Swati Gupta

Publications of Swati Gupta

• Development and evaluation of tripalmitin emulsomes for the treatment of experimental visceral leishmaniasis.

  Authors: Ajay Pal, Swati Gupta, Anil Jaiswal, Anuradha Dube, Suresh P Vyas

  Journal of liposome research. 07/2011; 22(1):62-71.

  The antifungal and antileishmanial agent amphotericin B (AmB) was formulated in tripalmitin based nanosize lipid partices (emulsomes) for macrophage targeting for the treatment of visceralThe antifungal and antileishmanial agent amphotericin B (AmB) was formulated in tripalmitin based nanosize lipid partices (emulsomes) for macrophage targeting for the treatment of visceral leishmaniasis (VL). Emulsomes were modified by coating them with macrophage-specific ligand (O-palmitoyl mannan, OPM). The antileishmanial activity of AmB (0.5 and 1 mg/kg) was investigated in-vivo against VL by the inhibition of parasitic load in the spleen of L. donovani infected hamsters after intraperitoneal injections of AmB-Doc (Mycol), plain emulsomes (TPEs) and OPM coated emulsomes (TPEs-OPM). The formulations were found to be less effective at the dose of 0.5 mg/kg. At the dose of 1 mg/kg, formulation TPEs-OPM eliminated intracellular amastigotes of L. donovani within splenic macrophages more efficiently (62.76 ± 3.54 % parasite inhibition) than the formulation TPEs (42.68 ± 2.36 % parasite inhibition) (P < 0.01) or AmB-Doc (25.87 ± 3.87 % parasite inhibition) (P < 0.001). Our results suggest that these formulations (plain and ligand grafted emulsomes) are a promising substitute to the conventional AmB-Doc formulation for the treatment of VL.

• EGFR targeted PLGA nanoparticles using gemcitabine for treatment of pancreatic cancer.

  Authors: Sahil Aggarwal, Sachin Yadav, Swati Gupta

  Journal of biomedical nanotechnology. 02/2011; 7(1):137-8.

  The present study aimed to prepare and characterize anti EGFR monoclonal antibody (mab) conjugated Gemcitabine loaded PLGA nanoparticles for their selective delivery to pancreatic cells andThe present study aimed to prepare and characterize anti EGFR monoclonal antibody (mab) conjugated Gemcitabine loaded PLGA nanoparticles for their selective delivery to pancreatic cells and evaluation of the systems in vitro. It was observed that direct covalent coupling of antibodies to glutaraldehyde activated nanoparticles is an appropriate method to achieve cell-type specific drug carrier systems based on polymeric nanoparticles that have potential to be applied for targeted chemotherapy in EGFR positive cancer.

• Development and characterization of doxorubicin loaded microparticles against experimental visceral leishmaniasis.

  Authors: Sheeshpal Sharma, Pankaj Kumar, Anil Jaiswal, Anuradha Dube, Swati Gupta

  Journal of biomedical nanotechnology. 02/2011; 7(1):135-6.

  Visceral leishmaniasis (VL) is the most severe of all the forms of leishmaniasis and usually lethal if untreated. The present work aimed to develop and characterize doxorubicin loaded mannanVisceral leishmaniasis (VL) is the most severe of all the forms of leishmaniasis and usually lethal if untreated. The present work aimed to develop and characterize doxorubicin loaded mannan conjugated microparticles against experimental visceral leishmaniasis for selective and targeted delivery of doxorubicin to the macrophages of liver and spleen for the effective chemotherapy of VL. Macrophage targeting using doxorubicin loaded PLGA-microparticles would certainly improve the chemotherapy with reduced side effects against VL.

• Possible role of epidermal growth factor receptors in the therapy of pancreatic cancer.

  Authors: Sahil Aggarwal, Swati Gupta, Manish K Gupta, R S R Murthy, Suresh P Vyas

  Critical reviews in therapeutic drug carrier systems. 01/2011; 28(4):293-356.

