Pullulan microneedle patches for the efficient transdermal administration of insulin envisioning diabetes treatment

[Display omitted] •Dissolvable pullulan microneedles were successfully prepared by solvent casting.•Pullulan-insulin microneedles successfully penetrate through the skin.•Storage at 4, 20 and 40 °C maintained the secondary structure of insulin.•Pullulan microneedles deliver 87% of insulin, 120 min a...

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Veröffentlicht in:Carbohydrate polymers 2020-08, Vol.241, p.116314-116314, Article 116314
Hauptverfasser: Fonseca, Daniela F.S., Costa, Paulo C., Almeida, Isabel F., Dias-Pereira, Patrícia, Correia-Sá, Inês, Bastos, Verónica, Oliveira, Helena, Duarte-Araújo, Margarida, Morato, Manuela, Vilela, Carla, Silvestre, Armando J.D., Freire, Carmen S.R.
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container_end_page 116314
container_issue
container_start_page 116314
container_title Carbohydrate polymers
container_volume 241
creator Fonseca, Daniela F.S.
Costa, Paulo C.
Almeida, Isabel F.
Dias-Pereira, Patrícia
Correia-Sá, Inês
Bastos, Verónica
Oliveira, Helena
Duarte-Araújo, Margarida
Morato, Manuela
Vilela, Carla
Silvestre, Armando J.D.
Freire, Carmen S.R.
description [Display omitted] •Dissolvable pullulan microneedles were successfully prepared by solvent casting.•Pullulan-insulin microneedles successfully penetrate through the skin.•Storage at 4, 20 and 40 °C maintained the secondary structure of insulin.•Pullulan microneedles deliver 87% of insulin, 120 min after insertion.•Pullulan-insulin microneedles are non-cytotoxic towards human keratinocyte cells. The present study reports the fabrication of dissolvable microneedle (MN) patches using pullulan (PL), a water-soluble polysaccharide with excellent film-forming ability, for the transdermal administration of insulin, envisioning the non-invasive treatment of diabetes. PL MNs patches were successfully prepared by micromoulding and revealed good thermal stability (Tdmax = 294 °C) and mechanical properties (>0.15 N needle−1), penetrating skin up to 381 μm depth, as revealed by in vitro skin tests. After application into human abdominal skin in vitro, the MNs dissolved within 2 h releasing up to 87% of insulin. When stored at 4, 20 and 40 °C for 4 weeks, insulin was able to retain its secondary structure, as shown by circular dichroism spectropolarimetry. The prepared PL MNs were non-cytotoxic towards human keratinocytes, being suitable for skin application. These findings suggest that PL MNs have potential to deliver insulin transdermally, thus avoiding its subcutaneous administration.
doi_str_mv 10.1016/j.carbpol.2020.116314
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The present study reports the fabrication of dissolvable microneedle (MN) patches using pullulan (PL), a water-soluble polysaccharide with excellent film-forming ability, for the transdermal administration of insulin, envisioning the non-invasive treatment of diabetes. PL MNs patches were successfully prepared by micromoulding and revealed good thermal stability (Tdmax = 294 °C) and mechanical properties (&gt;0.15 N needle−1), penetrating skin up to 381 μm depth, as revealed by in vitro skin tests. After application into human abdominal skin in vitro, the MNs dissolved within 2 h releasing up to 87% of insulin. When stored at 4, 20 and 40 °C for 4 weeks, insulin was able to retain its secondary structure, as shown by circular dichroism spectropolarimetry. The prepared PL MNs were non-cytotoxic towards human keratinocytes, being suitable for skin application. 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The present study reports the fabrication of dissolvable microneedle (MN) patches using pullulan (PL), a water-soluble polysaccharide with excellent film-forming ability, for the transdermal administration of insulin, envisioning the non-invasive treatment of diabetes. PL MNs patches were successfully prepared by micromoulding and revealed good thermal stability (Tdmax = 294 °C) and mechanical properties (&gt;0.15 N needle−1), penetrating skin up to 381 μm depth, as revealed by in vitro skin tests. After application into human abdominal skin in vitro, the MNs dissolved within 2 h releasing up to 87% of insulin. When stored at 4, 20 and 40 °C for 4 weeks, insulin was able to retain its secondary structure, as shown by circular dichroism spectropolarimetry. The prepared PL MNs were non-cytotoxic towards human keratinocytes, being suitable for skin application. 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subjects Administration, Cutaneous
Diabetes Mellitus - drug therapy
Drug Delivery Systems - instrumentation
Glucans - chemistry
HaCaT Cells
Humans
Hypoglycemic Agents - administration & dosage
Insulin
Insulin - administration & dosage
Microneedles
Needles
Polysaccharides
Pullulan
Transdermal drug delivery
Transdermal Patch
title Pullulan microneedle patches for the efficient transdermal administration of insulin envisioning diabetes treatment
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