Quality by Design Approach for the Development of Liposome Carrying Ghrelin for Intranasal Administration
The therapeutic use of peptides has increasingly recognized in the development of new therapies. However, the susceptible enzymatic cleavage is a barrier that needs to overcome. Nose-to-brain delivery associated with liposomes can protect peptides against biodegradation and improve the accessibility...
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| Format: | Article |
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MDPI AG
2021-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/5/686 |
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| author | Cecília de Barros Norberto Aranha Patrícia Severino Eliana B. Souto Aleksandra Zielińska André Lopes Alessandra Rios Fernando Batain Kessi Crescencio Marco Chaud Thais Alves |
| author_facet | Cecília de Barros Norberto Aranha Patrícia Severino Eliana B. Souto Aleksandra Zielińska André Lopes Alessandra Rios Fernando Batain Kessi Crescencio Marco Chaud Thais Alves |
| author_sort | Cecília de Barros |
| collection | DOAJ |
| description | The therapeutic use of peptides has increasingly recognized in the development of new therapies. However, the susceptible enzymatic cleavage is a barrier that needs to overcome. Nose-to-brain delivery associated with liposomes can protect peptides against biodegradation and improve the accessibility to brain targets. The aim was to develop a liposomal formulation as ghrelin carrier. The quality by design (QbD) approach was used as a strategy for method development. The initial risk assessments were carried out using a fishbone diagram. A screening design study was performed for the critical material attributes/critical process parameters (CMAs/CPPs) on critical quality attributes (CQAs). Liposomes were obtained by hydrating phospholipid films, followed by extrusion or homogenization, and coated with chitosan. The optimized liposome formulation was produced by high-pressure homogenization coated with chitosan, and the resulted were liposomes size 72.25 ± 1.46 nm, PDI of 0.300 ± 0.027, the zeta potential of 50.3 ± 1.46 mV, and encapsulation efficiency of 53.2%. Moreover, chitosan coating improved performance in ex vivo permeation and mucoadhesion analyzes when compared to the uncoated liposome. In this context, chitosan coating is essential for the performance of the formulations in the ex vivo permeation and mucoadhesion analyzes. The intranasal administration of ghrelin liposomes coated with chitosan offers an innovative opportunity to treat cachexia. |
| first_indexed | 2024-03-10T11:33:27Z |
| format | Article |
| id | doaj.art-302598937e064431bacffeacf1c8a267 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T11:33:27Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-302598937e064431bacffeacf1c8a2672023-11-21T19:02:49ZengMDPI AGPharmaceutics1999-49232021-05-0113568610.3390/pharmaceutics13050686Quality by Design Approach for the Development of Liposome Carrying Ghrelin for Intranasal AdministrationCecília de Barros0Norberto Aranha1Patrícia Severino2Eliana B. Souto3Aleksandra Zielińska4André Lopes5Alessandra Rios6Fernando Batain7Kessi Crescencio8Marco Chaud9Thais Alves10Laboratory of Biomaterials and Nanotechnology (LaBNUS), University of Sorocaba, Sorocaba 18078-005, São Paulo, BrazilTechnological and Environmental Processes, University of Sorocaba, Sorocaba 18078-005, São Paulo, BrazilNanomedicine and Nanotechnology Laboratory (LNMed), Institute of Technology and Research (ITP), Av. Murilo Dantas, 300, Aracaju 49010-390, Sergipe, BrazilDepartment of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Ciências da Saúde, 3000-548 Coimbra, PortugalInstitute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479 Poznan, PolandFaculty of Pharmaceutical Science, University of Campinas, Campinas 13083-871, São Paulo, BrazilLaboratory of Biomaterials and Nanotechnology (LaBNUS), University of Sorocaba, Sorocaba 18078-005, São Paulo, BrazilLaboratory of Biomaterials and Nanotechnology (LaBNUS), University of Sorocaba, Sorocaba 18078-005, São Paulo, BrazilLaboratory of Biomaterials and Nanotechnology (LaBNUS), University of Sorocaba, Sorocaba 18078-005, São Paulo, BrazilLaboratory of Biomaterials and Nanotechnology (LaBNUS), University of Sorocaba, Sorocaba 18078-005, São Paulo, BrazilLaboratory of Biomaterials and Nanotechnology (LaBNUS), University of Sorocaba, Sorocaba 18078-005, São Paulo, BrazilThe therapeutic use of peptides has increasingly recognized in the development of new therapies. However, the susceptible enzymatic cleavage is a barrier that needs to overcome. Nose-to-brain delivery associated with liposomes can protect peptides against biodegradation and improve the accessibility to brain targets. The aim was to develop a liposomal formulation as ghrelin carrier. The quality by design (QbD) approach was used as a strategy for method development. The initial risk assessments were carried out using a fishbone diagram. A screening design study was performed for the critical material attributes/critical process parameters (CMAs/CPPs) on critical quality attributes (CQAs). Liposomes were obtained by hydrating phospholipid films, followed by extrusion or homogenization, and coated with chitosan. The optimized liposome formulation was produced by high-pressure homogenization coated with chitosan, and the resulted were liposomes size 72.25 ± 1.46 nm, PDI of 0.300 ± 0.027, the zeta potential of 50.3 ± 1.46 mV, and encapsulation efficiency of 53.2%. Moreover, chitosan coating improved performance in ex vivo permeation and mucoadhesion analyzes when compared to the uncoated liposome. In this context, chitosan coating is essential for the performance of the formulations in the ex vivo permeation and mucoadhesion analyzes. The intranasal administration of ghrelin liposomes coated with chitosan offers an innovative opportunity to treat cachexia.https://www.mdpi.com/1999-4923/13/5/686ghrelinintranasal routliposomesquality by design (QbD)cachexiaundernourishment |
| spellingShingle | Cecília de Barros Norberto Aranha Patrícia Severino Eliana B. Souto Aleksandra Zielińska André Lopes Alessandra Rios Fernando Batain Kessi Crescencio Marco Chaud Thais Alves Quality by Design Approach for the Development of Liposome Carrying Ghrelin for Intranasal Administration Pharmaceutics ghrelin intranasal rout liposomes quality by design (QbD) cachexia undernourishment |
| title | Quality by Design Approach for the Development of Liposome Carrying Ghrelin for Intranasal Administration |
| title_full | Quality by Design Approach for the Development of Liposome Carrying Ghrelin for Intranasal Administration |
| title_fullStr | Quality by Design Approach for the Development of Liposome Carrying Ghrelin for Intranasal Administration |
| title_full_unstemmed | Quality by Design Approach for the Development of Liposome Carrying Ghrelin for Intranasal Administration |
| title_short | Quality by Design Approach for the Development of Liposome Carrying Ghrelin for Intranasal Administration |
| title_sort | quality by design approach for the development of liposome carrying ghrelin for intranasal administration |
| topic | ghrelin intranasal rout liposomes quality by design (QbD) cachexia undernourishment |
| url | https://www.mdpi.com/1999-4923/13/5/686 |
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