Interaction of acyclovir and its squalenoyl–acyclovir prodrug with DMPC in monolayers at the air/water interface

Sarpietro, Maria Grazia; Rocco, Flavio; Micieli, Dorotea; Ottimo, Sara; Ceruti, Maurizio; Castelli, Francesco

doi:10.1016/j.ijpharm.2010.05.035

Cited by 20 publications

(10 citation statements)

References 21 publications

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“…Langmuir monolayers are also usually used for investigating amphiphilicity and possible interaction between amphiphiles [8,9]. Some important information about the molecular configurations of amphiphiles can be predicated according to their monolayer behavior.…”

Section: Introductionmentioning

confidence: 99%

Rational design of didodecyldimethylammonium bromide-based nanoassemblies for gene delivery

Jin

Wang

et al. 2015

Colloids and Surfaces B: Biointerfaces

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Section: Introductionmentioning

confidence: 99%

Rational design of didodecyldimethylammonium bromide-based nanoassemblies for gene delivery

Jin

Wang

et al. 2015

Colloids and Surfaces B: Biointerfaces

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“…It is well known that esterases are present in several ocular structures, and their activity is the main factor responsible for the bioreversion of amino acid prodrugs of acyclovir [19], [39] and [42]. Our study employed a lipophilic prodrug of ACV, obtained by conjugation with 1,1′,2-trisnorsqualenoic acid, as has been proposed by Sarpietro et al [33] and [43]. In particular, Sarpietro et al highlighted the fact that the formation of a lipophilic prodrug gives rise to a stronger interaction with the biomembrane model and is absorbed in larger quantities by the biomembrane model constituted by dimyristoylphosphatidylcholine, than 1,1′,2-trisnorsqualenoic acid [33] and [43].…”

Section: Discussionmentioning

confidence: 94%

“…Our study employed a lipophilic prodrug of ACV, obtained by conjugation with 1,1′,2-trisnorsqualenoic acid, as has been proposed by Sarpietro et al [33] and [43]. In particular, Sarpietro et al highlighted the fact that the formation of a lipophilic prodrug gives rise to a stronger interaction with the biomembrane model and is absorbed in larger quantities by the biomembrane model constituted by dimyristoylphosphatidylcholine, than 1,1′,2-trisnorsqualenoic acid [33] and [43]. The results reported by Sarpietro et al using differential scanning calorimetry (DSC) analysis [33] indicated that 1,1′,2-trisnorsqualenoic acid and SQACV had a fluidizing effect on the phospholipid bilayer, interacting with the hydrophobic acyl chains, while acyclovir does not enter the phospholipid bilayers [44].…”

Section: Discussionmentioning

confidence: 99%

Nonpolymeric nanoassemblies for ocular administration of acyclovir: Pharmacokinetic evaluation in rabbits

Stella

Berlier

Rocco

et al. 2012

European Journal of Pharmaceutics and Biopharmaceutics

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The aim of this study was to increase bioavailability of the antiviral drug acyclovir (ACV) when administered by the ocular route. For this purpose, a new lipophilic derivative of acyclovir was synthesized, both possessing greater lipophilicity and providing the formation of a homogeneous water dispersion with higher amount of ACV than the aqueous solution of the parent drug. This was done by chemically linking acyclovir to the isoprenoid chain of squalene, obtaining 4′-trisnorsqualenoylacyclovir (SQACV), in which squalene is covalently coupled to the 4′-hydroxy group of acyclovir. This new prodrug was then formulated as nonpolymeric nanoassemblies through nanoprecipitation; the resulting particles were characterized in terms of mean diameter, zeta potential, and stability. The pharmacokinetic profile of the prodrug in the tear fluid and in the aqueous humor of rabbits was evaluated and compared to that of the parent drug. Data showed that SQACV nanoassemblies increased the amount of ACV in the aqueous humor of rabbits compared to free ACV solution. This new amphiphilic prodrug of acyclovir is a very promising tool to increase the ocular bioavailability of the parent drug.