  Pancreatic cancer is considered an 'orphan' cancer because of its relative low incidence. Unfortunately, even with early diagnosis, mortality rates are high and it ranks eighth in the worldwidePancreatic cancer is considered an 'orphan' cancer because of its relative low incidence. Unfortunately, even with early diagnosis, mortality rates are high and it ranks eighth in the worldwide ranking of deaths due to cancer. The administration of chemotherapeutic agents for the treatment of advanced disease has failed, and current research focuses on the understanding of molecular pathways in order to investigate the role of targeted therapy. It has been known that the development and the progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes, and the deregulation of many signaling pathways of various growth factors, among which the epidermal growth factor receptor (EGFR) plays an important role. Growth factor receptors and their ligands not only regulate normal cell processes, but have also been identified as key regulators of human cancer formation. EGFR has been found to be expressed and altered in pancreatic cancer and clearly plays a significant role in tumor development and progression, including cell proliferation, regulation of apoptotic cell death, angiogenesis, and metastatic spread. The amplitude and kinetics of growth factor signaling are determined mainly by a highly regulated endocytic process that sorts and directs activated receptors to degradation in lysosomes. Therefore, EGFR is a legitimate therapeutic target. The aim of this review is to outline the endocytic escape of EGFRs in cancer with special attention towards recent advances in various approaches adopted for EGFR targeting.

• Chitosan-based macrophage-mediated drug targeting for the treatment of experimental visceral leishmaniasis.

  Authors: Sijumon Kunjachan, Swati Gupta, Anil K Dwivedi, Anuradha Dube, Manish K Chourasia

  Journal of microencapsulation. 01/2011; 28(4):301-10.

  The potential of chitosan microparticles as a carrier of doxorubicin for the treatment of visceral leishmaniasis was evaluated by macrophage-mediated drug targeting approach. Cationic charge ofThe potential of chitosan microparticles as a carrier of doxorubicin for the treatment of visceral leishmaniasis was evaluated by macrophage-mediated drug targeting approach. Cationic charge of doxorubicin was masked by complexing it with dextran sulphate (a poly anion) in order to facilitate its incorporation into cationic chitosan microparticles. Prior to in vitro and in vivo studies, characterization studies were carried out systematically: particle size (∼1.049 µm), surface morphology (fluorescence microscopy - spherical structured microparticles), Fourier transform infrared spectroscopy (to characterize effective cross-linking) and differential scanning calorimetry. In vitro studies were carried out in J774.1 in order to check the effective endocytotic uptake of microparticles by macrophages. In vivo studies were conducted in Syrian golden hamsters as per well-established protocols and the results drawn from in vivo studies displayed substantial reduction in leishmanial parasite load for doxorubicin-encapsulated chitosan microparticles: ∼78.2 ± 10.4%, when compared to the control (free doxorubicin): 33.3 ± 2.4%.

• Design, synthesis and docking studies on phenoxy-3-piperazin-1-yl-propan-2-ol derivatives as protein tyrosine phosphatase 1B inhibitors.

  Authors: Swati Gupta, Gyanendra Pandey, Neha Rahuja, Arvind K Srivastava, Anil K Saxena

  Bioorganic & medicinal chemistry letters. 10/2010; 20(19):5732-4.

  A series of substituted phenoxy-3-piperazin-1-yl-propan-2-ols has been synthesized and evaluated for PTP1B inhibitory activity in vitro and for antidiabetic activity in vivo. Two molecules viz. 4aA series of substituted phenoxy-3-piperazin-1-yl-propan-2-ols has been synthesized and evaluated for PTP1B inhibitory activity in vitro and for antidiabetic activity in vivo. Two molecules viz. 4a and 5b showed PTP1B inhibition of 31.58% and 35.90% at 100 μM concentration. The compound 4a also showed 40.3% normalization of plasma glucose levels at 100mg/kg in Sugar-loaded model (SLM) and 32% activity in Streptozodocin model (STZ). The docking studies of these molecules revealed that hydrogen bond formation with Arg221 is important for activity.

• Drug delivery strategies for therapy of visceral leishmaniasis.

  Authors: Swati Gupta, Ajay Pal, Suresh P Vyas

  Expert opinion on drug delivery. 03/2010; 7(3):371-402.

