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Cyclodextrin-based nanosponges (NS) are solid nanoparticles, obtained from the cross-linking of cyclodextrins that have been proposed as delivery systems for many types of drugs. Various NS derivatives are currently under investigation in order that their properties might be tuned for different applications. In this work, new carboxylated cyclodextrin-based nanosponges (Carb-NS) carrying carboxylic groups within their structure were purposely designed as novel Acyclovir carriers. TEM measurements revealed their spherical shape and size of about 400 nm. The behaviour of Carb-NS, with respect to the incorporation and delivery of Acyclovir, was compared to that of NS, previously investigated as a drug carrier. DSC, XRPD and FTIR analyses were used to investigate the two NS formulations. The results confirm the incorporation of the drug into the NS structure and NS-Acyclovir interactions. The Acyclovir loading into Carb-NS was higher than that obtained using NS, reaching about 70% (w/w). In vitro release studies showed the release kinetics of Acyclovir from Carb-NS to be prolonged in comparison with those observed with NS, with no initial burst effect. The NS uptake into cells was evaluated using fluorescent Carb-NS and revealed the nanoparticle internalisation. Enhanced antiviral activity against a clinical isolate of HSV-1 was obtained using Acyclovir loaded in Carb-NS., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The activity of antivirals can be enhanced by their incorporation in nanoparticulate delivery systems. Peculiar polymeric nanoparticles, based on a β-cyclodextrin-poly(4-acryloylmorpholine) monoconjugate (β-CD-PACM), are proposed as acyclovir carriers. The experimental procedure necessary to obtain the acyclovir-loaded nanoparticles using the solvent displacement preparation method will be described in this chapter. Fluorescent labeled nanoparticles are prepared using the same method for cellular trafficking studies. The biocompatibility assays necessary to obtain safe nanoparticles are reported. Section 4 of this chapter describes the assessment of the antiviral activity of the acyclovir-loaded nanoparticles., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Novel polymeric nanoparticles based on a beta-cyclodextrin-poly(4-acryloylmorpholine) mono-conjugate (beta-CD-PACM), a tadpole-shaped polymer in which the beta-CD ring is the hydrophilic head and the PACM chain the amphiphilic tail, were prepared by the solvent injection technique. Acyclovir-loaded nanoparticles were prepared from inclusion complexes of Acyclovir with beta-CD-PACM. Both unloaded and drug-loaded nanoparticles were characterized in terms of particle size distribution, morphology, zeta potential, drug loading and in vitro drug release rate. The antiviral activity of Acyclovir loaded into beta-CD-PACM nanoparticles against two clinical isolates of HSV-1 was evaluated and found to be remarkably superior compared with that of both the free drug and a soluble beta-CD-PACM complex reported in a previous paper. Fluorescent nanoparticles loaded with coumarin 6 were also prepared in order to investigate the nanoparticle cell uptake by confocal laser microscopy. It was found that the nanoparticles are internalized in cells and locate in the perinuclear compartment.

A poly(amidoamine) (PAA) copolymer with beta-cyclodextrin was obtained by polyaddition reaction of 6-deoxy-6-amino-beta-cyclodextrin (beta-CD-NH(2)) and 2-methylpiperazine to 2,2-bis(acrylamido)acetic acid in aqueous medium. This beta-CD/PAA copolymer bears beta-CD units along the macromolecular chain, is water-soluble and non-cytotoxic. The complexing capacity of beta-CD/PAA was determined using an antiviral drug, Acyclovir, as a model of poorly water-soluble drug. Complex formation was confirmed by means of DSC and FTIR analyses. beta-CD/PAA can solubilize up to 11% w/w of Acyclovir notably increasing the aqueous solubility of the drug. The in vitro release studies showed the dependence of Acyclovir release rate on the solution pH. The antiviral activity of Acyclovir beta-CD/PAA complex was evaluated against herpes simplex virus type I in cell cultures. The Acyclovir beta-CD/PAA complex exhibited a higher antiviral activity than the free drug.

