BackgroundThe treatment of AIDS remains a serious challenge owing to high genetic variation of Human Immunodeficiency Virus type 1 (HIV-1). The use of different antiretroviral drugs (ARV) is significantly limited by severe side-effects that further compromise the quality of life of the AIDS patient. In the present study, we have evaluated a liposome system for the delivery of nevirapine, a hydrophobic non-nucleoside reverse transcriptase inhibitor. Liposomes were prepared from egg phospholipids using thin film hydration. The parameters of the process were optimized to obtain spherical liposomes below 200 nm with a narrow polydispersity. The encapsulation efficiency of the liposomes was optimized at different ratios of egg phospholipid to cholesterol as well as drug to total lipid. The data demonstrate that encapsulation efficiency of 78.14% and 76.25% were obtained at egg phospholipid to cholesterol ratio of 9:1 and drug to lipid ratio of 1:5, respectively. We further observed that the size of the liposomes and the encapsulation efficiency of the drug increased concomitantly with the increasing ratio of drug and lipid and that maximum stability was observed at the physiological pH. Thermal analysis of the drug encapsulated liposomes indicated the formation of a homogenous drug-lipid system. The magnitude of drug release from the liposomes was examined under different experimental conditions including in phosphate buffered saline (PBS), Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 10% fetal bovine serum or in the presence of an external stimulus such as low frequency ultrasound. Within the first 20 minutes 40, 60 and 100% of the drug was released when placed in PBS, DMEM or when ultrasound was applied, respectively. We propose that nevirapine-loaded liposomal formulations reported here could improve targeted delivery of the anti-retroviral drugs to select compartments and cells and alleviate systemic toxic side effects as a consequence.
Human Immunodeficiency Virus (HIV) infection remains a significant cause of mortality globally. Though antiretroviral therapy has significantly reduced AIDS-related morbidity and mortality, there are several drawbacks in the current therapy, including toxicity, drug-drug interactions, development of drug resistance, necessity for long-term drug therapy, poor bio-availability and lack of access to tissues and reservoirs. To circumvent these problems, recent anti-HIV therapeutic research has focused on improving drug delivery systems through drug delivery targeted specifically to host cells infected with HIV or could potentially get infected with HIV. In this regard, several surface molecules of both viral and host cell origin have been described in recent years, that would enable targeted drug delivery in HIV infection. In the present review, we provide a comprehensive overview of the need for novel drug delivery systems, and the successes and challenges in the identification of novel viral and host-cell molecules for the targeted drug delivery of anti-HIV drugs. Such targeted anti-retroviral drug delivery approaches could pave the way for effective treatment and eradication of HIV from the body.
Electrospun nanofibrous scaffolds have gained momentum in regenerative medicine research due to their ECM-like architecture. The present study reports the fabrication of mesoporous silica nanofibers (MSF) and explores its potential to trigger osteogenic differentiation of human bone marrow derived mesenchymal stem cells (BM-MSCs) in presence and absence of biochemical (induction) factors. BM-MSCs were seeded on MSF and allowed to differentiate into osteogenic lineage. Osteogenic differentiation of BM-MSCs was confirmed by mineralization staining, reduction in the expression of the stem cell marker CD105 and increase in the osteogenic marker osteocalcin. Cells cultured in MSF in presence of induction media exhibited better adhesion, proliferation and differentiation. The phenotypic markers of osteoblasts such as mineralization and alkaline phosphatase (ALP) activity were higher on MSF in presence of induction media when compared to MSF in presence of normal media (p<0.05). Upregulation of osteoblast specific genes (osteonectin, osteocalcin & alkaline phosphatase) suggest the potential of MSF to support osteogenic differentiation even in the absence of induction media (p<0.05). In vitro results indicate that the nanotopography of MSF provided a favorable milieu for adhesion and proliferation of BM-MSCs. Further, the combination of biomimetic nature of MSF, dissolution ions of silica (chemical cues) and biochemical cues presents a stable microenvironment for the differentiation of BM-MSCs into osteogenic lineage. In conclusion, the synergy of adhesion and proliferation cues in MSF along with a suitable biochemical cues could be a promising design strategy to develop scaffolds for orchestrated bone healing.
Carboxylated graphene quantum dots (cGQDs) were synthesized from dextrose and sulfuric acid via a hydrothermal process, and subsequently used as sole surfactant in miniemulsion polymerization of styrene.
Graphene quantum dots (GQDs) continue to draw interest in biomedical applications. However, their efficacy gets compromised due to their rapid clearance from body. On one side, rapid clearance is desired...
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