  Visceral leishmaniasis (VL) is the most overwhelming type of leishmaniasis associated with the poverty of developing countries and usually mortal if untreated. Most of the conventionally used dosageVisceral leishmaniasis (VL) is the most overwhelming type of leishmaniasis associated with the poverty of developing countries and usually mortal if untreated. Most of the conventionally used dosage forms offer us the shortcomings of toxic side effects and emergence of drug resistance. Several efforts have been made to overcome the barriers involved in the treatment of VL. Colloidal carriers extensively represent the drug delivery systems (DDSs) for intracellular localization of antileishmanial compounds in macrophage-rich organs such as liver, spleen and bone marrow. These DDSs offer superior therapeutic efficacy over the conventional treatment in terms of site-specific drug delivery with reduced side effects. However, after 35 years of research in the field, AmBisome (Amphotericin B liposome for injection, Astellas Pharma US, Inc.) is the only DDS used against the VL. A literature search was performed (for drugs and DDSs against VL) on PubMed and through Google. This review aims to describe the pathophysiology of VL and its current conventional treatment with special reference to DDSs designed against VL. On reviewing the conventional drugs and DDSs developed against VL, it is concluded that advances in the field of targeted drug delivery can result in more efficient strategies for the therapy of VL.

• Emerging role of vesicular carriers for therapy of visceral leishmaniasis: conventional versus novel.

  Authors: Navneet Kumar, Swati Gupta, Anuradha Dube, Suresh P Vyas

  Critical reviews in therapeutic drug carrier systems. 01/2010; 27(6):461-507.

  Visceral leishmaniasis (VL) is a systemic protozoan infection that infects a million people living in subtropical and tropical areas. Drugs are the major treatment available against this fatalVisceral leishmaniasis (VL) is a systemic protozoan infection that infects a million people living in subtropical and tropical areas. Drugs are the major treatment available against this fatal infection. Conventional chemotherapy of VL involves treatment with pen- tavalent antimonials, pentamidine, paromomycin, miltefosine, etc., but this treatment is challenging because of the failure of drugs to penetrate macrophages where the parasite hides, toxic side effects, and drug resistance due to incomplete treatment schedules. The newer therapeutic approach of combination therapy employing multi-drug combinations provides improved treatment of VL because the combination reduces length of treatment, relapse, and risk of toxicity and increases the therapeutic index. Although considerable success has been attained using combination therapies, none has yet achieved commercial status. Therefore, there is an urgent need of designing novel, site-specific leishmanicidal drug carriers for safe and effective management of VL. Colloidal carriers such as liposomes, niosomes, emulsomes, and their engineered versions offer superior therapeutic efficacy over the conventional treatment in terms of site-specific drug delivery related to absolute treatment of disease with reduced side effects and toxicity. The control over spatial and sequential distribution of drug molecules after systemic or localized administration represents the major dispute in drug-delivery systems, and this can be resolved by the use of these colloidal carriers. The present review describes current conventional and combination drug therapies with special consideration given to the emerging role of novel vesicular colloidal carriers designed against VL. Colloidal carriers employing drugs in combination could lead to reductions in the duration of conventional treatment, better patient compliance, and the prevention of anti-leishmanial drug resistance or toxicity.

• Carbopol/chitosan based pH triggered in situ gelling system for ocular delivery of timolol maleate.

  Authors: Swati Gupta, Suresh P Vyas

  Scientia pharmaceutica. 01/2010; 78(4):959-76.

