Sequential injection spectrophotometric determination of zinc(II) in pharmaceuticals based on zinc(II)–PAN in non-ionic surfactant medium

Women urgently need a self-initiated, multipurpose prevention technology (MPT) that simultaneously reduces their risk of acquiring HIV-1, HSV-2, and HPV (latter two associated with increased risk of HIV-1 acquisition) and prevents unintended pregnancy. Here, we describe a novel core-matrix intravaginal ring (IVR), the MZCL IVR, which effectively delivered the MZC combination microbicide and a contraceptive. The MZCL IVR contains four active pharmaceutical ingredients (APIs): MIV-150 (targets HIV), zinc acetate (ZA; targets HIV and HSV-2), carrageenan (CG; targets HPV and HSV-2), and levonorgestrel (LNG; targets unintended pregnancy). The elastomeric IVR body (matrix) was produced by hot melt extrusion of the non-water swellable elastomer, ethylene vinyl acetate (EVA-28), containing the hydrophobic small molecules, MIV-150 and LNG. The solid hydrophilic core, embedded within the IVR by compression, contained the small molecule ZA and the macromolecule CG. Hydrated ZA/CG from the core was released by diffusion via a pore on the IVR while the MIV-150/LNG diffused from the matrix continuously for 94 days (d) in vitro and up to 28d (study period) in macaques. The APIs released in vitro and in vivo were active against HIV-1ADA-M, HSV-2, and HPV16 PsV in cell-based assays. Serum LNG was at levels associated with local contraceptive effects. The results demonstrate proof-of-concept of a novel core-matrix IVR for sustained and simultaneous delivery of diverse molecules for the prevention of HIV, HSV-2 and HPV acquisition, as well as unintended pregnancy.

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“…A literature method for ZA [54] was optimized (Suppl. method 4), LLOQ: 0.1 μg/ 200 μl (volume plated in the well).…”

Section: Methodsmentioning

confidence: 99%

A novel intravaginal ring to prevent HIV-1, HSV-2, HPV, and unintended pregnancy

Ugaonkar

Wesenberg

Jolanta

et al. 2015

Journal of Controlled Release

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“…UV absorbance to obtain zinc content was measured at 555 nm using a Perkin-Elmer Lambda 2 UV/visible light spectrophotometer (47). Thirteen milligrams of test gel was mixed with 200 l of 1 N HCl in a 2-ml conical centrifuge tube and vortexed for 5 min.…”

Section: Formulation-preparative Methods (I) Carrageenan/zinc Acetatmentioning

confidence: 99%

Zinc Acetate/Carrageenan Gels Exhibit Potent Activity In Vivo against High-Dose Herpes Simplex Virus 2 Vaginal and Rectal Challenge

Fernández-Romero

Abraham

Rodríguez

et al. 2012

Antimicrob Agents Chemother

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Topical microbicides that block the sexual transmission of HIV and herpes simplex virus 2 (HSV-2) are desperately needed to reduce the incidence of HIV infections worldwide. Previously we completed phase 3 testing of the carrageenan-based gel Carraguard. Although the trial did not show that Carraguard is effective in preventing HIV transmission during vaginal sex, it did show that Carraguard is safe when used weekly for up to 2 years. Moreover, Carraguard has in vitro activity against human papillomavirus (HPV) and HSV-2 and favorable physical and rheological properties, which makes it a useful vehicle to deliver antiviral agents such as zinc acetate. To that end, we previously reported that a prototype zinc acetate carrageenan gel protects macaques against vaginal challenge with combined simian-human immunodeficiency virus reverse transcriptase (SHIV-RT). Herein, we report the safety and efficacy of a series of zinc acetate and/or carrageenan gels. The gels protected mice (75 to 85% survival; P < 0.001) against high-dose (10 6 -PFU) HSV-2 vaginal or rectal challenge. In contrast, zinc acetate formulated in HEC (hydroxyethylcellulose; or the Universal Placebo) failed to protect mice against the high-dose vaginal HSV-2 challenge (similar to aqueous zinc acetate solution and the placebo controls). The gels were found to be effective spreading gels, exhibited limited toxicity in vitro, caused minimal damage to the architecture of the cervicovaginal and rectal mucosae in vivo, and induced no increased susceptibility to HSV-2 infection in a mouse model. Our results provide a strong rationale to further optimize and evaluate the zinc acetate/carrageenan gels for their ability to block the sexual transmission of HIV and HSV-2.

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“…Samples were then filtered on a 0.22 m PVDF filter to remove AC and obtain a clear solution. Zinc was assayed as described (Arvand et al, 2007;Thanasarakhan et al, 2007). Briefly, one hundred microliters of sample containing Zn 2+ ions and 1 mL of ammonia buffer solution (pH 10) were placed in 10 mL volumetric flasks.…”

Section: Determination Of Zinc Content In Beadsmentioning

confidence: 99%

Removal of ciprofloxacin in simulated digestive media by activated charcoal entrapped within zinc-pectinate beads

Khoder

Tsapis

Huguet

et al. 2009

International Journal of Pharmaceutics

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Sequential injection spectrophotometric determination of zinc(II) in pharmaceuticals based on zinc(II)–PAN in non-ionic surfactant medium

Cited by 20 publications

References 18 publications

A novel intravaginal ring to prevent HIV-1, HSV-2, HPV, and unintended pregnancy

A novel intravaginal ring to prevent HIV-1, HSV-2, HPV, and unintended pregnancy

Zinc Acetate/Carrageenan Gels Exhibit Potent Activity In Vivo against High-Dose Herpes Simplex Virus 2 Vaginal and Rectal Challenge

Removal of ciprofloxacin in simulated digestive media by activated charcoal entrapped within zinc-pectinate beads

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