11 results on '"Godse, Sandip"'
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2. Extracellular vesicles released from macrophages modulates interleukin-1β in astrocytic and neuronal cells
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Kodidela, Sunitha, Sinha, Namita, Kumar, Asit, Zhou, Lina, Godse, Sandip, and Kumar, Santosh
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- 2023
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3. LM11A-31, a modulator of p75 neurotrophin receptor, suppresses HIV-1 replication and inflammatory response in macrophages.
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Mirzahosseini, Golnoush, Sinha, Namita, Zhou, Lina, Godse, Sandip, Kodidela, Sunitha, Singh, Udai P., Ishrat, Tauheed, and Kumar, Santosh
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- 2024
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4. Darunavir Nanoformulation Suppresses HIV Pathogenesis in Macrophages and Improves Drug Delivery to the Brain in Mice.
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Zhou, Lina, Godse, Sandip, Sinha, Namita, Kodidela, Sunitha, Singh, Udai, and Kumar, Santosh
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RITONAVIR , *ATAZANAVIR , *OXIDANT status , *HIV , *HIV infections , *MACROPHAGES , *DARUNAVIR - Abstract
Although antiretroviral therapy (ART) can suppress peripheral HIV, patients still suffer from neuroHIV due to insufficient levels of ART drugs in the brain. Hence, this study focuses on developing a poly lactic-co-glycolic acid (PLGA) nanoparticle-based ART drug delivery system for darunavir (DRV) using an intranasal route that can overcome the limitation of drug metabolic stability and blood–brain barrier (BBB) permeability. The physicochemical properties of PLGA-DRV were characterized. The results indicated that PLGA-DRV formulation inhibits HIV replication in U1 macrophages directly and in the presence of the BBB without inducing cytotoxicity. However, the PLGA-DRV did not inhibit HIV replication more than DRV alone. Notably, the total antioxidant capacity remained unchanged upon treatment with both DRV or PLGA-DRV in U1 cells. Compared to DRV alone, PLGA-DRV further decreased reactive oxygen species, suggesting a decrease in oxidative stress by the formulation. Oxidative stress is generally increased by HIV infection, leading to increased inflammation. Although the PLGA-DRV formulation did not further reduce the inflammatory response, the formulation did not provoke an inflammatory response in HIV-infected U1 macrophages. As expected, in vitro experiments showed higher DRV permeability by PLGA-DRV than DRV alone to U1 macrophages. Importantly, in vivo experiments, especially using intranasal administration of PLGA-DRV in wild-type mice, demonstrated a significant increase in the brain-to-plasma ratio of DRV compared to the free DRV. Overall, findings from this study attest to the potential of the PLGA-DRV nanoformulation in reducing HIV pathogenesis in macrophages and enhancing drug delivery to the brain, offering a promising avenue for treating HIV-related neurological disorders. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Resveratrol and its analogs suppress HIV replication, oxidative stress, and inflammation in macrophages.
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Kumar, Santosh, Sinha, Namita, Kodidela, Sunitha, Godse, Sandip, Singla, Bhupesh, Singh, Udai P., and Bhat, Hari K.
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RESVERATROL ,HIV infections ,MACROPHAGES ,ANTIRETROVIRAL agents ,OXIDATIVE stress - Abstract
HIV suppression in brain viral reservoirs, especially macrophages, and microglia is critical to suppress HIV neuropathogenesis and subsequently HIV-associated neurocognitive disorders (HAND). Since most antiretroviral therapy (ART) drugs do not achieve optimal therapeutic concentrations in the brain and can cause neurotoxicity, an alternative/adjuvant therapy is needed to suppress HIV neuropathogenesis. In this study, our objectives were to examine the anti-HIV, antioxidant, and anti-inflammatory potential of resveratrol (RES) and its synthetic analogs 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol} (TIMBD) and 4-(E)-{(4-hydroxyphenylimino)-methylbenzene,1,2-diol} (HPIMBD) in HIV-infected macrophages. We used HIV replication (viral load), oxidative stress (reactive oxygen species and antioxidant enzymes), and inflammatory response (pro- and anti-inflammatory cytokines/chemokines) assays to achieve the objectives of the study. Our results showed that RES and its analogs HPIMBD and TIMBD at 25 µM concentration significantly decrease HIV replication in both primary monocyte-derived macrophages and U1-differentiated macrophages. Moreover, RES and its analogs do not induce any cytotoxicity for up to 3 days in these cells. Further, treatment with RES and TIMBD (25 µM) also reduced the levels of reactive oxygen species without affecting the expression of antioxidant enzymes, SOD1, and catalase in U1 macrophages. Besides, RES and HPIMBD treatment inhibited the proinflammatory cytokines and chemokines in U1 macrophages, which was associated with decreased levels of anti-inflammatory cytokines. Importantly, our western blot experiments show that RES also decreases cellular proinflammatory cytokine IL-1β, which is usually elevated in both myeloid and neuronal cells upon HIV infection. Taken together, our results suggest that RES and/or its analogs are important adjuvants that may be used not only to suppress HIV but also oxidative stress and inflammation in brain viral reservoirs. [ABSTRACT FROM AUTHOR]
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- 2023
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6. Nanocarrier-mediated curcumin delivery: An adjuvant strategy for CNS disease treatment.