  The poor bioavailability and therapeutic response exhibited by conventional ophthalmic preparations due to rapid precorneal elimination, dilution and nasolacrimal drainage of the drug may beThe poor bioavailability and therapeutic response exhibited by conventional ophthalmic preparations due to rapid precorneal elimination, dilution and nasolacrimal drainage of the drug may be vanquished by the use of in situ gelling systems that are instilled as drops in to the eye and undergo a sol-gel transition in the cul-de-sac. Timolol eye drops may cause systemic side effects in glaucoma patients due to absorption of the drug into systemic circulation. In situ gelling system of this drug can provide localized effect with reduced contraindications, improved patient compliance and better therapeutic index. The present work describes the formulation and evaluation of an ophthalmic delivery system of an antiglaucoma drug, timolol maleate (TM) based on the concept of pH-triggered in situ gelation. Polyacrylic acid (carbopol) was used as the gelling agent in combination with chitosan (amine polysaccharide), which was acted as a viscosity-enhancing agent. Formulations were evaluated for pH, viscosity, gelling capacity and drug content. The 0.4% w/v carbopol/0.5% w/v chitosan based in situ gelling system was in liquid state at room temperature and at the pH formulated (pH 6.0) and underwent rapid transition into the viscous gel phase at the pH of the tear fluid (lacrimal fluid) (pH 7.4). The in vitro drug release and in vivo effects of the developed in situ gelling system were compared with that of Glucomol (a 0.25% TM ophthalmic solution), 0.4% w/v carbopol solution as well as liposomal formulation. The results clearly demonstrated that developed carbopol-chitosan based formulation was therapeutically efficacious and showed a fickian (diffusion controlled) type of release behaviour over 24 h periods. The developed system is thus a viable alternative to conventional eye drops and can also prevent the rapid drainage as in case of liposomes.

• An orally effective dihydropyrimidone (DHPM) analogue induces apoptosis-like cell death in clinical isolates of Leishmania donovani overexpressing pteridine reductase 1.

  Authors: Neeloo Singh, Jaspreet Kaur, Pranav Kumar, Swati Gupta, Nasib Singh, Angana Ghosal, Avijit Dutta, Ashutosh Kumar, RamaPati Tripathi, Mohammad Siddiqi, Chitra Mandal, Anuradha Dube

  Parasitology research. 08/2009;

  The protozoan parasite Leishmania donovani is the causative agent of visceral leishmaniasis. The enzyme pteridine reductase 1 (PTR1) of L. donovani acts as a metabolic bypass for drugs targetingThe protozoan parasite Leishmania donovani is the causative agent of visceral leishmaniasis. The enzyme pteridine reductase 1 (PTR1) of L. donovani acts as a metabolic bypass for drugs targeting dihydrofolate reductase (DHFR); therefore, for successful antifolate chemotherapy to be developed against Leishmania, it must target both enzyme activities. Leishmania cells overexpressing PTR1 tagged at the N-terminal with green fluorescent protein were established to screen for proprietary dihydropyrimidone (DHPM) derivatives of DHFR specificity synthesised in our laboratory. A cell-permeable molecule with impressive antileishmanial in vitro and in vivo oral activity was identified. Structure activity relationship based on homology model drawn on our recombinant enzyme established the highly selective inhibition of the enzyme by this analogue. It was seen that the leishmanicidal effect of this analogue is triggered by programmed cell death mediated by the loss of plasma membrane integrity as detected by binding of annexin V and propidium iodide (PI), loss of mitochondrial membrane potential culminating in cell cycle arrest at the sub-G0/G1 phase and oligonucleosomal DNA fragmentation. Hence, this DHPM analogue [(4-fluoro-phenyl)-6-methyl-2-thioxo-1, 2, 3, 4-tetrahydropyrimidine-5-carboxylic acid ethyl ester] is a potent antileishmanial agent that merits further pharmacological investigation.

• A pro-apoptotic effect of Landrace of Piper betle- Bangla Mahoma on Leishmania donovani may be due to high content of eugenol.

