Mannose-conjugated chitosan nanoparticles loaded with rifampicin for the treatment of visceral leishmaniasis

Chaubey, Pramila; Mishra, Brahmeshwar

doi:10.1016/j.carbpol.2013.10.044

Cited by 162 publications

(71 citation statements)

References 32 publications

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“…41 It is already reported that Schiff's bases may remain in an equilibrium stage by reduction of the secondary amine, especially in lower pH. In the spectra of M-SLNs, the presence of N-H bending of secondary amines at 1,558.56 cm -1 and C=N stretch at 1,410.01 cm -1 are observed, 13,41,57,58 confirming the formation of the Schiff's base and the linkage between mannose and amine termination present in SA in the SLNs.…”

Section: ° °mentioning

confidence: 92%

Design and statistical modeling of mannose-decorated dapsone-containing nanoparticles as a strategy of targeting intestinal M-cells

Vieira¹,

Chaves²,

Pinheiro³

et al. 2016

IJN

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The aim of the present work was to develop and optimize surface-functionalized solid lipid nanoparticles (SLNs) for improvement of the therapeutic index of dapsone (DAP), with the application of a design of experiments. The formulation was designed to target intestinal microfold (M-cells) as a strategy to increase internalization of the drug by the infected macrophages. DAP-loaded SLNs and mannosylated SLNs (M-SLNs) were successfully developed by hot ultrasonication method employing a three-level, three-factor Box–Behnken design, after the preformulation study was carried out with different lipids. All the formulations were systematically characterized regarding their diameter, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, and loading capacity. They were also subjected to morphological studies using transmission electron microscopy, in vitro release study, infrared analysis (Fourier transform infrared spectroscopy), calorimetry studies (differential scanning calorimetry), and stability studies. The diameter of SLNs, SLN-DAP, M-SLNs, and M-SLN-DAP was approximately 300 nm and the obtained PDI was <0.2, confirming uniform populations. Entrapment efficiency and loading capacity were approximately 50% and 12%, respectively. Transmission electron microscopy showed spherical shape and nonaggregated nanoparticles. Fourier transform infrared spectroscopy was used to confirm the success of mannose coating process though Schiff’s base formation. The variation of the ZP between uncoated (approximately −30 mV) and mannosylated formulations (approximately +60 mV) also confirmed the successful coating process. A decrease in the enthalpy and broadening of the lipid melting peaks of the differential scanning calorimetry thermograms are consistent with the nanostructure of the SLNs. Moreover, the drug release was pH-sensitive, with a faster drug release at acidic pH than at neutral pH. Storage stability for the formulations for at least 8 weeks is expected, since they maintain the original characteristics of diameter, PDI, and ZP. These results pose a strong argument that the developed formulations can be explored as a promising carrier for treating leprosy with an innovative approach to target DAP directly to M-cells.

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Section: ° °mentioning

confidence: 92%

Design and statistical modeling of mannose-decorated dapsone-containing nanoparticles as a strategy of targeting intestinal M-cells

Vieira¹,

Chaves²,

Pinheiro³

et al. 2016

IJN

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“…Actively targeting nanoparticles to alveolar macrophages has been extensively investigated for treatment of various infections associated with tuberculosis, visceral leishmaniasis, arthritis, etc. [240][241][242]. Gelatin nanoparticles encapsulating isoniazid with and without mannose conjugated to the surface of nanoparticles, required for selective delivery to macrophages, have been studied.…”

Section: Macrophage Targetingmentioning

confidence: 99%

A New Era of Pulmonary Delivery of Nano-antimicrobial Therapeutics to Treat Chronic Pulmonary Infections

