Use of Minipig Skin Biopsy Model as an Innovative Tool to Design Topical Formulation to Achieve Desired Pharmacokinetics in Humans

Mitra, Amitava; Leyes, Aquiles; Manser, Kimberly; Roadcap, Brad; Mestre, Christine; Tatosian, Daniel; Jin, Lan; Uemura, Naoto

doi:10.1002/jps.24383

Cited by 11 publications

(10 citation statements)

References 23 publications

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“…Furthermore, for skin samples, the on-column DNase digestion seems to be insufficient for full digestion of the genomic DNA, and thus other strategies such as post-RNA-extraction DNase treatment should be considered. Although in the literature, there were no studies confirming our findings, we expected to obtain these results, as human and pig skin have similar characteristics in various aspects, but most importantly in morphology 11–19 . The results presented here showed that the domestic pig samples were indeed applicable as a model tissue for finding potentially good workflows for human skin experiments.…”

Section: Discussionsupporting

confidence: 78%

“…These characteristics outweigh the dissimilarities, such as higher vascularisation in human and higher fat content in pig skin 11–15 . Hence, domestic pig has successfully been used in studies regarding percutaneous absorption 11 , different skin injuries such as bite marks 16 , burns and autografting 17 , diseases such as melanoma 18 , and in toxicology studies 19 .…”

Section: Introductionmentioning

confidence: 99%

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Identification of an optimal method for extracting RNA from human skin biopsy, using domestic pig as a model system

Reimann

Abram

Kõks

et al. 2019

Sci Rep

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To evaluate skin tissue gene expression patterns correctly, extracting sufficient quantities of good quality RNA is essential. However, RNA extraction from skin tissue is challenging, as the hyaluronic acid-collagen matrix is extremely difficult to homogenize. Although there are multiple ways to extract RNA from skin, there are no comparative studies that identify the most critical steps, e.g. sample collection, storage and homogenization. We analysed the various steps involved in RNA extraction (i.e. biopsy collection as dry biopsy or into nucleotide stabilizing reagents, different storage conditions, enzymatic digestion, stator-rotor and bead motion-based homogenizing combined with column-based RNA purification). We hypothesised that domestic pig skin is applicable as a model for human skin studies. Altogether twenty different workflows were tested on pig skin and the four most promising workflows were tested on human skin samples. The optimal strategy for extracting human skin RNA was to collect, store and homogenize the sample in RLT lysis buffer from the RNeasy Fibrous Tissue Kit combined with beta-mercaptoethanol. Both stator-rotor and bead motion-based homogenizing were found to result in high quality and quantity of extracted RNA. Our results confirmed that domestic pig skin can be successfully used as a model for human skin RNA studies.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Identification of an optimal method for extracting RNA from human skin biopsy, using domestic pig as a model system

Reimann

Abram

Kõks

et al. 2019

Sci Rep

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“…As well, a new method for pediatric liver transplantation was validated using pigs ( Leal et al, 2015 ). Regarding pharmacokinetic and cytotoxic tests, pigs have been used for testing topical skin formulations ( Mitra et al, 2015 ), and are considered a better choice compared to dogs for the study of drugs that are metabolized by the aldehyde oxidase (AOX1), N -acetyltransferase (NAT1 or NAT2) or cytochrome (CYP2C9-like) enzymes ( Dalgaard, 2014 ).…”

Section: Use Of Pigs In Biomedical Researchmentioning

confidence: 99%

Efficacy of the porcine species in biomedical research

et al. 2015

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Since domestication, pigs have been used extensively in agriculture and kept as companion animals. More recently they have been used in biomedical research, given they share many physiological and anatomical similarities with humans. Recent technological advances in assisted reproduction, somatic cell cloning, stem cell culture, genome editing, and transgenesis now enable the creation of unique porcine models of human diseases. Here, we highlight the potential applications and advantages of using pigs, particularly minipigs, as indispensable large animal models in fundamental and clinical research, including the development of therapeutics for inherited and chronic disorders, and cancers.

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“…The minipig has been used as a model in the development of dermatological products (Mitra et al, 2015;Yamamoto et al, 2017), and more recently, as a model for microbiome studies (Ericsson, 2019). As omnivores with an analogous gastrointestinal tract to humans, the well-characterized fecal microbiota of young and adult domestic pigs and other strains used in research also offers compositional resemblances to that of humans (Pedersen et al, 2013b;Zhao et al, 2015).…”

Section: Skinmentioning

confidence: 99%

Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do

Ribitsch

Baptista

Consiglio

et al. 2020

Front. Bioeng. Biotechnol.

158

110

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Rapid developments in Regenerative Medicine and Tissue Engineering has witnessed an increasing drive toward clinical translation of breakthrough technologies. However, the progression of promising preclinical data to achieve successful clinical market authorisation remains a bottleneck. One hurdle for progress to the clinic is the transition from small animal research to advanced preclinical studies in large animals to test safety and efficacy of products. Notwithstanding this, to draw meaningful and reliable conclusions from animal experiments it is critical that the species and disease model of choice is relevant to answer the research question as well as the clinical problem. Selecting the most appropriate animal model requires in-depth knowledge of specific species and breeds to ascertain the adequacy of the model and outcome measures that closely mirror the clinical situation. Traditional reductionist approaches in animal experiments, which often do not sufficiently reflect the studied disease, are still the norm and can result in a disconnect in outcomes observed between animal studies and clinical trials. To address these concerns a reconsideration in approach will be required. This should include a stepwise approach using in vitro and ex vivo experiments as well as in silico modeling to minimize the need for in vivo studies for screening and early development studies, followed by large animal models which more closely resemble human disease. Naturally occurring, or spontaneous diseases in large animals remain a largely untapped resource, and given the similarities in pathophysiology to humans they not only allow for studying new treatment strategies but also disease etiology and prevention. Naturally occurring disease models, particularly for longer lived large animal species, allow for studying disorders at an age when the disease is most prevalent. As these diseases are usually also a concern in the chosen veterinary species they would be beneficiaries of newly developed therapies. Improved awareness of the progress

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Use of Minipig Skin Biopsy Model as an Innovative Tool to Design Topical Formulation to Achieve Desired Pharmacokinetics in Humans

Cited by 11 publications

References 23 publications

Identification of an optimal method for extracting RNA from human skin biopsy, using domestic pig as a model system

Identification of an optimal method for extracting RNA from human skin biopsy, using domestic pig as a model system

Efficacy of the porcine species in biomedical research

Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do

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