  Authors: Pragya Misra, Awanish Kumar, Prashant Khare, Swati Gupta, Nikhil Kumar, Anuradha Dube

  Journal of medical microbiology. 07/2009;

  In the absence of effective and safe treatment of Kala-azar (VL) - a most devastating parasitic disease caused by Leishmania donovani a need for the search of antileishmanial from natural resources,In the absence of effective and safe treatment of Kala-azar (VL) - a most devastating parasitic disease caused by Leishmania donovani a need for the search of antileishmanial from natural resources, in common use, is imperative. Recently, a comparative in vitro antileishmanial activity of methanolic extract of two landraces of Piper betle- Bangla Mahoba (PB-BMM) and Kapoori Vellaikodi (PB-KVM) has been reported. Herein, the putative pathway responsible for death induced by the effective extract of PB-BMM in promastigotes as well as intracellular amastigotes form of L. donovani was assessed using various biochemical approaches. It was observed that PB-BM is capable of selectively inhibiting both the stages of Leishmania parasites by accelerating apoptotic events by generation of ROS targeting mitochondrion without any cytotoxicity to macrophages. Study was extended to reason out the presence/absence of activity in PB-BMM and PB-KVM on the basis of differences in essential oil composition present in methanolic extract assessed by gas chromatography and mass spectra. The essential oil from PB-BM was found to be rich in eugenol as compared to PB-KV. The antileishmanial efficacy of PB-BMM mediated through apoptosis is probably due to the higher content of eugenol in active landrace. This observation emphasizes the need of extending the studies related to traditional medicines from bioactive plants below species to gender/landrace level for better efficacy and reproducibility.

• Synthesis of protein tyrosine phosphatase 1B inhibitors: model validation and docking studies.

  Authors: Anil K Saxena, Gyanendra Pandey, Swati Gupta, Amar Bahadur Singh, Arvind K Srivastava

  Bioorganic & medicinal chemistry letters. 05/2009; 19(8):2320-3.

  The designed and synthesized 2-(4-methoxyphenyl) ethyl] acetamide derivatives (3a, 3b and 3c) were evaluated for their PTP1B inhibitory activity where they showed IC(50) values 69 microM, 87 microMThe designed and synthesized 2-(4-methoxyphenyl) ethyl] acetamide derivatives (3a, 3b and 3c) were evaluated for their PTP1B inhibitory activity where they showed IC(50) values 69 microM, 87 microM and 71 microM, respectively. These results correlated well with the docking studies and in vivo screening of the compounds for their antidiabetic activity in SLM and STZ models.

• Peganine hydrochloride dihydrate an orally active antileishmanial agent.

  Authors: Tanvir Khaliq, Pragya Misra, Swati Gupta, K Papi Reddy, Ruchir Kant, P R Maulik, Anuradha Dube, T Narender

  Bioorganic & medicinal chemistry letters. 04/2009;

  Protozoic infections caused by genus Leishmania pose an enormous public health threat in developing countries, compounded by the toxicity and resistance to current therapies. Under the aegis of ourProtozoic infections caused by genus Leishmania pose an enormous public health threat in developing countries, compounded by the toxicity and resistance to current therapies. Under the aegis of our ongoing program on drug discovery and development on antileishmanial agents from plants, we carried out bioassay guided fractionation on Peganum harmala seeds which resulted in the isolation of 1 as an antileishmanial agent. 2D-NMR spectral data and single crystal X-ray crystallography data indicated 1 as peganine hydrochloride in dihydrated form. The compound 1 exhibited in-vitro activity against both extracellular promastigotes as well as intracellular amastigotes residing within murine macrophages in Leishmania donovani. Furthermore, 1 also exhibited in-vivo activity, 79.6 (+/-8.07)% against established VL in hamsters at a dose of 100mg/kgb.wt.

• Antileishmanial activity in vitro and in vivo of constituents of sea cucumber Actinopyga lecanora.

  Authors: Nasib Singh, Rajesh Kumar, Swati Gupta, Anuradha Dube, V Lakshmi

  Parasitology research. 08/2008; 103(2):351-4.

  In the search of new antileishmanial drugs from marine resources, we have investigated Actinopyga lecanora, a coral reef sea cucumber, for its in vitro and in vivo activities. Methanol extract andIn the search of new antileishmanial drugs from marine resources, we have investigated Actinopyga lecanora, a coral reef sea cucumber, for its in vitro and in vivo activities. Methanol extract and n-butanol fraction of A. lecanora exhibited excellent Leishmania donovani inhibition. Among the two glycosides isolated from n-butanol fraction, holothurin B (2) displayed excellent in vitro and moderate in vivo leishmanicidal activity, whereas holothurin A (1) revealed only moderate action. These findings provide an important marine lead toward the development of new antileishmanial drugs and necessitate the further exploration of rich and diverse marine resources for more potent bioactive molecules.

