Pharmacokinetic Evaluation of Wheat Germ Agglutinin-Grafted Nanoparticles of Mometasone Furoate

The aim of the investigation was to assess the pharmacokinetic parameters of wheat germ agglutinin (WGA)-grafted nanoparticles of mometasone furoate (MF), after intratracheal instillation in rats. PLGA (50:50) nanoparticles (NPs) loaded with MF were prepared by emulsion-solvent evaporation technique. WGA was conjugated to spherical MF loaded nanoparticles by carbodiimide coupling yielding a ligand density of 10-15μg WGA / mg NP. The nanoparticles were characterized for size, zeta potential, entrapment efficiency and in-vitro drug release. Plain drug, MF nanoparticles and WGA-grafted MF nanoparticles were administered intratracheally in rats and at different time intervals drug levels in the lung tissue and bronchoalveolar lavage (BAL) were estimated using HPLC. Cumulative MF-release from unconjugated and conjugated MFnanoparticles after 2 weeks was 68% and 55% of the initial drug loading. From the lung MF concentration vs time plot, AUC for WGA-MF-NPs and MF-NPs was found to be 5.9 and 3.8 times higher than AUC for plain MF. This improvement of intracellular drug uptake by means of WGA-conjugation might be due to bioadhesive nature of the lectin which provides an intimate contact to lung mucosal cells followed by facilitated transcytosis as confirmed by improved pharmacokinetic behaviour. All in all, these findings are expected to contribute for better management of asthma to overcome the limitation of short lived action associated with dry powder inhalers

Clobetasol propionate solid lipid nanoparticles cream for effective treatment of eczema: Formulation and clinical implications

233-240In the present study clobetasol propionate (Cp) was loaded as solid lipid nanoparticles (SLN), incorporated it in suitable cream base and evaluated in vitro and its performance clinically against equivalent marketed formulation. Cp was incorporated into SLN by high-pressure homogenization technique and characterized for mean particle size, surface morphology and per cent drug entrapment. Drug permeation and skin uptake studies from Cp creams were carried out in a validated Franz static diffusion cell across human cadaver skin (HCS). Sixteen chronic eczema patients were enrolled in a controlled double blind clinical trial. Optimized Cp-SLN was smooth and spherical under scanning electron microscopy; with average particle size of 177 nm and per cent drug entrapment of 92.05%. In vitro permeation studies revealed lower mean flux value and higher skin uptake of Cp from Cp-SLN cream compared to marketed drug cream. Both formulations were found to be responsive to manifestations of chronic eczema, while Cp-SLN cream prepared in this investigation registered significant improvement in therapeutic response (1.9 fold ; inflammation, 1.2 fold; itching) in terms of per cent reduction in degree of inflammation and itching against marketed cream. Further clinical trials are required to ascertain the efficiency of the present formulation

Systematic Approach for the Formulation and Optimization of Solid Lipid Nanoparticles of Efavirenz by High Pressure Homogenization Using Design of Experiments for Brain Targeting and Enhanced Bioavailability

The nonnucleoside reverse transcriptase inhibitors, used for the treatment of HIV infections, are reported to have low bioavailability pertaining to high first-pass metabolism, high protein binding, and enzymatic metabolism. They also show low permeability across blood brain barrier. The CNS is reported to be the most important HIV reservoir site. In the present study, solid lipid nanoparticles of efavirenz were prepared with the objective of providing increased permeability and protection of drug due to biocompatible lipidic content and nanoscale size and thus developing formulation having potential for enhanced bioavailability and brain targeting. Solid lipid nanoparticles were prepared by high pressure homogenization technique using a systematic approach of design of experiments (DoE) and evaluated for particle size, polydispersity index, zeta potential, and entrapment efficiency. Particles of average size 108.5 nm having PDI of 0.172 with 64.9% entrapment efficiency were produced. Zeta potential was found to be −21.2 mV and the formulation was found stable. The in-vivo pharmacokinetic studies revealed increased concentration of the drug in brain, as desired, when administered through intranasal route indicating its potential for an attempt towards complete eradication of HIV and cure of HIV-infected patients

Association of Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Thyroglobulin (TG) Genetic Variants with Autoimmune Hypothyroidism.

Autoimmune hypothyroidism is known to be caused by immune responses related to the thyroid gland and its immunological feature includes presence of autoimmune antibodies. Therefore the aim was to analyze presence of anti-TPO antibodies in hypothyroidism patients in Gujarat. Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) is one of the susceptibility genes for various autoimmune diseases. Hence, exon1 +49A/G and 3'UTR CT60A/G single nucleotide polymorphisms (SNPs) in CTLA4 and its mRNA expression levels were investigated in autoimmune hypothyroidism patients. Thyroglobulin (TG) is known to be associated with autoimmune thyroid disorders and thus exon 33 (E33) SNP in TG was investigated. We analyzed the presence of anti-TPO antibodies in the plasma samples of 84 hypothyroidism patients and 62 controls by ELISA. PCR-RFLP technique was used for genotyping of polymorphisms. sCTLA4 and flCTLA4 mRNA expression levels were assessed by real time PCR. 59.52% of hypothyroid patients had anti-TPO antibodies in their circulation. The genotype and allele frequencies differed significantly for +49A/G (p = 0.0004 for +49AG, p = 0.0019 for +49GG & p = 0.0004 for allele), CT60 (p = 0.0110 for CT60AG, p = 0.0005 for CT60GG & p<0.0001 for allele) and TG E33 (p = 0.0003 for E33TC p<0.0001 for E33CC& p<0.0001 for allele) SNPs between patients and controls. Patients had significantly decreased mRNA levels of both sCTLA4 (p = 0.0017) and flCTLA4 (p<0.0001) compared to controls. +49A/G and CT60 polymorphisms of CTLA4 were in moderate linkage disequilibrium. Logistic regression analysis indicated significant association of CT49A/G, CT60A/G and TG exon 33 polymorphisms with susceptibility to autoimmune hypothyroidism when adjusted for age and gender. Our results suggest +49A/G and CT60 polymorphism of CTLA4 and E33 polymorphism of TG may be genetic risk factors for autoimmune hypothyroidism susceptibility and down regulation of both forms of CTLA4 advocates the crucial role of CTLA4 in pathogenesis of autoimmune hypothyroidism

Association of Cytotoxic T-Lymphocyte Antigen 4 (<i>CTLA4</i>) and Thyroglobulin (<i>TG</i>) Genetic Variants with Autoimmune Hypothyroidism - Fig 4

<p><b>Ratio of s<i>CTLA4</i> and fl<i>CTLA4</i> mRNA expression with respect to +49A/G and CT60A/G genotypes in controls and patients: (A)</b> s<i>CTLA4</i>/fl<i>CTLA4</i> mRNA ratio was analyzed with respect to +49A/G genotypes in patients and controls. None of AA, AG and GG genotypes showed significant difference in the s<i>CTLA4</i>/fl<i>CTLA4</i> mRNA ratio in patients compared to controls (<i>p</i> = 0.9724, <i>p</i> = 0.2378 and <i>p</i> = 0.3405 respectively). [<i>NS</i> = non-significant] <b>(B)</b> s<i>CTLA4</i>/fl<i>CTLA4</i> mRNA ratio was analyzed with respect to CT60A/G genotypes in patients and controls. None of AA, AG and GG genotypes showed significant difference in the s<i>CTLA4</i>/fl<i>CTLA4</i> mRNA ratio in patients compared to controls (<i>p</i> = 0.6213, <i>p</i> = 0.4425 and <i>p</i> = 0.2940 respectively). [<i>NS</i> = non-significant].</p