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Pilot-scale production of expansile nanoparticles: Practical methods for clinical scale-up.

ABSTRACT: One of the foremost challenges in translating nanoparticle technologies to the clinic is the requirement to produce materials on a large-scale. Scaling nanoparticle production methods is often non-trivial, and the success of these endeavors is frequently governed by whether or not an intermediate level of production, i.e., "pilot-scale" production, can be achieved. Pilot-scale production at the one-liter scale serves as a proof-of-concept that large-scale production will be possible. Here, we describe the pilot-scale production of the expansile nanoparticle (eNP) technology including verification of activity and efficacy following scaleup. We describe the challenges of sonication-based emulsification procedures and how these were overcome by use of a Microfluidizer technology. We also describe the problem-solving process that led to pre-polymerization of the nanoparticle polymer-a fundamental change from the lab-scale and previously published methods. Furthermore, we demonstrate good control over particle diameter, polydispersity and drug loading and the ability to sterilize the particles via filtration using this method. To facilitate long-term storage of these larger quantities of particles, we investigated six lyoprotectants and determined that sucrose is the most compatible with the current system. Lastly, we demonstrate that these changes to the manufacturing method do not adversely affect the swelling functionality of the particles, their highly specific localization to tumors, their non-toxicity in vivo or their efficacy in treating established intraperitoneal mesothelioma xenografts.

SUBMITTER: Colby AH

PROVIDER: S-EPMC8489532 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundGiven the global nursing shortage and investments to scale-up the workforce, this study evaluated trends in annual student nurse enrolment, pre-service attrition between enrolment and registration, and factors that influence nurse production in Kenya.MethodsThis study used a mixed methods approach with data from the Regulatory Human Resources Information System (tracks initial student enrolment through registration) and the Kenya Health Workforce Information System (tracks deployment and demographic information on licensed nurses) for the quantitative analyses and qualitative data from key informant interviews with nurse training institution educators and/or administrators. Trends in annual student nurse enrolment from 1999 to 2010 were analyzed using regulatory and demographic data. To assess pre-service attrition between training enrolment and registration with the nursing council, data for a cohort that enrolled in training from 1999 to 2004 and completed training by 2010 was analyzed. Multivariate logistic regression was used to test for factors that significantly affected attrition. To assess the capacity of nurse training institutions for scale-up, qualitative data was obtained through key informant interviews.ResultsFrom 1999 to 2010, 23,350 students enrolled in nurse training in Kenya. While annual new student enrolment doubled between 1999 (1,493) and 2010 (3,030), training institutions reported challenges in their capacity to accommodate the increased numbers. Key factors identified by the nursing faculty included congestion at clinical placement sites, limited clinical mentorship by qualified nurses, challenges with faculty recruitment and retention, and inadequate student housing, transportation and classroom space. Pre-service attrition among the cohort that enrolled between 1999 and 2004 and completed training by 2010 was found to be low (6%).ConclusionTo scale-up the nursing workforce in Kenya, concurrent investments in expanding the number of student nurse clinical placement sites, utilizing alternate forms of skills training, hiring more faculty and clinical instructors, and expanding the dormitory and classroom space to accommodate new students are needed to ensure that increases in student enrolment are not at the cost of quality nursing education. Student attrition does not appear to be a concern in Kenya compared to other African countries (10 to 40%).

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Pilot-scale production of expansile nanoparticles: Practical methods for clinical scale-up.

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