• Antileishmanial efficacy of amphotericin B bearing emulsomes against experimental visceral leishmaniasis.

  Authors: Swati Gupta, Anuradha Dube, Suresh P Vyas

  Journal of drug targeting. 08/2007; 15(6):437-44.

  Amphotericin B (AmB) was formulated in trilaurin-based emulsomes (nanosize lipid particles) stabilized by soya phosphatidylcholine (PC), as a new delivery system for macrophage targeting for theAmphotericin B (AmB) was formulated in trilaurin-based emulsomes (nanosize lipid particles) stabilized by soya phosphatidylcholine (PC), as a new delivery system for macrophage targeting for the treatment of visceral leishmaniasis (VL). Emulsomes were modified by coating them with macrophage-specific ligand (O-palmitoyl mannan, OPM). The antileishmanial activity of AmB-deoxycholate (AmB-Doc) and emulsome entrapped AmB was tested in vitro in Leishmania donovani infected macrophage-amastigote system (J774A.1 cells), which showed higher efficacy of OPM grafted AmB emulsomes (TLEs-OPM) over plain AmB emulsomes (TLEs) and AmB-Doc. The in vivo antileishmanial activity of the AmB (0.5 mg/kg) was tested in AmB-Doc, TLEs and TLEs-OPM forms against VL in L. donovani infected hamsters. Formulation TLEs-OPM eliminated intracellular amastigotes of L. donovani within splenic macrophages more efficiently (73.7 +/- 6.7% parasite inhibition) than the formulation TLEs (51.7 +/- 5.4% parasite inhibition) (P < 0.01) or AmB-Doc (30.4 +/- 4.8% parasite inhibition) (P < 0.001). Our results suggest that these newer formulations (plain and ligand appended emulsomes) are a promising alternative to the conventional AmB-Doc formulation for the treatment of VL.

• Development and characterization of amphotericin B bearing emulsomes for passive and active macrophage targeting.

  Authors: Swati Gupta, Suresh P Vyas

  Journal of drug targeting. 05/2007; 15(3):206-17.

  The antifungal and antileishmanial agent amphotericin B (AmB) has been complexed with lipids to develop a less toxic formulation of AmB. Because lipid particles are phagocytized by theThe antifungal and antileishmanial agent amphotericin B (AmB) has been complexed with lipids to develop a less toxic formulation of AmB. Because lipid particles are phagocytized by the reticuloendothelial system, lipid associated AmB should be concentrated in infected macrophages of liver and spleen and be very effective against visceral leishmaniasis (VL) and systemic fungal infections. Therefore, AmB was formulated in trilaurin based nanosize lipid particles (emulsomes) stabilized by soya phosphatidylcholine (PC) as a new intravenous drug delivery system for macrophage targeting. Emulsomes were prepared by cast film technique followed by sonication to obtain particles of nanometric size range. Formulations were optimized for AmB to lipid ratio, sonication time and PC to trilaurin ratio. Emulsomes were modified by coating them with macrophage-specific ligand (O-palmitoyl mannan, OPM). The surface modified emulsomes and their plain counterparts were characterised for size, shape, lamellarity and entrapment efficiency. Fluorescence microscopy study showed significant localization of plain and coated emulsomes inside the liver and spleen cells of golden hamsters. In vivo organ distribution studies in albino rats demonstrated that extent of accumulation of emulsome entrapped AmB in macrophage rich organs, particularly liver, spleen and lungs was significantly high when compared against the free drug (AmB-deoxycholate or AmB-Doc). The rate and extent of accumulation were found to increase further on ligand anchoring. Further, a significantly higher (P < 0.05) drug concentration in the liver was estimated over a period of 24 h for OPM coated emulsomes than for plain emulsomes. We concluded that OPM coated emulsomes could fuse with the macrophages of liver and spleen due to ligand-receptor interaction and could target the bioactives inside them. The proposed plain and OPM coated emulsome based systems showed excellent potential for passive and active intramacrophage targeting, respectively and the approach could be a successful alternative to the currently available drug regimens of VL and systemic fungal infections.

