Joseph T. Persyn

Microcapsule-gel formulation of promethazine HCl for controlled nasal delivery: A motion sickness medication

The current method of choice for astronauts to treat space motion sickness is an intra-muscular injection of promethazine hydrochloride (PMZ HCl) which is invasive and causes considerable local irritation and discomfort at the site of injection. Intra-nasal delivery is considered a feasible alternative route for administration of medications to treat space motion sickness. The purpose of this research is to develop a PMZ HCl formulation that can be administered intra-nasally without irritation (i.e. leukocyte infiltration) in the nasal epithelium when dosed at PMZ HCl concentrations greater than the cytotoxic limit. The biocompatibility of PMZ HCl was tested in vitro and was shown to be cytotoxic at concentrations greater than 10−5 molar regardless of pH. A controlled-release microencapsulated dosage formulation was developed using spinning disk atomization and release rates for the PMZ HCl microcapsules were determined in phosphate buffered saline. An animal study was conducted to determine the irritation response of rat nasal mucosa when dosed with encapsulated and non-encapsulated PMZ HCl.

Protecting Chickens Against Coccidiosis in Floor Pens by Administering Eimeria Oocysts Using Gel Beads or Spray Vaccination

SUMMARY Control of avian coccidiosis is increasingly being achieved by the administration of low doses of Eimeria oocysts to newly hatched chicks. The purpose of this study was to test the efficacy of gel beads containing a mixture of Eimeria acervulina, Eimeria maxima, and Eimeria tenella oocysts as a vaccine to protect broilers raised in contact with litter. Newly hatched chicks were either sprayed with an aqueous suspension of Eimeria oocysts or were allowed to ingest feed containing Eimeria oocysts-incorporated gel beads. Control, 1-day-old chicks were given an equivalent number of Eimeria oocysts (103 total) by oral gavage or received no vaccine (nonimmunized controls). All chicks were raised in floor-pen cages in direct contact with litter. At 4 wk of age, all chickens and a control nonimmunized group received a high-dose E. acervulina, E. maxima, and E. tenella challenge infection. Chickens immunized with Eimeria oocysts in gel beads or by spray vaccination displayed significantly (P < 0.05) greater weight gain (WG) compared to nonimmunized controls. Feed conversion ratio (FCR) also showed a significant (P < 0.05) improvement in both groups relative to nonimmunized controls. Moreover, WG and FCR in both groups was not significantly different (P > 0.05) from chickens immunized by oral gavage or from nonimmunized, noninfected controls. Oocyst excretion after Eimeria challenge by all immunized groups was about 10-fold less than in nonimmunized controls. These findings indicate that immunization efficacy of gel beads and spray vaccination is improved by raising immunized chicks in contact with litter. RESUMEN Protección de los pollos contra la coccidiosis en corrales de piso mediante la administración de ooquistes de Eimeria utilizando perlas de gel o por vacunación en aerosol. El control de la coccidiosis aviar se lleva a cabo cada vez más mediante la administración de dosis bajas de oocistos de Eimeria a pollitos recién nacidos. El propósito de este estudio fue evaluar la eficacia de las perlas de gel que contienen una mezcla de ooquistes de Eimeria acervulina, Eimeria maxima y Eimeria tenella como una vacuna para proteger pollos criados sobre cama. Pollitos recién nacidos fueron ya sea sometidos a aerosoles con una suspensión acuosa de ooquistes de Eimeria o se les permitió ingerir alimentos que contenían ooquistes de Eimeria incorporados en perlas de gel. A los pollos de un día de edad del grupo control, se les administró un número equivalente de ooquistes de Eimeria (103 en total) por sonda oral o no recibieron ninguna vacuna (controles no inmunizados). Todos los pollos fueron criados en corrales en contacto directo con la cama. A las cuatro semanas de edad, todos los pollos y el grupo control no inmunizado fueron desafiados con una dosis alta de E. acervulina, E. maxima y E. tenella. Los pollos inmunizados con ooquistes de Eimeria en perlas de gel o mediante vacunación por aerosol mostraron una mayor ganancia de peso, de manera significativa (P <0.05), en comparación con los controles no inmunizados. La tasa de conversión alimenticia (FCR) también mostró una mejora significativa (P <0.05) en los dos grupos en comparación con los controles no inmunizados. Por otra parte, la ganancia de peso y la conversión alimenticia en los dos grupos no fue significativamente diferente (P> 0.05) a partir de pollos inmunizados por sonda oral o de los controles no inmunizados y no infectados. La excreción de ooquistes de Eimeria después del desafío para todos los grupos inmunizados fue aproximadamente 10 veces menos que en los controles no inmunizados. Estos hallazgos indican que la eficacia de la inmunización de perlas de gel y la vacunación por aerosol se mejora mediante el contacto de los pollos de los pollos inmunizados con la cama.

Mucosal delivery of cytotoxic therapeutic agents: Response of rat nasal mucosa to microencapsulated ethopropazine HCl enantiomer

Use of microencapsulation technology in combination with absorption enhancers eliminated epithelium irritation and necrosis commonly associated with nasal delivery of cytotoxic therapeutic agents. Phenothiazines, such as ethopropazine (ETZ), promethazine, trimeprazine and propiomazine have been used for the treatment of allergenic conditions, motion sickness, nausea, Parkinsons disease, Prion disease and as a sedative for psychiatric disorders. The enantiomers of commercially available racemic phenothiazines were isolated and purified using classical diastereomeric salt techniques. The racemate and the enantiomers of ETZ were tested in vitro for their cellular toxicity using lung fibroblast cells. Each enantiomer was shown to be cytotoxic at concentrations greater than 10−5 molar. The ETZ enantiomers were encapsulated using spinning disk atomization to prepare a nasal delivery dosage form that does not produce an irritation response. Release rates for the ETZ microcapsules were determined in vitro and an animal study was conducted to determine the irritation response of rat nasal mucosa when dosed with encapsulated vs. non-encapsulated ETZ.