SPC within the phytosomes. DLS and ELS described a dispersion with an average particle size of 210.87 nm, a narrow size distribution (PDI 0.251), and a zeta-potential of -33.38 mV. SEM, TEM, and AFM images showed that the MMC-loaded phytosomes were spherical and intact vesicles. In vitro stability tests demonstrated that the average particle size and residual drug-loading content of the MMC-loaded phytosomes had no evident change at different storage conditions. In vitro drug release profiles indicated biphasic behavior with an initial burst release, followed by a subsequent prolonged sustained release. In vitro cytotoxicity assays with H(22) cells showed that the MMC-loaded phytosomes had remarkable cytotoxicity. In vivo antitumor effect of the MMC-loaded phytosomes also revealed a dose-dependent and superior curative inhibitory effect on tumor growth without loss of body weight compared to free MMC. Histopathological analysis of specimens taken from tumor tissues indicated that MMC-loaded phytosomes had lethal effect to hepatoma cell. These findings suggested that the MMC-loaded phytosomes can serve as a promising and effective formulation for drug delivery and cancer therapy.

Carbon Nanotube: A Novel Carrier for Sustained Release Formulation

The present work describes the physicochemical interaction of multi-walled carbon nanotubes (MWCNTs) with drugs differing in physicochemical properties and shows the potential of MWCNTs in extended release dosage form design. The drug-nanotube adsorbate of candesartan cilexetil (CC), diclofenac sodium (DS) and diltiazem hydrochloride (DH) was prepared by nanoprecipitation technique. Adsorbates were evaluated for drug content, drug release mechanism and physicochemical interaction using scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD) and dissolution study. The effect of carbon nanotube on the drug release profile was investigated. The prepared adsorbates exhibited satisfactory physico-chemical characteristics. The spectral studies shows only physical interaction between all drug molecules and MWCNTs. Hydrophobic drug shows stronger interaction with MWCNTs. Both the nanoscale diameter of MWCNTs and hydrophobicity of the drug affected the rate of release. The most hydrophobic drug candesartan cilexetil shows extended drug release of only 20% in 15 hours; highly water soluble drug diltiazem hydrochloride shows 90% release in 15 hours. MWCNTs thus promise considerable utility in the development of extended release drug delivery systems.

Etoposide encapsulation in surface‐modified poly(lactide‐co‐glycolide) nanoparticles strongly enhances glioma antitumor efficiency

Etoposide (VP-16) is a hydrophobic anticancer agent inhibiting Topoisomerase II, commonly used in pediatric brain chemotherapeutic schemes as mildly toxic. Unfortunately, despite its appropriate solubilization in vehicle solvents, its poor bioavailability and limited passage of the blood-brain barrier concur to disappointing results requiring the development of new delivery system forms. In this study, etoposide formulated as a parenteral injectable solution (Teva®) was loaded into all-biocompatible poly(lactide-co-glycolide) (PLGA) or PLGA/P188-blended nanoparticles (size 110-130 nm) using a fully biocompatible nanoprecipitation technique. The presence of coprecipitated P188 on encapsulation efficacies and in vitro drug release was investigated. Drug encapsulation was determined using HPLC. Inflammatory response was checked by FACS analysis on human monocytes. Cytotoxic activity of the various simple (Teva®) or double (Teva®-loaded NPs) formulations was studied on the murine C6 and F98 cell lines. Obtained results suggest that, although noninflammatory neither nontoxic by themselves, the use of PLGA and PLGA/P188 nanoencapsulations over pre-existing etoposide formulation could induce a greatly improved cytotoxic activity. This approach demonstrated a promising perspective for parenteral delivery of VP16 and potential development of a therapeutic entity.

Protein functionalized tramadol-loaded PLGA nanoparticles: preparation, optimization, stability and pharmacodynamic studies

