Abstract:
OBJECTIVES:Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor, is a drug that is frequently included in highly active antiretroviral therapy for treatment of HIV infection. Decreased bioavailability and increased toxicity limit its use. We report a formulation of efavirenz-loaded lactoferrin nanoparticles (lacto-EFV-nano) for oral delivery which exhibited significantly improved pharmacological properties coupled with reduced toxicity compared with its free form. METHODS:Lacto-EFV-nano was prepared using the Sol-oil protocol and characterized using various sources of characterization. In vitro and in vivo studies were performed to test the stability, safety, efficacy, biodistribution and pharmacokinetics of lacto-EFV-nano. RESULTS:The nanoparticles prepared for the present study had an average size of 45-60 nm as revealed by field emission scanning electron microscope measurements. Further, dynamic light scattering data showed a hydrodynamic radius of 103 ± 5.3 nm, a zeta potential of -23 ± 1.2 mV and a polydispersity index of < 0.341. Lacto-EFV-nano was found to be stable as assessed using differential scanning calorimetry and Fourier-transform infrared spectroscopy. Cell viability studies showed that lacto-EFV-nano was at least 2-fold less toxic to peripheral blood mononuclear cells, Jurkat T cell and B16-F10 cell lines than free EFV. Furthermore, lacto-EFV-nano [50% inhibitory concentration (IC50 ) < 1.1 nM] showed > 2-fold enhanced anti-HIV-1 activity compared with free EFV (IC50 = 2.56 nM). Lacto-EFV-nano exhibited improved oral bioavailability and an improved in vivo pharmacokinetic profile, with a > 3-4-fold increase in the area under the plasma concentration-time curve (AUC), a 6-7-fold increase in the area under the first moment curve (AUMC), a > 30% increase in the peak plasma concentration of the drug after oral administration (Cmax ) and a 2-fold increase in the time to reach Cmax (Tmax ) and the time required for the concentration of the drug to reach half of its original value (t1/2 ). Furthermore, lacto-EFV-nano did not show any organ-related toxicity. A significant decrease in the concentrations of various parameters, elevated concentrations of which are markers of reduced safety, were also observed in rats treated with lacto-EFV-nano. CONCLUSIONS:Compared with free EFV, lacto-EFV-nano is a promising oral nanoformulation with enhanced bioavailability and efficacy of EFV and improved safety.
journal_name
HIV Medjournal_title
HIV medicineauthors
Kumar P,Lakshmi YS,Kondapi AKdoi
10.1111/hiv.12475subject
Has Abstractpub_date
2017-08-01 00:00:00pages
452-462issue
7eissn
1464-2662issn
1468-1293journal_volume
18pub_type
杂志文章相关文献
HIV MEDICINE文献大全abstract:OBJECTIVES:Anaemia represents a common toxicity with amphotericin B-based induction therapy in HIV-infected persons with cryptococcal meningitis. We sought to examine the impact of amphotericin-related anaemia on survival. METHODS:We used data from Ugandan and South African trial participants to characterize the varia...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1111/hiv.12387
更新日期:2017-01-01 00:00:00
abstract:OBJECTIVES:Virological failure on first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based treatment regimens has become a problem in HIV-infected children on long-term antiretroviral therapy (ART). Protease inhibitor (PI)-based regimens are therefore often given to children failing NNRTI-based regimens. ...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1111/j.1468-1293.2012.01061.x
更新日期:2013-04-01 00:00:00
abstract:OBJECTIVES:HIV infection and its treatment are associated with dyslipidaemia and increased risk of cardiovascular disease. Accurate high-density lipoprotein (HDL) cholesterol values are necessary for the management of these abnormalities, but current methods have not been properly assessed in these patients. The aim of...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1111/j.1468-1293.2009.00772.x
更新日期:2010-04-01 00:00:00
abstract:OBJECTIVES:Despite adequate suppression of plasma HIV RNA, viral escape in cerebrospinal fluid (CSF) is widely reported. Rates of CSF HIV RNA escape vary in the literature. In persons living with HIV (PLWH) undergoing lumbar puncture examination for clinical reasons, we assessed rates of CSF HIV RNA escape. METHODS:Pe...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1111/hiv.12594
更新日期:2018-05-01 00:00:00
abstract:OBJECTIVE:The aim of the study was to describe Veterans Healthcare Administration (VHA) system-wide uptake of three HIV protease inhibitors: atazanavir, darunavir and tipranavir. METHODS:This retrospective cohort study evaluated VHA uptake of three target antiretrovirals and lopinavir/ritonavir in each complete 90-day...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1111/j.1468-1293.2009.00764.x
更新日期:2010-03-01 00:00:00
abstract:OBJECTIVES:We examined whether insulin-resistant lipodystrophic HIV-infected patients with known high fasting prehepatic insulin secretion rates (FISRs) displayed alterations in first-phase prehepatic insulin response to intravenous glucose (ISREG0-10 min). METHODS:Eighteen normoglycaemic lipodystrophic HIV-infected (...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1111/j.1468-1293.2006.00364.x
更新日期:2006-04-01 00:00:00
abstract:OBJECTIVE:To assess the incidence and consequences of adverse reactions among African HIV-positive pregnant women treated with fixed-dose combinations of a nevirapine-containing antiretroviral (ARV) triple therapy. METHODS:A retrospective analysis of the clinical files of 703 HIV-1-positive pregnant women treated with...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1111/j.1468-1293.2006.00386.x
更新日期:2006-07-01 00:00:00
abstract:OBJECTIVE:To assess adherence to the British HIV Association (BHIVA) 2001 guidelines for the management of HIV-infected pregnant women. METHODS:A survey and a case note review were carried out using structured questionnaires sent to providers of adult HIV care in the UK and Ireland. Participants were women with HIV in...