Merchant

Buckton²,

Taylor³

et al. 2016

CPD

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Pulmonary infections may be fatal especially in immunocompromised patients and patients with underlying pulmonary dysfunction, such as those with cystic fibrosis, chronic obstructive pulmonary disorder, etc. According to the WHO, lower respiratory tract infections ranked first amongst the leading causes of death in 2012, and tuberculosis was included in the top 10 causes of death in low income countries, placing a considerable strain on their economies and healthcare systems. Eradication of lower respiratory infections is arduous, leading to high healthcare costs and requiring higher doses of antibiotics to reach optimal concentrations at the site of pulmonary infection for protracted periods. Hence direct inhalation to the respiratory epithelium has been investigated extensively in the past decade, and seems to be an attractive approach to eradicate and hence overcome this widespread problem. Moreover, engineering inhalation formulations wherein the antibiotics are encapsulated within nanoscale carriers could serve to overcome many of the limitations faced by conventional antibiotics, like difficulty in treating intracellular pathogens such as mycobacteria spp. and salmonella spp., biofilmassociated pathogens like Pseudomonas aeruginosa and Staphylococcus aureus, passage through the sputum associated with disorders like cystic fibrosis and chronic obstructive pulmonary disorder, systemic side effects following oral/parenteral delivery and inadequate concentrations of antibiotic at the site of infection leading to resistance. Encapsulation of antibiotics in nanocarriers may help in providing a protective environment to combat antibiotic degradation, confer controlled-release properties, hence reducing dosing frequency, and may increase uptake via specific and non-specific targeting modalities. Hence nanotechnology combined with direct administration to the airways using commercially available delivery devices, is a highly attractive formulation strategy to eradicate microorganisms from the lower respiratory tract, which might otherwise present opportunities for multi-drug resistance.

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“…New formulations of nanoparticles and Amp B have been used with varying results in hamsters infected with VL. These formulations include phosphoserine-coated gelatin nanoparticles coupled with Amp B, PLGA-Peg encapsulated Amp B nanoparticles and Amp B-encapsulated chitosan nanocapsules, which also worked as an immunoadjuvant in up-regulating tumor necrosis factor, IL-12, and iNOS [12]. Combination therapy for VL in humans has shown good activity for these combinations: AmBisome+miltefosine, paromomycin+miltefosine and antimonials+paromomycin [13].…”

Section: Novel Approachesmentioning

confidence: 99%

A Targeted and Adjuvanted Nanoparticle for Immunochemotherapy of Leishmania Infections

2014

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Targeted drug delivery is critical for minimizing off-target toxicity by chemotherapeutic drugs. Amphotericin-B is an effective anti-leishmaniasis agent that induces significant nephrotoxicity. Complexing amphotericin-B with liposomes (AmBisome, LAmB) reduces nephrotoxicity and improves LAmB efficacy in treating leishmaniasis in humans. However, complicated dosing regimens are required to minimize side effects. Given that Leishmania species are obligate parasites in phagocytes, selectively targeting LAmB to infected phagocytes would likely improve efficacy, decrease systemic toxicity, and simplify dosing regimens. To target LAmB to phagocytes, we developed a PADREderivatized-dendrimer (PDD)-LAmB nanocarrier platform by functionalizing dendrimers that complex LAmB with a peptide that targets major histocompatibility complex (MHC) class II receptors. MHC class II receptor expression increases on phagocytes during the course of leishmaniasis, further enhancing infected cells as targets for PDD-LAmB. In a murine model for Leishmania major infection, PDD-LAmB efficiently targeted infected phagocytic cells, reducing the LAmB effective dose by 80 %, with improved pharmacokinetics. Moreover, the PDD MHC class II-targeting peptide is a universal helper T-cell epitope, allowing PDD-LAmB complexes to elicit parasite-specific T-cell responses. Thus, PDD-LAmB complex is a promising candidate for further development and human clinical trials, reducing and simplifying LAmB dosing, reducing side effects, and stimulating Tcell responses.

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Mannose-conjugated chitosan nanoparticles loaded with rifampicin for the treatment of visceral leishmaniasis

Cited by 162 publications

References 32 publications

Design and statistical modeling of mannose-decorated dapsone-containing nanoparticles as a strategy of targeting intestinal M-cells

Design and statistical modeling of mannose-decorated dapsone-containing nanoparticles as a strategy of targeting intestinal M-cells

A New Era of Pulmonary Delivery of Nano-antimicrobial Therapeutics to Treat Chronic Pulmonary Infections

A Targeted and Adjuvanted Nanoparticle for Immunochemotherapy of Leishmania Infections

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