Poly (d,l-lactide-co-glycolide acid) (PLGA) Nanoparticles (NPs) with sustained drug release and enhanced circulation time presents widely explored non-invasive approach for drug delivery to brain. However, blood-brain barrier (BBB) limits the drug delivery to brain. This can be overcome by anchoring endogenous ligand like Transferrin (Tf) and Lactoferrin (Lf) on the surface of NPs, allowing efficient brain delivery via receptor-mediated endocytosis. The aim of the present investigation was preparation, optimization, characterization and comparative evaluation of targeting efficiency of Tf- vs. Lf-conjugated NPs. Tramadol-loaded PLGA NPs were prepared by nanoprecipitation techniques and optimized using 33 factorial design. The effect of polymer concentration, stabilizer concentration and organic:aqueous phase ratio were evaluated on particle size (PS) and entrapment efficiency (EE). The formulation was optimized based on desirability for lower PS (<150 nm) and higher EE (>70%). Optimized PLGA NPs were conjugated with Tf and Lf, characterized and evaluated for stability study. Pharmacodynamic study was performed in rat after intravenous administration. The optimized formulation had 100 mg of PLGA, 1% polyvinyl alcohol (PVA) and 1:2 acetone:water ratio. The Lf and Tf conjugation to PLGA NPs was estimated to 186 Tf and 185 Lf molecules per NPs. Lyophilization was optimized at 1:2 ratio of NPs:trehalose. The NPs were found stable for 6 months at refrigerated condition. Pharmacodynamic study demonstrated enhanced efficacy of ligand-conjugated NPs against unconjugated NPs. Conjugated NPs demonstrated significantly higher pharmacological effect over a period of 24 h. Furthermore Lf functionalized NPs exhibited better antinociceptive effect as compared to Tf functionalized NPs.

Novel glycerol crosslinked poly(methyl methacrylate) synthesized by chemo-enzymatic method for controlled release application

Novel glycerol crosslinked poly(methyl methacrylate)(PMMA) was synthesized in one step in the presence of cocktail of chemical initiator and the biocatalyst Novozym 435 under mild reaction conditions. The objective of the study was to investigate the feasibility of glycerol to crosslink PMMA by biocatalytic route and to explore glycerol crosslinked PMMA as controlled release vehicle Effect of reaction time, temperature, glycerol to methylmethacrylate ratio, and methacrylate to toluene ratio was studied. Glycerol crosslinked PMMA swelled 289(±9)% in acetone and collapsed when immersed in water and in hexane. Swelling and shrinking of glycerol crosslinked PMMA was reversible in nature. Nanoparticles of glycerol crosslinked poly(methyl methacrylate) were synthesized by nanoprecipitation technique. The particles were spherical and of nanosize. The nanoparticles were used for the encapsulation and release of mosquito repellent N,N-diethyl-m-toluamide. Nanoparticles could encapsulate 8.5mg of repellant in 4h. The repellant got released from the nanoparticles at a controlled rate for a prolonged time interval. Release was more pronounced in deionized water and pH 7 buffer than in acetone. Addition of 1% NaCl further improved the release profile. 80% of encapsulated repellant was released from the nanoparticles in pH 7 buffer with 1% NaCl.

Enhancement of cellular uptake and cytotoxicity of curcumin-loaded PLGA nanoparticles by conjugation with anti-P-glycoprotein in drug resistance cancer cells

To compare the anti-cancer activity and cellular uptake of curcumin (Cur) delivered by targeted and non-targeted drug delivery systems in multidrug-resistant cervical cancer cells. Cur was entrapped into poly (DL-lactide-co-glycolide) (PLGA) nanoparticles (Cur-NPs) in the presence of modified-pluronic F127 stabilizer using nano-precipitation technique. On the surface of Cur-NPs, the carboxy-terminal of modified pluronic F127 was conjugated to the amino-terminal of anti-P-glycoprotein (P-gp) (Cur-NPs-APgp). The physical properties of the Cur-NPs, including particle size, zeta potential, particle morphology and Cur release kinetics, were investigated. Cellular uptake and specificity of the Cur-NPs and Cur-NPs-APgp were detected in cervical cancer cell lines KB-V1 (higher expression of P-gp) and KB-3-1 (lower expression of P-gp) using fluorescence microscope and flow cytometry, respectively. Cytotoxicity of the Cur-NPs and Cur-NPs-APgp was determined using MTT assay. The particle size of Cur-NPs and Cur-NPs-APgp was 127 and 132 nm, respectively. The entrapment efficiency and actual loading of Cur-NPs-APgp (60% and 5 μg Cur/mg NP) were lower than those of Cur-NPs (99% and 7 μg Cur/mg NP). The specific binding of Cur-NPs-APgp to KB-V1 cells was significantly higher than that to KB-3-1 cells. Cellular uptake of Cur-NPs-APgp into KB-V1 cells was higher, as compared to KB-3-1 cells. However, the cellular uptake of Cur-NPs and Cur-NPs-IgG did not differ between the two types of cells. Besides, the cytotoxicity of Cur-NPs-APgp in KB-V1 cells was higher than those of Cur and Cur-NPs. The results demonstrate that Cur-NPs-APgp targeted to P-gp on the cell surface membrane of KB-V1 cells, thus enhancing the cellular uptake and cytotoxicity of Cur.