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Godse, Sandip, Zhou, Lina, Sakshi, Swarna, Singla, Bhupesh, Singh, Udai P, and Kumar, Santosh
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- 2023
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7. Targeted Drug Delivery to the Central Nervous System Using Extracellular Vesicles.
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Zhou, Lina, Kodidela, Sunitha, Godse, Sandip, Thomas-Gooch, Stacey, Kumar, Asit, Raji, Babatunde, Zhi, Kaining, Kochat, Harry, and Kumar, Santosh
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TARGETED drug delivery ,EXTRACELLULAR vesicles ,CENTRAL nervous system ,PERIPHERAL nervous system ,BLOOD-brain barrier ,DRUG development ,CENTRAL nervous system stimulants ,POISONS - Abstract
The blood brain barrier (BBB) maintains the homeostasis of the central nervous system (CNS) and protects the brain from toxic substances present in the circulating blood. However, the impermeability of the BBB to drugs is a hurdle for CNS drug development, which hinders the distribution of the most therapeutic molecules into the brain. Therefore, scientists have been striving to develop safe and effective technologies to advance drug penetration into the CNS with higher targeting properties and lower off-targeting side effects. This review will discuss the limitation of artificial nanomedicine in CNS drug delivery and the use of natural extracellular vesicles (EVs), as therapeutic vehicles to achieve targeted delivery to the CNS. Information on clinical trials regarding CNS targeted drug delivery using EVs is very limited. Thus, this review will also briefly highlight the recent clinical studies on targeted drug delivery in the peripheral nervous system to shed light on potential strategies for CNS drug delivery. Different technologies engaged in pre- and post-isolation have been implemented to further utilize and optimize the natural property of EVs. EVs from various sources have also been applied in the engineering of EVs for CNS targeted drug delivery in vitro and in vivo. Here, the future feasibility of those studies in clinic will be discussed. [ABSTRACT FROM AUTHOR]
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- 2022
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8. Nutraceuticals in HIV and COVID-19-Related Neurological Complications: Opportunity to Use Extracellular Vesicles as Drug Delivery Modality.
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Kodidela, Sunitha, Godse, Sandip, Kumar, Asit, Nguyen, Xuyen H., Cernasev, Alina, Zhou, Lina, Singh, Ajay Kumar, Bhat, Hari K., and Kumar, Santosh
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EXTRACELLULAR vesicles , *NEUROLOGIC manifestations of general diseases , *VIRUS diseases , *FUNCTIONAL foods , *COVID-19 , *POLYMERSOMES , *HIV infections - Abstract
Simple Summary: In this review, we discuss the potential use of extracellular vesicles (EVs) to deliver dietary supplements to the brain to reduce brain complications associated with HIV, COVID-19, and other brain disorders. Brain-related complications affect people with HIV and COVID-19 alike. Moreover, since HIV patients are at a higher risk of contracting COVID-19, their neurological problems can be exacerbated by COVID-19. The use of dietary supplements together with available treatment options has been shown to reduce the severity of infections. However, these treatments are not chemically compatible with the body's blood–brain barrier defense mechanism. Therefore, a viable delivery method is needed to deliver drugs and nutraceuticals to the brain in HIV and COVID-19 comorbid patients. People living with HIV/AIDS (PLWHA) are at an increased risk of severe and critical COVID-19 infection. There is a steady increase in neurological complications associated with COVID-19 infection, exacerbating HIV-associated neurocognitive disorders (HAND) in PLWHA. Nutraceuticals, such as phytochemicals from medicinal plants and dietary supplements, have been used as adjunct therapies for many disease conditions, including viral infections. Appropriate use of these adjunct therapies with antiviral proprieties may be beneficial in treating and/or prophylaxis of neurological complications associated with these co-infections. However, most of these nutraceuticals have poor bioavailability and cannot cross the blood–brain barrier (BBB). To overcome this challenge, extracellular vesicles (EVs), biological nanovesicles, can be used. Due to their intrinsic features of biocompatibility, stability, and their ability to cross BBB, as well as inherent homing capabilities, EVs hold immense promise for therapeutic drug delivery to the brain. Therefore, in this review, we summarize the potential role of different nutraceuticals in reducing HIV- and COVID-19-associated neurological complications and the use of EVs as nutraceutical/drug delivery vehicles to treat HIV, COVID-19, and other brain disorders. [ABSTRACT FROM AUTHOR]
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- 2022
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9. Effect of myricetin on blood pressure and metabolic alterations in fructose hypertensive rats.
