260
only for a restricted array of viruses. A number of nanocarriers,
either inorganic or organic, have been developed to improve the
delivery and therapeutic efficacy of antiviral medicines and
cyclodextrin- based polymers represent a promising strategy to
improve antiviral treatments [59].
Acyclovir (ACV) was the first antiviral to be licensed for the
treatment of HSV infections, and it is the drug of choice for the
treatment of epidermal, ocular, or systemic herpetic infections.
ACV is slightly soluble in water and has a short plasma half-life, its
absorption from gastrointestinal tract is slow and incomplete, and
oral bioavailability reaches to a max of 30%. As a consequence,
higher doses are prescribed, resulting in systemic toxicity and
adverse reactions. ACV bioavailability is low and highly variable,
associated with low retention at the vaginal mucosa and poor
patient compliance, and requires frequent administrations [60].
Novel polymeric nanoparticles based on a β-cyclodextrinpoly(4-acryloylmorpholine) mono-conjugate (β-CD-PACM), a
tadpole-shaped polymer in which the β-CD ring is the hydrophilic
head and the PACM chain, the amphiphilic tail, were prepared by
the solvent injection technique. The antiviral activity of acyclovir
loaded into β-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 β-CD-PACM
complex. It was also found that the nanoparticles are internalized
in cells and are located in the perinuclear compartment [61].
In an alternative study, new Carb-NS were purposely prepared
as the carrier for acyclovir. Carb-NS were obtained by reacting succinic anhydride on preformed NS in DMSO at 90 °C for 3 h. The
solid NS was recovered by filtration and washed with a large
amount of water. Fluorescent Carb-NS were also synthesized for
cellular trafficking studies (Fig. 4). For this purpose, preformed NS
were added to a fluorescein isothiocyanate solution in DMSO and
incubated at 90 °C for 3 h. The filtered, washed, and dried product
was reacted with the succinic anhydride to obtain fluorescent
Carb-NS [62]. The drug loading percentage for Carb-NS was 69%
(w/w), ascribed to the presence of the acid groups in the Carb-NS
structure acting as further sites for acyclovir electrostatic interactions besides the cyclodextrin cavities. The antiviral activity was
performed using monolayers of Vero cells infected with a clinical
isolate of HSV-1. The dose–response curve obtained demonstrates
that the antiviral potency of the acyclovir-loaded Carb-NS was
higher than that of free acyclovir. The percent enhancement of cellular uptake of acyclovir formulations in Vero cells compared to
that of the plain drug was approximately more than 200% for
Carb-NS. Carb-NS showed enhanced drug loading and more prolonged release kinetics in comparison with traditional NS [61].
Considering the biocompatibility of nanosponges, the developMaria Tannous et al.
only for a restricted array of viruses. A number of nanocarriers,
either inorganic or organic, have been developed to improve the
delivery and therapeutic efficacy of antiviral medicines and
cyclodextrin- based polymers represent a promising strategy to
improve antiviral treatments [59].
Acyclovir (ACV) was the first antiviral to be licensed for the
treatment of HSV infections, and it is the drug of choice for the
treatment of epidermal, ocular, or systemic herpetic infections.
ACV is slightly soluble in water and has a short plasma half-life, its
absorption from gastrointestinal tract is slow and incomplete, and
oral bioavailability reaches to a max of 30%. As a consequence,
higher doses are prescribed, resulting in systemic toxicity and
adverse reactions. ACV bioavailability is low and highly variable,
associated with low retention at the vaginal mucosa and poor
patient compliance, and requires frequent administrations [60].
Novel polymeric nanoparticles based on a β-cyclodextrinpoly(4-acryloylmorpholine) mono-conjugate (β-CD-PACM), a
tadpole-shaped polymer in which the β-CD ring is the hydrophilic
head and the PACM chain, the amphiphilic tail, were prepared by
the solvent injection technique. The antiviral activity of acyclovir
loaded into β-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 β-CD-PACM
complex. It was also found that the nanoparticles are internalized
in cells and are located in the perinuclear compartment [61].
In an alternative study, new Carb-NS were purposely prepared
as the carrier for acyclovir. Carb-NS were obtained by reacting succinic anhydride on preformed NS in DMSO at 90 °C for 3 h. The
solid NS was recovered by filtration and washed with a large
amount of water. Fluorescent Carb-NS were also synthesized for
cellular trafficking studies (Fig. 4). For this purpose, preformed NS
were added to a fluorescein isothiocyanate solution in DMSO and
incubated at 90 °C for 3 h. The filtered, washed, and dried product
was reacted with the succinic anhydride to obtain fluorescent
Carb-NS [62]. The drug loading percentage for Carb-NS was 69%
(w/w), ascribed to the presence of the acid groups in the Carb-NS
structure acting as further sites for acyclovir electrostatic interactions besides the cyclodextrin cavities. The antiviral activity was
performed using monolayers of Vero cells infected with a clinical
isolate of HSV-1. The dose–response curve obtained demonstrates
that the antiviral potency of the acyclovir-loaded Carb-NS was
higher than that of free acyclovir. The percent enhancement of cellular uptake of acyclovir formulations in Vero cells compared to
that of the plain drug was approximately more than 200% for
Carb-NS. Carb-NS showed enhanced drug loading and more prolonged release kinetics in comparison with traditional NS [61].
Considering the biocompatibility of nanosponges, the developMaria Tannous et al.