Development and characterization of biodegradable nanospheres as delivery systems of anti-ischemic adenosine derivatives

Dalpiaz, Alessandro; Leo, Eliana Grazia; Vitali, Federica; Pavan, Barbara; Scatturin, Angelo; Bortolotti, Fabrizio; Manfredini, Stefano; Durini, Elisa; Forni, Flavio; Brina, Barbara; Vandelli, Maria Angela

doi:10.1016/j.biomaterials.2004.04.033

Cited by 22 publications

(13 citation statements)

References 30 publications

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“…This value was not significantly different from the half-life value of UDCA-AZT alone indicating that the presence of the coating of Pluronic on NPs does not change the half-life value of the prodrug. These data are in good agreement with those obtained by previous pharmacokinetic studies of different drugs and prodrugs in the presence of unloaded PLA, PLGA or solid lipid micro and NPs (Dalpiaz et al, 2001(Dalpiaz et al, , 2002(Dalpiaz et al, , 2005(Dalpiaz et al, , 2008(Dalpiaz et al, , 2009(Dalpiaz et al, , 2010Leo et al, 2006a,b). The amounts of AZT and UDCA-AZT detected after 30 min of incubation of the free or encapsulated prodrug in rat liver homogenates are reported in Figure 6.…”

Section: Hydrolysis Studies Of Free and Encapsulated Udcaàazt In Rat supporting

confidence: 82%

“…We have therefore demonstrated that the lipophilic prodrug 5 0 -octanoyl-CPA (Dalpiaz et al, 2001) can be encapsulated in PLA NP and be able to control its release. These satisfactory results were obtained by the nanoprecipitation technique (Dalpiaz et al, 2005;Leo et al, 2006a). It is important to remark that CPA is an adenosine derivative, whereas AZT is a timidine derivative.…”

Section: In Vitro N 6 -Cyclopentyladenosine Release Studies From Npsmentioning

confidence: 64%

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Development and characterization of PLGA nanoparticles as delivery systems of a prodrug of zidovudine obtained by its conjugation with ursodeoxycholic acid

Dalpiaz¹,

Contado²,

Mari³

et al. 2013

Drug Delivery

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Materials and methods:The mean diameter of the NP prepared by nanoprecipitation or emulsion/solvent evaporation methods was determined using both photon correlation spectroscopy and sedimentation field-flow fractionation; particle morphology was detected by scanning electron microscope. The stability of the free and encapsulated UDCA-AZT was evaluated in rat liver homogenates by high-performance liquid chromatography analysis. Results and discussion: The mean diameter of the NPs was found to be $600 nm with a relatively high polydispersity. The NPs obtained by emulsion/solvent evaporation were not able to control the prodrug release, differently from NPs obtained by nanoprecipitation. The presence of the Pluronic coating did not substantially modify the kinetics of the drug release, or the extent of the burst effect that were instead only influenced by the preparation parameters. UDCA-AZT incorporated in the NPs was more stable in the rat liver homogenates than the free prodrug and no influence of the Pluronic coating was observed. Conclusions: Considering the different potential applications of nanoparticles coated and uncoated with Pluronic (brain and macrophage targeting, respectively), both of these nanoparticle systems could be useful in the therapies against HIV.

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Section: Hydrolysis Studies Of Free and Encapsulated Udcaàazt In Rat supporting

confidence: 82%

Section: In Vitro N 6 -Cyclopentyladenosine Release Studies From Npsmentioning

confidence: 64%

Development and characterization of PLGA nanoparticles as delivery systems of a prodrug of zidovudine obtained by its conjugation with ursodeoxycholic acid

Dalpiaz¹,

Contado²,

Mari³

et al. 2013

Drug Delivery

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“…A systemic use of A 1 receptor agonists has long been precluded because of the occurrence of peripheral side effects. However, innovative delivery systems are now available that may allow a systemic use of A 1 receptor agonists in neurodegenerative disorders (Dalpiaz et al, 2005). …”

Section: A 1 and Mglu3 Receptor Antiapoptotic Effect In Astrocytes 1377mentioning

confidence: 99%

Molecular Signalling Mediating the Protective Effect of A₁Adenosine and mGlu3 Metabotropic Glutamate Receptor Activation against Apoptosis by Oxygen/Glucose Deprivation in Cultured Astrocytes