journal_title:HIV medicine
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1468-1293.2006.00385.x
更新日期:2006-07-01 00:00:00
abstract:OBJECTIVES:To determine whether HIV-infected mothers knew the HIV status of their children, enabling the offer of targeted testing of children at risk. METHODS:All HIV-positive women attending the genitourinary medicine clinic at a district general hospital in the United Kingdom were asked whether they had children an...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1111/j.1468-1293.2008.00556.x
更新日期:2008-04-01 00:00:00
abstract:OBJECTIVES:The aim of the study was to describe the prevalence of and examine the factors associated with immunosuppression (CD4 < 200 cells/microL) among HIV-infected patients attending two large inner London treatment centres. METHODS:Patients attending for care who had a CD4 count < 200 cells/microL during a 6-mont...
journal_title:HIV medicine
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1468-1293.2009.00753.x
更新日期:2010-02-01 00:00:00
abstract:OBJECTIVE:Study 903 was a 144-week, randomized, double-blind, active-controlled study of tenofovir disoproxil fumarate (TDF) therapy in treatment-naive HIV-1-infected patients. Patients received either TDF (n = 299) or stavudine (d4T) (n = 301) with lamivudine (3TC) and efavirenz (EFV). Resistance analyses were perform...
journal_title:HIV medicine
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1468-1293.2006.00404.x
更新日期:2006-10-01 00:00:00
abstract:OBJECTIVES:Few studies have explored the optimal dosing for efavirenz in individuals from China. We investigated plasma efavirenz concentrations and their association with efficacy and tolerance of efavirenz 600 mg daily in Chinese HIV-infected adults. METHODS:An analysis was performed using plasma samples from 455 pa...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1111/hiv.12607
更新日期:2018-05-15 00:00:00
abstract:OBJECTIVES:To assess second-line antiretroviral therapy (ART) virological failure and HIV drug resistance-associated mutations (RAMs), in support of third-line regimen planning in Asia. METHODS:Adults > 18 years of age on second-line ART for ≥ 6 months were eligible. Cross-sectional data on HIV viral load (VL) and gen...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1111/hiv.13006
更新日期:2020-11-05 00:00:00
abstract:OBJECTIVES:To compare the safety and efficacy of amprenavir [APV/j Agenerase trade mark; GlaxoSmithKline, [Ware, UK; 600 mg twice a day (bid)] boosted with low-dose ritonavir (RTV, 100 mg bid) with those of other protease inhibitors (PIs) in PI-experienced HIV-infected patients. STUDY DESIGN:Parallel-group, randomized...
journal_title:HIV medicine
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1111/j.1468-1293.2004.00224.x
更新日期:2004-07-01 00:00:00
abstract:BACKGROUND:AIDS-related lymphoma (ARL) remains the main cause of AIDS-related deaths in the combined antiretroviral therapy (cART) era. Although most ARLs are associated with the Epstein-Barr virus (EBV), whether patients with high EBV burden are more at risk of developing ARL is unknown. This study investigated the re...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1111/j.1468-1293.2012.00998.x
更新日期:2012-09-01 00:00:00
abstract:OBJECTIVE:This study was designed to evaluate the effects of the HIV protease inhibitor lopinavir/ritonavir on gingival epithelium growth, integrity and differentiation. METHODS:Organotypic (raft) cultures of gingival keratinocytes were established and treated with a range of lopinavir/ritonavir concentrations. To exa...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1111/j.1468-1293.2010.00863.x
更新日期:2011-03-01 00:00:00
abstract:OBJECTIVES:Across Europe, almost a third of individuals infected with HIV do not enter health care until late in the course of their infection. Surveillance to identify the extent to which late presentation occurs remains inadequate across Europe and is further complicated by the lack of a common clinical definition of...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1111/j.1468-1293.2010.00857.x
更新日期:2011-01-01 00:00:00
abstract:OBJECTIVES:To study the impact of highly active antiretroviral therapy (HAART) on isotype switching and avidity maturation of HIV-1-specific immunoglobulin G (IgG) in patients with primary HIV-1 infection (PHI). METHODS:We studied the emergence and the evolution of anti-HIV IgG antibodies by quantitative immunoblottin...