Acyclovir is not a good candidate for passive permeation since its polarity and solubility limit is partitioning into the stratum corneum. This work aims to develop a new topical formulation for the acyclovir delivery. New chitosan nanospheres (NS) were prepared by a modified nano-emulsion template method. Chitosan NS were characterized by Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM), and an in vitro release study. The in vitro skin permeation experiment was carried out using Franz cells and was equipped with porcine skin. Biological studies were performed on the Vero cell line infected by HSV-1 and HSV-2 strains. The acyclovir loaded chitosan NS appeared with a spherical shape, a size of about 200 nm, and a negative zeta potential of about 40.0 mV. The loading capacity of the drug was about 8.5%. In vitro release demonstrated that the percentage of acyclovir delivered from the nanospheres was approximately 30% after six hours. The in vitro skin permeation studies confirmed an improved amount of permeated acyclovir. The acyclovir-NS complex displayed a higher antiviral activity than that of free acyclovir against both the HSV-1 and the HSV-2 strain. The acyclovir-loaded NS showed no anti-proliferative activity and no signs of cytotoxicity induced by NS was detected. Confocal laser scanning microscopy confirmed that the NS are taken up by the cells. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Vachellia (Acacia) nilotica and other plants of this genus have been used in traditional medicine of Asian and African countries to treat many disorders, including sexually transmitted diseases, but few studies were performed to validate their anti-microbial and anti-viral activity against sexually transmitted infections. Aim of the study The present study was undertaken to explore whether the ethnomedical use of V.nilotica to treat genital lesions is substantiated by its antiviral activity against the human immunodeficiency virus (HIV), the herpes simplex virus (HSV) and the human papillomavirus (HPV). Materials and methods The antiviral activity of V.nilotica was tested in vitro by virus-specific inhibition assays using HSV-2 strains, sensible or resistant to acyclovir, HIV-1IIIb strain and HPV-16 pseudovirion (PsV). The potential mode of action of extract against HSV-2 and HPV-16 was further investigated by virus inactivation and time-of-addition assays on cell cultures. Results V.nilotica chloroform, methanolic and water bark extracts exerted antiviral activity against HSV-2 and HPV-16 PsV infections; among these, methanolic extract showed the best EC50s with values of 4.71 and 1.80 µg/ml against HSV-2 and HPV-16, respectively, and it was also active against an acyclovir-resistant HSV-2 strain with an EC50 of 6.71 µg/ml. By contrast, no suppression of HIV infection was observed. Investigation of the mechanism of action revealed that the methanolic extract directly inactivated the infectivity of the HPV-16 particles, whereas a partial virus inactivation and interference with virus attachment (EC50 of 2.74 µg/ml) were both found to contribute to the anti-HSV-2 activity. Conclusions These results support the traditional use of V.nilotica applied externally for the treatment of genital lesions. Further work remains to be done in order to identify the bioactive components. [ABSTRACT FROM AUTHOR]

• Next generation platform of nanodroplets with a hybrid chitosan/cyclodextrin shell. • Chitosan nanodroplets with mucoadhesion and penetration enhancement properties. • Acyclovir loaded in nanodroplets showed enhanced antiviral activity against HSV-2. • Future nanomicrobicide for the local treatment of herpetic genital infections. Acyclovir is the gold standard drug for herpes simplex virus type 2 (HSV-2) infection treatment. Vaginal topical therapy with acyclovir is hampered due to its poor bioavailability, low retention at the vaginal mucosa, thus requiring high doses and frequent administrations. Nanocarriers have been proposed to overcome the challenges associated with antiviral delivery. This work aims at developing a novel formulation consisting of sulfobutyl ether-β-cyclodextrin decorated nanodroplets for acyclovir topical delivery to improve its antiviral effectiveness. To obtain acyclovir-loaded nanodroplets, the drug was previously complexed with sulfobutyl ether-β-cyclodextrin, and then incorporated in the nanodroplet chitosan shell via electrostatic interaction. The acyclovir-cyclodextrin inclusion complex was characterized by phase solubility, DSC, FTIR studies. The nanodroplets showed an average diameter of about 400 nm and positive surface charge. Acyclovir was efficiently incorporated in the nanodroplets (about 97% of encapsulation efficiency) and slowly released over time. The acyclovir-loaded nanodroplets exhibited an enhanced antiviral activity compared to the free drug against HSV-2 in cell cultures, which might be ascribed to a higher intracellular accumulation of the drug in nanodroplet-treated cells than in free acyclovir-treated cells. Based on these results, this new nanoformulation paves the way for the development of a future nanomicrobicide for the HSV-2 infections. [ABSTRACT FROM AUTHOR]