• Optimizing efficacy of amphotericin B through nanomodification.

  Authors: Suresh P Vyas, Swati Gupta

  International journal of nanomedicine. 02/2006; 1(4):417-32.

  Fungal infections and leishmaniasis are an important cause of morbidity and mortality in immunocompromised patients. The macrolide polyene antibiotic amphotericin B (AmB) has long been recognized asFungal infections and leishmaniasis are an important cause of morbidity and mortality in immunocompromised patients. The macrolide polyene antibiotic amphotericin B (AmB) has long been recognized as a powerful fungicidal and leishmanicidal drug. A conventional intravenous dosage form of AmB, AmB- deoxycholate (Fungizone or D-AmB), is the most effective clinically available for treating fungal and parasitic (leishmaniasis) infections. However, the clinical efficacy of AmB is limited by its adverse effects mainly nephrotoxicity. Efforts to lower the toxicity are based on synthesis of AmB analogues such as AmB esters or preparation of AmB-lipid associations in the forms of liposomal AmB (L-AmB or AmBisome), AmB lipid complex (Abelcet or ABLC), AmB colloidal dispersion (Amphocil or ABCD), and intralipid AmB. These newer formulations are substantially more expensive, but allow patients to receive higher doses for longer periods of time with decreased renal toxicity than conventional AmB. Modifications of liposomal surface in order to avoid RES uptake, thus increased targetability has been attempted. Emulsomes and other nanoparticles are special carrier systems for intracellular localization in macrophage rich organs like liver and spleen. Injectable nano-carriers have important potential applications as in site-specific drug delivery.

• Aerosolized liposome-based delivery of amphotericin B to alveolar macrophages.

  Authors: Suresh P Vyas, Shama Quraishi, Swati Gupta, K S Jaganathan

  International journal of pharmaceutics. 06/2005; 296(1-2):12-25.

  The present study was aimed at preparation, characterization, and performance evaluation of amphotericin B (Amp B)-loaded aerosolized liposomes for their selective presentation to lungs (alveolarThe present study was aimed at preparation, characterization, and performance evaluation of amphotericin B (Amp B)-loaded aerosolized liposomes for their selective presentation to lungs (alveolar macrophages), that being the densest site of Aspergillosis infection. Egg phosphatidylcholine (PC)- and cholesterol (Chol)-based liposomes were modified by coating them with alveolar macrophage-specific ligands (O-palmitoyl mannan, OPM, and O-polmitoyl pullulan, OPP). The prepared formulations were characterized in vitro for vesicle morphology, mean vesicle size, vesicle size distribution and percent drug entrapment. Pressurized packed systems based on preformed liposomal formulations in chlorofluorocarbon aerosol propellants were prepared. In vitro airways penetration efficiency of the liposomal aerosols was determined by percent dose reaching the peripheral airways, it was recorded 1.4-1.6 times lower as compared to plain drug solution-based aerosol. In vivo tissue distribution studies on albino rats suggested the preferential accumulation of OPM- and OPP-coated formulations in the lung macrophages. Higher lung drug concentration was recorded in case of ligand-anchored liposomal aerosols as compared to plain drug solution and plain liposome-based aerosols. The drug was estimated in the lung in high concentration even after 24 h. The drug-localization index calculated after 6 h was nearly 1.42-, 4.47-, and 4.16-fold, respectively, for plain, OPM-, and OPP-coated liposomal aerosols as compared to plain drug solution-based aerosols. These results suggest that the ligand anchored liposomal aerosols are not only effective in rapid attainment of high-drug concentration in lungs with high population of alveolar macrophages but also maintain the same over prolonged period of time. The significance of targeting potential of the developed systems was established.

• Development of a single dose tetanus toxoid formulation based on polymeric microspheres: a comparative study of poly(D,L-lactic-co-glycolic acid) versus chitosan microspheres.