Stabilized terbutaline submicron drug aerosol for deep lungs deposition: Drug assay, pulmonokinetics and biodistribution by UHPLC/ESI-q-TOF-MS method

Terbutaline submicron particles (SμTBS) were prepared by nanoprecipitation technique followed by spray drying for deep lungs deposition. Inhalable SμTBS particles were 645.16nm of diameter with 0.11μm of MMAD, suggested for better aerosol effects. Both submicron and micron-sized TBS particles were administered in rodents administered via major delivery routes, and their biological effects were compared by using UHPLC/ESI-q-TOF-MS method. TBS was found stable in all exposed conditions with 96.28–99.0% of recovery and <4.34% of accuracy (CV). An inhalation device was designed and validated to deliver medicines to lungs, which was found best at dose level of 25mg for 30min of fluidization. Both submicron and micron particles were compared for in vivo lung deposition and a 1.67 fold increase in concentration was observed for SμTBS exposed by inhalation. Optimized DPI formulation contained lesser fraction of ultrafine particle (<500nm) with the major fraction of submicron particles (>500nm), advocated for better targeting to lungs. UHPLC/ESI-q-TOF-MS confirmed that designed submicron particles has been successfully delivered to the lungs. From tongue to lungs, the landing of pulmonary medicines can be improved by submicronization technology.

PLGA nanoparticles loaded with etoposide and quercetin dihydrate individually: in vitro cell line study to ensure advantage of combination therapy.

PLGA nanoparticles, separately loaded with etoposide (ETN) and quercetin dihydrate (QDN), were prepared by adapting the solvent diffusion (nanoprecipitation) technique. The effect of formulation variables such as amount of polymer, theoretical drug loading, surfactant concentration, and aqueous and organic phase volumes on particle size and entrapment efficiency, were systematically studied. The optimal formulations obtained were of submicron size (153.4 ± 4.2 nm for ETN and 148.6 ± 1.6 nm for QDN) and with low polydispersity indices (0.058 ± 0.02 for ETN and 0.088 ± 0.03 for QDN). The entrapment efficiencies were found as 63.88 ± 1.5 % and 41.36 ± 3.4 % for ETN and QDN, respectively. The characterization of ETN and QDN was done by measuring the zeta potential, TEM, and DSC analysis. The comparison was made in respect of in vitro cytotoxicity assay using cancer cell line A549 (human lung adenocarcinoma epithelial cell line). The results revealed significant increase in cytotoxicity in nanoparticle formulations than their respective free drug. The comparison was also made with respect to cytotoxic activity of individual drug and combination of drugs in the form of free drugs as well as nanoparticles. The combination treatment in the form of nanoparticles is found to produce best results among the treatments used in cytotoxicity studies.

Characteristics and Antioxidant Activities of Silymarin Nanoparticles

Silymarin, a well known hepatoprotective drug, has been routinely used in treating liver disorders. However, its bioavailability and therapeutic efficiency are limited by the poor aqueous solubility. In this study, we used the nanoprecipitation technique to develop a nanoparticles system to improve the solubility of silymarin. The newly developed silymarin nanoparticles were characterized for mean particle size, morphology, intermolecular interaction, crystalline features and dissolution property, as well as assessing for antioxidant activities. Results indicated that a drastic change in the physiochemical properties of silymarin was noted in the form of nanoparticles, as displayed by the extremely small particle size (46.1 +/- 1.73 nm), the formation of intermolecular hydrogen bonding between silymarin and matrix of nanoparticles, and the rendering of amorphous state. These phenomena have contributed to the enhanced dissolution property of silymarin nanoparticles, as well as a greater potency in DPPH radical scavenging, anti-superoxide anion formation, and superoxide anion scavenging activities than the crude silymarin. The present study concludes that silymarin nanoparticles have an improved physicochemical property as demonstrated by an increased solubility and enhanced antioxidant activities.

Investigation on design of stable etoposide-loaded PEG-PCL micelles: effect of molecular weight of PEG-PCL diblock copolymer on the in vitro and in vivo performance of micelles

In the present study, six different molecular weight diblock copolymer of methoxy poly (ethylene glycol)-b-poly (ϵ-caprolactone) (MPEG-PCL) were synthesized and characterized and was used for fabrication of etoposide-loaded micelles by nanoprecipitation technique. The particle size and percentage drug entrapment of prepared micelles were found to be dependent on the molecular weight of PCL block and drug to polymer ratio. The maximum drug loading of 5.32% was found in micellar formulation MPEG5000-PCL10000, while MPEG2000-PCL2000 exhibited 2.73% of maximum drug loading. A variation in the fixed aqueous layer thickness and PEG surface density of micellar formulations was attributed to difference in MPEG molecular weight and interaction of PEG and PCL block of copolymer. The MPEG2000-PCL2000 micelles demonstrated poor in vitro stability among other micellar formulations, due to its interaction with bovine serum albumin and immediate release of drug from micelles. Furthermore, plain etoposide and MPEG2000-PCL2000 micelles exhibited greater extent of hemolysis, due to presence of surfactants and faster release of drug from micelles, respectively. The biodistribution studies carried out on Ehrlich ascites tumor-bearing Balb/C mice confirmed higher accumulation of etoposide-loaded micellar formulation at tumor site compared to plain etoposide due to enhanced permeability and retention effect.