Ciccarelli¹,

D’Alimonte²,

Ballerini³

et al. 2007

Mol Pharmacol

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Astrocyte death may occur in neurodegenerative disorders and complicates the outcome of brain ischemia, a condition associated with high extracellular levels of adenosine and glutamate. We show that pharmacological activation of A 1 adenosine and mGlu3 metabotropic glutamate receptors with N 6 -chlorocyclopentyladenosine (CCPA) and (Ϫ)2-oxa-4-aminocyclo-[3.1.0]hexane-4,6-dicarboxylic acid (LY379268), respectively, protects cultured astrocytes against apoptosis induced by a 3-h exposure to oxygen/glucose deprivation (OGD). Protection by CCPA and LY379268 was less than additive and was abrogated by receptor blockade with selective competitive antagonists or pertussis toxin. Both in control astrocytes and in astrocytes exposed to OGD, CCPA and LY379268 induced a rapid activation of the phosphatidylinositol-3-kinase (PI3K) and extracellular signal-regulated kinases 1 and 2 (ERK1/2)/mitogen-activated protein kinase (MAPK) pathways, which are known to support cell survival. In cultures exposed to OGD, CCPA and LY379268 reduced the activation of c-Jun N-terminal kinase and p38/MAPK, reduced the levels of the proapoptotic protein Bad, increased the levels of the antiapoptotic protein Bcl-X L , and were highly protective against apoptotic death, as shown by nuclear 4Ј-6-diamidino-2-phenylindole staining and measurements of caspase-3 activity. All of these effects were attenuated by treatment with 1,4-diamino-2,3-dicyano-1,4-bis(methylthio)butadiene (U0126) and 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002), which inhibit the MAPK and the PI3K pathways, respectively. These data suggest that pharmacological activation of A 1 and mGlu3 receptors protects astrocytes against hypoxic/ischemic damage by stimulating the PI3K and ERK1/2 MAPK pathways.Astrocytes, the most abundant glial cell types in the brain, provide metabolic and trophic support to neurons by several mechanisms that include the clearance of ions and environmental toxins, the supply of energy substrates, and the production of trophic factors, and modulate synaptic activity (Volterra and Meldolesi, 2005). Impairments in these functions critically affect neuronal survival.Recent studies have shown that ischemic and inflammatory insults induce astrocyte apoptotic death, and this contributes to the pathophysiology of short-and long-term neurodegenerative disorders (Takuma et al., 2004). Apoptotic astrocytes are found in Alzheimer's disease (Kobayashi et al., ABBREVIATIONS: CCPA, N 6 -chlorocyclopentyladenosine; ASK1, apoptosis-signal-regulating kinase 1; DAPI, 4Ј-6-diamidino-2-phenylindole; DMEM, Dulbecco's modified Eagle's medium; DPCPX, 1,3-dipropyl-8-cyclopentyl xanthine; ERK1/2, extracellular signal-regulated kinases 1 and 2; HRP, horseradish peroxidase; JNK, c-Jun N-terminal kinase; LY294002, 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride; LY341495, (2S,1ЈS,2ЈS)-2(9-xanthylmethyl)-2-(2Ј-carboxycyclo-propyl)glycine; LY379268, (Ϫ)2-oxa-4-aminocyclo-[3.1.0] hexane-4,6-dicarboxylic acid; MAPK, mitogen-activated p...

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“…In the follow up study, Dalpiaz et al (Dalpiaz et al, 2005) reported biodegradable PLA nanospheres as delivery systems for CPA and its pro-drug 5’-octanoyl-CPA (Oct-CPA). The PLA nanospheres were fabricated by double emulsion solvent evaporation method or nanoprecipitation, and the nanoparticles were collected by ultracentrifugagtion, gel filtration or through dialysis.…”

Section: Particle-based Adenosine Carriersmentioning

confidence: 99%

Adenosine-associated delivery systems

Kazemzadeh-Narbat¹,

Annabi²,

Tamayol³

et al. 2015

Journal of Drug Targeting

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Adenosine is a naturally occurring purine nucleoside in every cell. Many critical treatments such as modulating irregular heartbeat (arrhythmias), regulation of central nervous system (CNS) activity, and inhibiting seizural episodes can be carried out using adenosine. Despite the significant potential therapeutic impact of adenosine and its derivatives, the severe side effects caused by their systemic administration have significantly limited their clinical use. In addition, due to adenosine’s extremely short half-life in human blood (less than 10 s), there is an unmet need for sustained delivery systems to enhance efficacy and reduce side effects. In this paper, various adenosine delivery techniques, including encapsulation into biodegradable polymers, cell-based delivery, implantable biomaterials, and mechanical-based delivery systems, are critically reviewed and the existing challenges are highlighted.

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Development and characterization of biodegradable nanospheres as delivery systems of anti-ischemic adenosine derivatives

Cited by 22 publications

References 30 publications

Development and characterization of PLGA nanoparticles as delivery systems of a prodrug of zidovudine obtained by its conjugation with ursodeoxycholic acid

Development and characterization of PLGA nanoparticles as delivery systems of a prodrug of zidovudine obtained by its conjugation with ursodeoxycholic acid

Molecular Signalling Mediating the Protective Effect of A₁Adenosine and mGlu3 Metabotropic Glutamate Receptor Activation against Apoptosis by Oxygen/Glucose Deprivation in Cultured Astrocytes

Adenosine-associated delivery systems

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Development and characterization of biodegradable nanospheres as delivery systems of anti-ischemic adenosine derivatives

Cited by 22 publications

References 30 publications

Development and characterization of PLGA nanoparticles as delivery systems of a prodrug of zidovudine obtained by its conjugation with ursodeoxycholic acid

Development and characterization of PLGA nanoparticles as delivery systems of a prodrug of zidovudine obtained by its conjugation with ursodeoxycholic acid

Molecular Signalling Mediating the Protective Effect of A1Adenosine and mGlu3 Metabotropic Glutamate Receptor Activation against Apoptosis by Oxygen/Glucose Deprivation in Cultured Astrocytes

Adenosine-associated delivery systems

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Molecular Signalling Mediating the Protective Effect of A₁Adenosine and mGlu3 Metabotropic Glutamate Receptor Activation against Apoptosis by Oxygen/Glucose Deprivation in Cultured Astrocytes