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Godse, Sandip, Mohan, Mahalaxmi, Kasture, Veena, and Kasture, Sanjay
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BLOOD pressure , *FRUCTOSE , *INSULIN , *HYPERTRIGLYCERIDEMIA , *CATECHOLAMINES , *ANTIHYPERTENSIVE agents - Abstract
Fructose feeding induces a rise in blood pressure in normal rats and is associated with insulin resistance, hyperinsulinemia, and hypertriglyceridemia. We have examined the effect of myricetin (100 and 300 mg/kg, p.o. for 6 weeks) isolated from Vitis vinifera Linn. (Vitaceae) on systolic blood pressure (SBP), vascular reactivity, serum glucose, triglycerides, cholesterol, and insulin in fructose-induced hypertension. Myricetin reduced systolic blood pressure and vascular reactivity changes to catecholamines and reversed the metabolic alterations induced by fructose. The cumulative concentration–response curve (CCRC) of Ang II was shifted toward the right in rats treated with myricetin, using isolated strips of ascending colon. The results suggest that myricetin could prevent the development of high blood pressure induced by a diet rich in fructose, probably by reversing the metabolic alterations induced by fructose. In conclusion, myricetin has antihypertensive action in the fructose model. [ABSTRACT FROM AUTHOR]
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- 2010
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10. Curcumin enhances elvitegravir concentration and alleviates oxidative stress and inflammatory response.
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Godse S, Zhou L, Sinha N, Kodidela S, Kumar A, Singh UP, and Kumar S
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In this study, we investigated the potential of using curcumin (CUR) as an adjuvant to enhance the delivery of antiretroviral drug elvitegravir (EVG) across the BBB, and alleviate oxidative stress and inflammatory response, which are the major hallmark of HIV neuropathogenesis. In a mouse model, we compared the biodistribution of EVG alone and in combination with CUR using intraperitoneal (IP) and intranasal (IN) routes. IN administration showed a significantly higher accumulation of EVG in the brain, while both IP and IN routes led to increased EVG levels in the lungs and liver. The addition of CUR further enhanced EVG brain delivery, especially when administered via the IN route. The expression of neural marker proteins, synaptophysin, L1CAM, NeuN, and GFAP was not significantly altered by EVG or CUR alone or their combination, indicating preserved neural homeostasis. After establishing improved brain concentration and safety of CUR-adjuvanted EVG in mice in acute treatment, we studied the effect of this treatment in HIV-infected U1 macrophages. In U1 macrophages, we also observed that the addition of CUR enhanced the intracellular concentration of EVG. The total area under the curve (AUC
tot ) for EVG was significantly higher in the presence of CUR. We also evaluated the effects of CUR on oxidative stress and antioxidant capacity in EVG-treated U1 macrophages. CUR reduced oxidative stress, as evidenced by decreased reactive oxygen species (ROS) levels and elevated antioxidant enzyme expression. Furthermore, the combination of CUR and EVG exhibited a significant reduction in proinflammatory cytokines (TNFα, IL-1β, IL-18) and chemokines (RANTES, MCP-1) in U1 macrophages. Additionally, western blot analysis confirmed the decreased expression of IL-1β and TNF-α in EVG + CUR-treated cells. These findings suggest the potential of CUR to enhance EVG permeability to the brain and subsequent efficacy of EVG, including HIV neuropathogenesis.- Published
- 2023
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11. Intranasal delivery of darunavir improves brain drug concentrations in mice for effective HIV treatment.
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Kumar A, Zhou L, Godse S, Sinha N, Ma D, Parmar K, and Kumar S
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Despite the availability of combined antiretroviral therapy (cART), which reduces the HIV replication in chronically HIV-infected patients, HIV associated neurocognitive disorders (HAND) persists in the brain. The blood-brain barrier (BBB) is the major barrier for the penetration of drugs including antiretrovirals, limiting the drug penetration to the brain. In the present study, we have shown improved brain drug concentration in mice for darunavir (DRV), an FDA-approved drug, using an intranasal (IN) delivery method that bypasses the BBB. Here, we compared the time-dependent biodistribution of DRV at two different concentrations, high (25 mg/kg) and low (2.5 mg/kg), using two administration routes intravenous (IV) and intranasal (IN) in brain, liver, lungs, and plasma. Compared with IV administration, IN administration demonstrated a significantly improved DRV penetration in the brain at both low and high DRV concentrations (IV vs IN: at 2.5 mg/kg: 6.91 ± 1.69 ng/g vs 12.08 ± 2.91 ng/g, at 25 mg/kg: 12.84 ± 2.88 ng/g vs 19.74 ± 1.80 ng/g). As expected, IN administration showed significantly lower DRV concentrations in plasma (IV vs IN: at 2.5 mg/kg: 81.37 ± 22.04 ng/g vs 19.91 ± 12.65 ng/g, at 25 mg/kg: 899.12 ± 136.93 ng/g vs 320.56 ± 40.04 ng/g) and liver (IV vs IN: at 2.5 mg/kg: 118.39 ± 28.13 ng/g vs 29.27 ± 4.17 ng/g at 25 mg/kg: 1085.18 ± 255.0 ng/g vs 833.83 ± 242.4 ng/g). The IN administration did not show significant change in lungs compared to the IV administration. As a result, these findings suggest that the IN route can increase the DRV level in the brain, suppressing HIV in the brain reservoirs. Additionally, it could also reduce off-target effects, especially in peripheral organs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)
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- 2022
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