A new nanomedicine based on didanosine glycerolipidic prodrug enhances the long term accumulation of drug in a HIV sanctuary

Skanji, Rym; Andrieux, Karine; Lalanne, Muriel; Caron, Joachim; Bourgaux, Claudie; Degrouard, Jéril; Brisset, François; Gueutin, Claire; Chacun, Hélène; Dereuddre‐Bosquet, Nathalie; Paci, Angélo; Vassal, Gilles; Bauduin, Laurent; Garcia‐Argote, Sébastien; Rousseau, Bernard; Clayette, Pascal; Desmaële, Didier; Couvreur, Patrick

doi:10.1016/j.ijpharm.2011.05.005

Cited by 17 publications

(8 citation statements)

References 28 publications

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“…In conclusion, the data showed preservation of Ddi encapsulated in the liposomes with enhanced antiviral activity, blood half-life, and intestinal accumulation. 77 As mentioned previously, the therapeutic efficacy of a drug administered by the oral route strongly depends on the administered dose, GIT absorption, and its bioavailability. To improve the oral bioavailability of Efv in another recent study, the drug was encapsulated within poly-ε-caprolactone PVA NPs (~250 nm).…”

Section: Infectious and Parasitic Diseasesmentioning

confidence: 97%

Nanodelivery systems and stabilized solid-drug nanoparticles for orally administered medicine: current landscape

Kermanizadeh¹,

Powell²,

Stone³

2018

IJN

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The use of nanoparticles as a means of targeted delivery of therapeutics and imaging agents could greatly enhance the transport of biologically active contents to specific target tissues, while avoiding or reducing potentially undesired side effects. Generally speaking, the oral route of administration is associated with good patient compliance, as it is convenient, economical, noninvasive, and does not require special training. Here, we review the progress of the utilization of nanodelivery-system carriers or stabilized solid-drug nanoparticles following oral administration, with particular attention on toxicological data. Mechanisms of cytotoxicity are discussed and the problem of extrapolating knowledge to human scenarios highlighted. Additionally, issues associated with administration of drugs via the oral route are underlined, while strategies utilized to overcome these are highlighted. This review aims to offer a balanced overview of strategies currently being used in the application of nanosize constructs for oral medical applications.

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Section: Infectious and Parasitic Diseasesmentioning

confidence: 97%

Nanodelivery systems and stabilized solid-drug nanoparticles for orally administered medicine: current landscape

Kermanizadeh¹,

Powell²,

Stone³

2018

IJN

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“…The principal focus has been to increase the hydrophobic-lipophilic character of the hydrophilic NRTIs to increase tissue penetration and apparent plasma half-life. Skanji et al developed a glycerolipidic prodrug of didanosine that was incorporated into an orally administered liposomal delivery system, and showed significant delivery of the drug to viral reservoirs including testes, gut, and bone marrow [ 115 ]. Hillaireau et al furthered these findings by developing squalenated didanosine and dideoxycytidine prodrug nanoassemblies that were stabilized with PEG and reported significant drug delivery to viral reservoirs [ 100 ].…”

Section: The Use Of Prodrugs For Infectious Diseasesmentioning

confidence: 99%

Prodrug Therapies for Infectious and Neurodegenerative Diseases

et al. 2022

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Prodrugs are bioreversible drug derivatives which are metabolized into a pharmacologically active drug following chemical or enzymatic modification. This approach is designed to overcome several obstacles that are faced by the parent drug in physiological conditions that include rapid drug metabolism, poor solubility, permeability, and suboptimal pharmacokinetic and pharmacodynamic profiles. These suboptimal physicochemical features can lead to rapid drug elimination, systemic toxicities, and limited drug-targeting to disease-affected tissue. Improving upon these properties can be accomplished by a prodrug design that includes the careful choosing of the promoiety, the linker, the prodrug synthesis, and targeting decorations. We now provide an overview of recent developments and applications of prodrugs for treating neurodegenerative, inflammatory, and infectious diseases. Disease interplay reflects that microbial infections and consequent inflammation affects neurodegenerative diseases and vice versa, independent of aging. Given the high prevalence, personal, social, and economic burden of both infectious and neurodegenerative disorders, therapeutic improvements are immediately needed. Prodrugs are an important, and might be said a critical tool, in providing an avenue for effective drug therapy.

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“…The ability of lipid nanocarriers to mediate the ARV distribution and increase their half-lives is therefore an important advantage. For example, liposomes have been documented as capable to increase half-lives of d4T, AZT, ddI, and RTV [ 13 , 14 , 15 , 16 , 20 , 79 , 80 ] ( Table 3 ). Finally, many ARTs have a limited bioavailability in the brain, but the ability of lipid nanocarriers to mediate the brain delivery of ARVs has been widely documented, either for liposomes that potentially improve brain accumulation of AZT [ 81 ], or for SLN used for improving brain bioavailability of ATV, SQV, EFV, NVP and DRV [ 64 , 65 , 82 , 83 , 84 , 85 ], or NLC used as carriers of LPV, ATV, ETR [ 83 , 86 , 87 ] and NE improving brain accumulation of SQV and IDV [ 88 , 89 , 90 ].…”

Section: Lipid-based Nanocarriers For Delivery Of Arv Agentsmentioning

confidence: 99%

Lipid Nanocarriers for Anti-HIV Therapeutics: A Focus on Physicochemical Properties and Biotechnological Advances

et al. 2021

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Since HIV was first identified, and in a relatively short period of time, AIDS has become one of the most devastating infectious diseases of the 21st century. Classical antiretroviral therapies were a major step forward in disease treatment options, significantly improving the survival rates of HIV-infected individuals. Even though these therapies have greatly improved HIV clinical outcomes, antiretrovirals (ARV) feature biopharmaceutic and pharmacokinetic problems such as poor aqueous solubility, short half-life, and poor penetration into HIV reservoir sites, which contribute to the suboptimal efficacy of these regimens. To overcome some of these issues, novel nanotechnology-based strategies for ARV delivery towards HIV viral reservoirs have been proposed. The current review is focused on the benefits of using lipid-based nanocarriers for tuning the physicochemical properties of ARV to overcome biological barriers upon administration. Furthermore, a correlation between these properties and the potential therapeutic outcomes has been established. Biotechnological advancements using lipid nanocarriers for RNA interference (RNAi) delivery for the treatment of HIV infections were also discussed.

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A new nanomedicine based on didanosine glycerolipidic prodrug enhances the long term accumulation of drug in a HIV sanctuary

Cited by 17 publications

References 28 publications

Nanodelivery systems and stabilized solid-drug nanoparticles for orally administered medicine: current landscape

Nanodelivery systems and stabilized solid-drug nanoparticles for orally administered medicine: current landscape

Prodrug Therapies for Infectious and Neurodegenerative Diseases

Lipid Nanocarriers for Anti-HIV Therapeutics: A Focus on Physicochemical Properties and Biotechnological Advances

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