journal_title:HIV medicine
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1468-1293.2006.00406.x
更新日期:2006-11-01 00:00:00
abstract:OBJECTIVES:The relationship between marijuana use and markers of chronic lung disease in people living with HIV (PLWH) is poorly understood. METHODS:We performed a cross-sectional analysis of the Examinations of HIV-Associated Lung Emphysema (EXHALE) study, including 162 HIV-positive patients and 138 participants with...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1111/hiv.12966
更新日期:2021-02-01 00:00:00
abstract:OBJECTIVES:The extent to which highly active antiretroviral therapy (HAART) affects human papillomavirus (HPV) acquisition and clearance in HIV-infected women is not well understood. We sought to describe high-risk HPV detection and clearance rates over time since HAART initiation, based on time-varying HIV viral load ...
journal_title:HIV medicine
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1468-1293.2011.00979.x
更新日期:2012-07-01 00:00:00
abstract::Worldwide we have seen dramatic increases in HIV prevalence and decreases in life expectancy over the last decade. The aim of this study was to determine the association between HIV prevalence and life expectancy. A strong negative association between adult HIV prevalence and life expectancy was observed for 137 count...
journal_title:HIV medicine
pub_type: 信件
doi:10.1111/j.1468-1293.2005.00266.x
更新日期:2005-03-01 00:00:00
abstract:OBJECTIVES:Certain non-AIDS-related diseases have been associated with immunodeficiency and HIV RNA levels in HIV-infected patients on combination antiretroviral therapy (cART). We aimed to investigate these associations in patients not yet on cART, when potential antiretroviral-drug-related effects are absent and vari...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1111/hiv.12202
更新日期:2015-05-01 00:00:00
abstract:OBJECTIVE:To document the demographic changes in new HIV diagnoses at the Royal Free Hospital, London, UK, between 1994 and 2000. DESIGN:Retrospective case note review. METHODS:Data were extracted from the Royal Free HIV database identifying new diagnoses for 1994, 1997 and 2000. All case notes were reviewed and pati...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1046/j.1468-1293.2002.00103.x
更新日期:2002-04-01 00:00:00
abstract:OBJECTIVES:Conflicting results have been reported regarding the ability of valproic acid (VPA) to reduce the size of HIV reservoirs in patients receiving suppressive highly active antiretroviral therapy (HAART). In a randomized multicentre, cross-over study, we assessed whether adding VPA to stable HAART could potentia...
journal_title:HIV medicine
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1111/j.1468-1293.2011.00975.x
更新日期:2012-05-01 00:00:00
abstract:OBJECTIVES:Despite the availability of HIV testing guidelines to facilitate prompt diagnosis, late HIV diagnosis remains high across Europe. The study synthesizes recent evidence on HIV testing strategies adopted in health care settings in the European Union/European Economic Area (EU/EEA). METHODS:Preferred Reporting...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1111/hiv.12809
更新日期:2020-03-01 00:00:00
abstract:OBJECTIVES:The perceived threat of HIV transmission through spitting and biting is evidenced by the increasing use of "spit hoods" by Police Forces in the UK. In addition, a draft parliamentary bill has called for increased penalties for assaults on emergency workers, citing the risk of communicable disease transmissio...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1111/hiv.12625
更新日期:2018-04-23 00:00:00
abstract::We report the case of an asthmatic man with HIV infection who was initially diagnosed with HIV treatment-associated lipodystrophy. Further investigations showed he had Cushing's syndrome secondary to 1600 microg of budesonide dry powder inhaler. Cushing's syndrome has not been reported previously on this normal dose o...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1046/j.1468-1293.2001.00058.x
更新日期:2001-04-01 00:00:00
abstract:OBJECTIVES:Antiretroviral therapy (ART) has been associated with unfavourable lipid profile changes and increased risk of cardiovascular disease (CVD). With a growing population on ART in South Africa, there has been concern about the increase in noncommunicable diseases such as CVD. We determined risk factors associat...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1111/hiv.12495
更新日期:2017-09-01 00:00:00
abstract:OBJECTIVES:Dyslipidaemia has become a common problem in HIV disease, especially in patients on current antiretroviral therapy. However, the pathogenic mechanisms involved are not well understood or documented using conventional lipid measurements. METHODS:Using a cross-sectional design, the prevalence of abnormal stan...
journal_title:HIV medicine
pub_type: 杂志文章,多中心研究
doi:10.1111/j.1468-1293.2005.00316.x
更新日期:2005-09-01 00:00:00
abstract::Despite advances in the treatment of HIV disease, the incidence and mortality of invasive cryptococcal disease remain significant. A matched, case-control study was performed to examine the impact of highly active antiretroviral therapy (HAART) and azole use on the incidence of invasive cryptococcal disease in HIV-inf...
journal_title:HIV medicine
pub_type: 杂志文章
doi:10.1111/j.1468-1293.2005.00289.x
更新日期:2005-07-01 00:00:00