HIV / AIDs

Recent Pat Antiinfect Drug Discov.   2012 Feb 17. [Epub ahead of print]

Safety and Efficacy of Setarud (IMOD(TM)) Among People Living with HIV/AIDS: A Review.

Paydary K, Emamzadeh-Fard S, Khorshid HR, Kamali K, Seyed Alinaghi S, Mohraz M.

Source

IRCHA, Imam Khomeini Hospital, Keshavarz Blvd., Tehran, Iran. s_a_alinaghi@yahoo.com

Abstract

The broad use of highly active anti-retroviral therapy (HAART), especially in developing world, has been associated with several problems such as
lactic acidosis, lipodistrophy, pancreatitis, hyperlipidemia, insulin resistance and hepatotoxicity. Extensive use of HAART has also resulted
in emergence of resistant HIV variants. Thereby, a pressing need for development of novel and cost-effective agents arises from these
limitations. Setarud (IMOD(TM)) is a safe, naturally-derived immunomodulator that was introduced for treatment of HIV patients in
Iran. It is prepared as a mixture of herbal extracts including Tanacetum vulgare (tansy), Rosa canina and Urtica dioica (nettle) in addition to
selenium, flavonoids and carotenes. Tanacetum vulgare may relieve anti-inflammatory symptoms and Rosa canina defers blood glucose and
cholesterol elevation. Extracts from Urtica dioica may prevent maturation of myeloid dendritic cells and reduce T cell responses. A
significant rise of CD4 count was observed in HIV patients treated by IMOD(TM) in clinical trial phases, which could be explained by its
immunomodulatory effects. Anti-oxidative activity of compounds in IMOD(TM) might play a role in the clinical outcomes of patients treated
with this drug. Moreover, IMOD(TM) may show improving activity upon lipid profile and liver metabolism. According to studies on IMOD(TM), it
seems that IMOD(TM) has minor side effects. IMOD(TM) with international publication number WO 2007/087825 A1 is an herbal extract which
includes Rosa canina, Urtica dioica, Tanacetum vulgare, and selenium comprising a treatment by pulsed electromagnetic field of high frequency
and is useful in treatment of HIV infection and AIDS. Int J Nanomedicine.  2010 Apr 7;5:157-66.

Magnetic nanoformulation of azidothymidine 5′-triphosphate for targeted delivery across the blood-brain barrier.

Saiyed ZM, Gandhi NH, Nair MP.

Source

Department of Immunology, College of Medicine, Florida International University, Miami, FL, USA.

Abstract

Despite significant advances in highly active antiretroviral therapy (HAART), the prevalence of neuroAIDS remains high. This is mainly attributed to inability of antiretroviral therapy (ART) to cross the blood-brain barrier (BBB), thus resulting in insufficient drug concentration within the brain. Therefore, development of an active drug targeting system is an attractive strategy to increase the efficacy and delivery of ART to the brain. We report herein development of magnetic azidothymidine 5′-triphosphate (AZTTP) liposomal nanoformulation and its ability to transmigrate across an in vitro BBB model by application of an external magnetic field. We hypothesize that this magnetically guided nanoformulation can transverse the BBB by direct transport or via monocyte-mediated transport. Magnetic AZTTP liposomes were prepared using a mixture of phosphatidyl choline and cholesterol. The average size of prepared liposomes was about 150 nm with maximum drug and magnetite loading efficiency of 54.5% and 45.3%, respectively. Further, magnetic AZTTP liposomes were checked for transmigration across an in vitro BBB model using direct or monocyte-mediated transport by application of an external magnetic field. The results show that apparent permeability of magnetic AZTTP liposomes was 3-fold higher than free AZTTP. Also, the magnetic AZTTP liposomes were efficiently taken up by monocytes and these magnetic monocytes showed enhanced transendothelial migration compared to normal/non-magnetic monocytes in presence of an external magnetic field. Thus, we anticipate that the developed magnetic nanoformulation can be used for targeting active nucleotide analog reverse transcriptase inhibitors to the brain by application of an external magnetic force and thereby eliminate the brain HIV reservoir and help to treat neuroAIDS. J Neurovirol.  2009 Jul;15(4):343-7.

AZT 5′-triphosphate nanoformulation suppresses human immunodeficiency virus type 1 replication in peripheral blood mononuclear cells.

Saiyed ZM, Gandhi NH, Nair MP.

Source

Department of Immunology, College of Medicine, Florida International University, Miami, Florida 33199, USA.

Abstract

Inefficient cellular phosphorylation of nucleoside and nucleotide analog reverse transcriptase inhibitors (NRTIs) to their active nucleoside 5′-triphosphate (NTPs) form is one of the limitations for human immunodeficiency virus (HIV) therapy. We report herein direct binding of 3′-azido-3′-deoxythymidine-5′-triphosphate (AZTTP) onto magnetic nanoparticles (Fe(3)O(4); magnetite) due to ionic interaction. This magnetic nanoparticle bound AZTTP (MP-AZTTP) completely retained its biological activity as assessed by suppression of HIV-1 replication in peripheral blood mononuclear cells. The developed MP-AZTTP nanoformulation can be used for targeting active NRTIs to the brain by application of an external magnetic force and thereby eliminate the brain HIV reservoir and help to treat NeuroAIDs.

Int J Pharm.  2008 Mar 3;351(1-2):271-81. Epub 2007 Sep 22.

Electromagnetic interference in the permeability of saquinavir across the blood-brain barrier using nanoparticulate carriers.

Kuo YC, Kuo CY.

Source

Department of Chemical Engineering, National Chung Cheng University, Chia-Yi, Taiwan 62102, Republic of China. chmyck@ccu.edu.tw

Abstract

Transport of antiretroviral agents across the blood-brain barrier (BBB) is of key importance to the treatment for the acquired immunodeficiency syndrome (AIDS). In this study, impact of exposure to electromagnetic field (EMF) on the permeability of saquinavir (SQV) across BBB was investigated. The in vitro BBB model was based on human brain-microvascular endothelial cells (HBMEC), and the concentration of SQV in receiver chamber of the transport system was evaluated. Polybutylcyanoacrylate (PBCA), methylmethacrylate-sulfopropylmethacrylate (MMA-SPM), and solid lipid nanoparticle (SLN) were employed as carriers for the delivery systems. Cytotoxicity of SLN decreased as content of cacao butter increased. Power of 5mV was apposite for the study on HBMEC without obvious apoptosis. Square wave produced greater permeability than sine and triangle waves. The carrier order on permeability of SQV across HBMEC monolayer under exposure to EMF was SLN>PBCA>MMA-SPM. Also, a larger frequency, modulation or depth of amplitude modulation (AM), or modulation or deviation of frequency modulation (FM) yielded a greater permeability. Besides, enhancement of permeability by AM wave was more significant than that by FM wave. Transport behavior of SQV across BBB was strongly influenced by the combination of nanoparticulate PBCA, MMA-SPM, and SLN with EMF exposure. This combination would be beneficial to the clinical application to the therapy of AIDS and other brain-related diseases. Panminerva Med. 1995 Mar;37(1):22-7.

A magnetic approach to AIDS.

Jacobson JI Source

Institute of Theoretical Physics and Advanced Studies for Biophysical Res, Jupiter, FL 334377-1418, USA.

Abstract

Jacobson Resonance is the unified field equation yielding a frontier vision in magnetotherapy. The possible application to AIDS is considered.