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“…The squalenoylation technology was also extended to develop a new ester prodrug with antiviral activity, squalenoyl-acyclovir (Sq-ACV). The interaction of Sq-ACV with biomembrane models made of DMPC MLV was studied by means of DSC and LB techniques [62,63]. The DSC study concerned the effects of ACV and of Sq-ACV towards the liposomal biomembranes (MLV) [62].…”

Section: ) Squalene-derived Nanoparticlesmentioning

confidence: 99%

Recent studies on the delivery of hydrophilic drugs in nanoparticulate systems

Berlier

Battaglia

Brusa

et al. 2016

Journal of Drug Delivery Science and Technology

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This review discusses some approaches developed by the Turin University Pharmaceutical Technology group to enhance the entrapment efficiency of mainly hydrophilic molecules within nanoparticulate systems, and to optimize their delivery. Many attempts have been made to increase, either passively or actively, the delivery of hydrophilic drugs. One approach consists of their association to liposomes, in some cases by developing lipophilic prodrugs of anticancer hydrophilic molecules, and encapsulating them in liposomes; in some cases these are then further conjugated with suitable vectors, to increase targeting efficiency. The transformation of hydrophilic drugs into lipophilic prodrugs can also overcome problems of poor entrapment efficiency, and the frequentlyobserved rapid release from polymer nanocarriers, for example nanospheres or nanocapsules obtained from various PEGylated poly(alkylcyanoacrylate) copolymers. Strategies have also been developed to enhance hydrophilic drug entrapment in solid lipid nanoparticles (SLN). Of these, hydrophobic ion pairing (HIP) was designed to enable various antitumor drugs to be entrapped in SLN produced by the coacervation method. The w/o/w emulsion solvent dilution technique may also be employed to entrap peptide drugs, such as insulin, directly in the inner aqueous phase. Another strategy entails covalent linkage of antitumoral and antiviral drugs to a squalenoyl-derived chain; this produces bioconjugates that spontaneously self-assemble in an aqueous medium as stable nanoparticles. Another development comprises mesoporous silica nanoparticles with immobilized hydrophilic antioxidants, for topical applications. Ordered mesoporous silica (MCM-41) nanoparticles were complexed with hydrophilic antioxidants (Trolox ® or rutin) employing different inclusion procedures, varying solvent and pretreatment of the silica matrix; on exposure to UV illumination, mesoporous silica significantly improved stability over time. Finally, polymer-shelled and perfluoropentane-cored nanobubbles have been designed as versatile multifunctional carriers for the delivery of gases, drugs and genes; the size range is below 500 nm, with shell thickness in the 30-50 nm range.(lectins), or macromolecular conjugates to tumor tissues. Further, collaboration with several European research groups lead to the development of particulate delivery systems (liposomes, polymer nanoparticles) and, more recently, to the squalenoylation platform. Colloidal systems, such as liposomes, nanoparticles, and microemulsions, have mainly been reported in the literature for use as carriers of hydrophobic drugs. Delivery of hydrophilic molecules is a challenging goal, which requires multidisciplinary approaches. This review essentially focused on the various strategies that may be employed to deliver hydrophilic active substances. Many drugs are hydrophilic, and many of these are low-molecular weight molecules (less than 500 Da). According to the United States Pharmacopeia (USP), hydrophilic drugs are classified in the range ve...

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Interaction of acyclovir and its squalenoyl–acyclovir prodrug with DMPC in monolayers at the air/water interface

Cited by 20 publications

References 21 publications

Rational design of didodecyldimethylammonium bromide-based nanoassemblies for gene delivery

Rational design of didodecyldimethylammonium bromide-based nanoassemblies for gene delivery

Nonpolymeric nanoassemblies for ocular administration of acyclovir: Pharmacokinetic evaluation in rabbits

Recent studies on the delivery of hydrophilic drugs in nanoparticulate systems

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