<i>In Vivo</i> Activity of Repurposed Amodiaquine as a Host-Targeting Therapy for the Treatment of Anthrax

Shilman, Mikhail Martchenko; Bartolo, Gloria; Alameh, Saleem; Peterson, Johnny W.; Lawrence, William S.; Peel, Jennifer E; Sivasubramani, Satheesh K.; Cote, Christopher K.; Demons, Samandra; Halasahoris, Stephanie A; Miller, Loren M.; Klimko, Christopher P.; Shoe, Jennifer L.; Fetterer, David P.; McComb, Ryan C.; Ho, Chi-Lee C.; Bradley, Kenneth A.; Hartmann, Stella; Cheng, Luisa W.; Chugunova, Marina; Kao, Chiu‐Yen; Tran, Jennifer; Derbedrossian, Aram; Zilbermintz, Leeor; Amali-Adekwu, Emiene; Levitin, Anastasia; West, Joel

doi:10.1021/acsinfecdis.1c00190

Cited by 2 publications

(1 citation statement)

References 62 publications

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“…However, despite these limitations, pharmacokinetics and metabolism of primaquine enantiomers have been shown to be similar in human volunteers and mice receiving a single oral dose ( 48 , 51 ). That was also true for the antimalarial amodiaquine, and in that case, drug exposure was predicted to be higher in humans than in mice ( 52 ). Our results show that, within the same biological system (the mouse), primaquine delivered through a nanochitosan formulation had improved pharmacokinetic characteristics compared to free primaquine.…”

Section: Discussionmentioning

confidence: 93%

A nanochitosan-D-galactose formulation increases the accumulation of primaquine in the liver

Gomes,

Ribeiro,

Sanches

et al. 2024

Antimicrob Agents Chemother

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Primaquine is the mainstream antimalarial drug to prevent Plasmodium vivax relapses. However, this drug can induce hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency. Nanostructure formulations of primaquine loaded with D-galactose were used as a strategy to target the drug to the liver and decrease the hemolytic risks. Nanoemulsion (NE-Pq) and nanochitosan (NQ-Pq) formulations of primaquine diphosphate containing D-galactose were prepared and characterized by their physicochemistry properties. Pharmacokinetic and biodistribution studies were conducted using Swiss Webster mice. A single dose of 10 mg/kg of each nanoformulation or free primaquine solution was administered by gavage to the animals, which were killed at 0.5, 1, 2, 4, 8, and 24 hours. Blood samples and tissues were collected, processed, and analyzed by high-performance liquid chromatography. The nanoformulation showed sizes around 200 nm (NE-Pq) and 400 nm (NQ-Pq) and physicochemical stability for over 30 days. Free primaquine solution achieved higher primaquine Cmax in the liver than NE-Pq or NQ-Pq at 0.5 hours. However, the half-life and mean residence time (MRT) of primaquine in the liver were three times higher with the NQ-Pq formulation than with free primaquine, and the volume distribution was four times higher. Conversely, primaquine’s half-life, MRT, and volume distribution in the plasma were lower for NQ-Pq than for free primaquine. NE-Pq, on the other hand, accumulated more in the lungs but not in the liver. Galactose-coated primaquine nanochitosan formulation showed increased drug targeting to the liver compared to free primaquine and may represent a promising strategy for a more efficient and safer radical cure for vivax malaria.

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Section: Discussionmentioning

confidence: 93%

A nanochitosan-D-galactose formulation increases the accumulation of primaquine in the liver

Gomes,

Ribeiro,

Sanches

et al. 2024

Antimicrob Agents Chemother

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Anthrax meningoencephalitis: A case report

Zhou,

Liu,

Yang

et al. 2024

Exp Ther Med

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The present study describes the case of a patient with anthrax meningoencephalitis with the aim of providing a scientific basis for the control of this disease. The cerebrospinal fluid and blood of the patient were tested for genes and Bacillus anthracis was detected. The patient's meningitis was cured following treatment. Tracing the route of infection, anthrax was detected on the chopping board of the rural cattle and sheep butcher shop where the patient had purchased meat. In 2018, the patient complained of intermittent nasal discharge for 11 days after brain injury and came to the Second People's Hospital of Liaocheng (Linqing, China). Considering the existence of cerebrospinal fluid rhinorrhea, the patient's cerebrospinal fluid biochemistry was assessed and showed low sugar and high protein levels, resulting in a diagnosis of bacterial encephalitis. This encephalitis was considered to be related to bacterial retrograde infection after cerebrospinal fluid rhinorrhea. It is required to strengthen the training of medical personnel according to guidelines and laws and improve the level of early detection, reporting and diagnosis, as well as timely treatment at medical institutions. There is an urgent need to intensify the education of the population regarding the awareness and prevention of the disease. For individuals involved in the breeding, slaughtering and processing of livestock, multiple measures need to be taken to comprehensively intervene and to enhance occupational protection awareness and disease prevention capabilities.

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In Vivo Activity of Repurposed Amodiaquine as a Host-Targeting Therapy for the Treatment of Anthrax

Cited by 2 publications

References 62 publications

A nanochitosan-D-galactose formulation increases the accumulation of primaquine in the liver

A nanochitosan-D-galactose formulation increases the accumulation of primaquine in the liver

Anthrax meningoencephalitis: A case report

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