Enzymatically degradable nanoparticles of dextran esters as potential drug delivery systems

Abstract Dextran decanoate esters with degrees of substitution (average molar ratio of ester functions to glucose repeat units) between 20 and 150% were used to form nanoparticles via nanoprecipitation technique. Particle size and colloidal stability of nanoparticles were found to depend on dextran concentration and degree of substitution. The colloidal stability of nanoparticle suspensions in sodium chloride solutions was improved by using a water-soluble dextran derivative as stabilizer. Enzymatic hydrolysis of ester bonds by porcine pancreatic lipase was demonstrated for highly modified dextran derivatives (up to DS = 150%). Complete degradation of low modified dextrans (DS up to 25%) by dextranase occurred within 7 days. Finally, encapsulation of lidocaine (as a model drug) into nanoparticles obtained with dextran esters (DS ranging between 21 and 150%) was investigated.

Poly(ether-ester anhydride)-based amphiphilic block copolymer nanoparticle as delivery devices for paclitaxel

This Letter focuses on the preparation and characterisation of a novel amphiphilic multiblock poly(ether-ester anhydride) copolymer [poly(sebacic acid-b-poly(ethylene glycol)-b-sebacic acid) (PES)], paclitaxel-loaded PES nanoparticles (NPs), in vitro evaluation of the release of paclitaxel and cytotoxicity of NPs. PES was prepared by melt polycondensation and the PES NPs were prepared by nanoprecipitation technique. In vitro release behaviour of the paclitaxel-loaded NPs was investigated by high-performance liquid chromatography (HPLC). In vitro cytotoxicity of NPs was evaluated by MTT assay. The composition and structure of PES are consistent with that of the designed copolymer. The paclitaxel-loaded NPs are of spherical shape and size lower than 200 nm. Paclitaxel can be continuously released from the paclitaxel-loaded NPs. The PES NPs are non-toxic to cells. The results suggest that PES NPs are a potential candidate nanocarrier material for the controlled delivery of paclitaxel and other hydrophobic compounds.

Drug delivery by polymeric nanoparticles induces autophagy in macrophages

Drug delivery nanosystems are currently used in human therapy. In preliminary studies we have observed that Eudragit ® RS nanoparticles, prepared by nanoprecipitation or double emulsion techniques, are cytotoxic for NR8383 rat macrophages. In this study, we expand our previous analysis and suggest that unloaded Eudragit ® RS nanoparticles prepared by nanoprecipitation (NP/ERS) may induce important morphological and biochemical cellular modifications leading to cellular death. In NR8383 rat macrophages cell line exposed to doses varying from 15 to 100 μg/mL, NP/ERS nanoparticles are internalized inside the cells, reach the mitochondria and alter the structure of these organelles. In addition, the exposure to nanoparticles induces cellular autophagy as demonstrated by electron microscopy analysis, microchip array, qRT-PCR and Western blot assays. Although toxicity of nanoparticles has already been evidenced, it is the first time that results show clearly that the toxicity of polymeric nanovectors may be related to an activation of autophagy.

Synthesis and characterization of surface‐modified PBLG nanoparticles for bone targeting: In vitro and in vivo evaluations

In this study, poly(γ-benzyl-l-glutamate) (PBLG) polypeptide derivatives were synthesized by ring-opening polymerization of amino acid N-carboxyanhydride using selected amine-terminated initiators. Alendronate, a targeting moiety that has a strong affinity for bone, was conjugated to PBLG. Monomethoxy polyethylene glycol (PEG) was used for a hydrophilic layer on the surface of the nanoparticles (NPs) to avoid reticuloendothelial system uptake. NPs were prepared by nanoprecipitation technique not only for PBLG or PBLG-PEG but also for composite polymers with different ratios. Fluorescein isothiocyanate would be attached to the NPs as a labeling agent. The size and morphology of NPs were evaluated by dynamic laser light scattering and transmission electron microscopy, and were found to be in a useful range (less than 80 nm) for bone-targeted drug delivery. In addition, the PEGylation of NPs was supported by isothermal titration calorimetry analysis. The bone-targeting potential of NPs was evaluated in vitro by calcium binding and hydroxyapatite affinity assays, and in vivo by fluorescent imaging experiments on rats. The targeted NPs showed bright fluorescent labeling in femur tissue. These results demonstrated the possibility of optimized NPs prepared with new PBLG derivatives to accumulate in bone successfully.