  Authors: K S Jaganathan, Y U B Rao, Paramjit Singh, D Prabakaran, Swati Gupta, Anubhav Jain, Suresh P Vyas

  International journal of pharmaceutics. 05/2005; 294(1-2):23-32.

  Stable polymeric microspheres capable of controlled release of tetanus toxoid (TT) for periods ranging from days to over months were developed. TT was stabilized, encapsulated in microspheresStable polymeric microspheres capable of controlled release of tetanus toxoid (TT) for periods ranging from days to over months were developed. TT was stabilized, encapsulated in microspheres prepared from poly(D,L)-lactide-co-glycolide (PLGA) and chitosan by using protein stabilizer (trehalose) and its immune response was compared. The influence of co-encapsulated protein stabilizer on tetanus toxoid's stability and release from the microspheres was studied. The protein stabilizer (trehalose) prevented structural losses and aggregation of microencapsulated TT. To neutralize the acids liberated by the biodegradable lactic/glycolic acid-based polymer, we also co-incorporated into the polymer an antacid, (Mg(OH)2), which neutralized the acidity during degradation of the polymer and also prevented TT structural losses and aggregation. The in vitro release experiments with PLGA and chitosan microspheres were performed and the release of TT was increased up to 80-90%. The antigen integrity was investigated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by coomassie brilliant blue staining. The SDS-PAGE analysis confirmed that antigen integrity was not affected by the encapsulation procedure. In addition, the immunogenicity of PLGA and chitosan microspheres based single dose vaccine was evaluated in guinea pigs and compared with multiple doses of alum adsorbed TT. Results indicated that a single injection of PLGA and chitosan microspheres containing TT could maintain the antibody response at a level comparable to the booster injections of conventional alum adsorbed vaccines. The both PLGA and chitosan based stable vaccine formulations produced an equal immune response. Hence chitosan can be used to replace the expensive polymer PLGA. This approach should have potential application in the field of vaccine delivery.

• Development of a single dose tetanus toxoid formulation based on polymeric microspheres: a comparative study of poly(d,l-lactic-co-glycolic acid) versus chitosan microspheres

  Authors: K.S. Jaganathan, Y.U.B. Rao, Paramjit Singh, D. Prabakaran, Swati Gupta, Anubhav Jain, Suresh P. Vyas

  International Journal of Pharmaceutics.

  Stable polymeric microspheres capable of controlled release of tetanus toxoid (TT) for periods ranging from days to over months were developed. TT was stabilized, encapsulated in microspheresStable polymeric microspheres capable of controlled release of tetanus toxoid (TT) for periods ranging from days to over months were developed. TT was stabilized, encapsulated in microspheres prepared from poly(d,l)-lactide-co-glycolide (PLGA) and chitosan by using protein stabilizer (trehalose) and its immune response was compared. The influence of co-encapsulated protein stabilizer on tetanus toxoid's stability and release from the microspheres was studied. The protein stabilizer (trehalose) prevented structural losses and aggregation of microencapsulated TT. To neutralize the acids liberated by the biodegradable lactic/glycolic acid-based polymer, we also co-incorporated into the polymer an antacid, (Mg(OH)2), which neutralized the acidity during degradation of the polymer and also prevented TT structural losses and aggregation. The in vitro release experiments with PLGA and chitosan microspheres were performed and the release of TT was increased up to 80–90%. The antigen integrity was investigated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by coomassie brilliant blue staining. The SDS-PAGE analysis confirmed that antigen integrity was not affected by the encapsulation procedure. In addition, the immunogenicity of PLGA and chitosan microspheres based single dose vaccine was evaluated in guinea pigs and compared with multiple doses of alum adsorbed TT. Results indicated that a single injection of PLGA and chitosan microspheres containing TT could maintain the antibody response at a level comparable to the booster injections of conventional alum adsorbed vaccines. The both PLGA and chitosan based stable vaccine formulations produced an equal immune response. Hence chitosan can be used to replace the expensive polymer PLGA. This approach should have potential application in the field of vaccine delivery.