Enhanced anticancer activity of naringenin-loaded nanoparticles in human cervical (HeLa) cancer cells

Naringenin (NAR) is a naturally occurring plant bioflavonoid present in citrus fruits and possesses a wide range of biological application including anticancer effects. However, its prominent application in cancer is limited due to its suboptimal pharmacokinetics and poor bioavailability at the tumor sites. The aim of the present study was to develop naringenin-loaded nanoparticles (NARNPs) and to evaluate the anticancer potency of the prepared NARNPs in human cervical (HeLa) cancer cells. NARNPs were prepared by nanoprecipitation technique and characterized by dynamic light scattering (DLS), transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimeter (DSC), and X-ray diffraction (XRD). The in vitro drug release by UV spectroscopy showed there was a sustained drug delivery pattern of NARNPs. MTT-based colorimetric assay revealed higher cytotoxic efficacy of NARNPs than free NAR in HeLa cells. Further, NARNPs treatment significantly ( P < 0.05) increased intracellular ROS levels, lipid peroxidation status (TBARS) and decreased GSH levels when compared to free NAR treatment in HeLa cells. It has been also noticed that there was a significant alteration of mitochondrial membrane potential and the presence of apoptotic indices (membrane blebbing, nuclear fragmentation) in NARNPs treated cancer cells. Taken together, the present study demonstrates the anticancer potential of prepared NARNPs than free NAR in cervical cancer cells in vitro.

AmbiOnp: Solid Lipid Nanoparticles of Amphotericin B for Oral Administration

Amphotericin B is the most effective gold standard drug against various fungal infections, especially in second line treatment of leishmaniasis. However, its usefulness is limited due to severe nephrotoxicity, which may lead to kidney failure. Due to its poor oral bioavailability, it is often administered parenterally to patients suffering from systemic fungal infection or visceral leishmaniasis (kala azar). In this investigation, solid lipid nanoparticles were formulated for oral administration of Amphotericin B. For this purpose, novel microemulsion based nanoprecipitation technique was employed. The influence of process variables such as sonication and dialysis time was studied. The optimized formulation was characterized for parameters such as particle size, polydispersity index, zeta potential, drug content and entrapment efficiency. The pH stability of the developed Amphotericin B solid lipid nanoparticles (AmbiOnp) at pH 1.2, 4, 6.8 values demonstrated enhanced protection of entrapped Amphotericin B. Further, single dose acute toxicity study established the safety of AmbiOnp for oral administration. In vivo pharmacokinetic studies revealed increase in % relative bioavailability of AmbiOnp in comparison to the plain drug. Additionally, the t1/2 of encapsulated Amphotericin B was significantly greater than that of plain drug, indicating the controlled release of Amphotericin B from AmbiOnp. Overall, the developed formulation; AmbiOnp was found to be successful in oral delivery of Amphotericin B.

Synthesis of fluorescent methoxy poly(ethylene glycol)‐b‐Poly(ethyl cyanoacrylate)–2‐(N‐carbazolyl) ethyl methacrylate copolymer via living oxyanion‐initiated polymerization

AbstractThe fluorescent amphiphilic block copolymer methoxy poly(ethylene glycol) (mPEG)‐b‐poly(ethyl cyanoacrylate) (PECA)–2‐(N‐carbazolyl) ethyl methacrylate (CzEMA) was synthesized via living oxyanion‐initiated polymerization. mPEG‐b‐PECA–CzEMA was characterized by gel permeation chromatography, 1H‐NMR, and Fourier transform infrared spectroscopy. The results indicate that the polymerization was well controlled with a narrow molecular weight distribution. The mPEG‐b‐PECA–CzEMA nanoparticles prepared by nanoprecipitation techniques showed a narrow size distribution with an average diameter of less than 100 nm. The mPEG‐b‐PECA–CzEMA exhibited a strong carbazole fluorescence. Furthermore, it was found that the fluorescence intensity of mPEG‐b‐PECA–CzEMA was sensitive to a change in solvent. The results indicate that a subtle change in the state of the polymer micellar association may have altered the state of carbazole groups, which was responsible for the fluorescence emission. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012