Two-step generation of spirocyclic dipeptides from linear peptide ethyl ester precursors

This study is focused on in vitro permeation of the original Czech compound, a skin/mucosa tissue regeneration promoter, known under the international nonproprietary name “alaptide,” in micronized and nanonized forms. Alaptide showed a great potential for local applications for treatment and/or regeneration of the injured skin. The above mentioned technological modifications influence the permeation of alaptide through artificial or biological membranes, such as PAMPA or skin. The permeation of micronized and nanonized form of alaptide formulated to various semisolid pharmaceutical compositions through full-thickness pig ear skin using a Franz cell has been investigated in detail. In general, it can be concluded that the nanonized alaptide permeated through the skin less than the micronized form; different observations were made for permeation through the PAMPA system, where the micronized form showed lower permeation than the nanonized alaptide.

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“…Alaptide was synthesized by the standard process, as described above [4, 5, 8]. Then it was micronized.…”

Section: Methodsmentioning

confidence: 99%

In Vitro Permeation of Micronized and Nanonized Alaptide from Semisolid Formulations

Opatřilová

Černíková

Coufalová

et al. 2013

The Scientific World Journal

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“…Alaptide was synthesised according to the standard process [38]. All reagents were purchased from Aldrich and Merck.…”

Section: Preparation Of Alaptidementioning

confidence: 99%

Rapid Screening of Mupirocin Skin Permeation Modification by Micronized and Nanonized Alaptide

Jampílek

Opatřilová

2014

ADMET DMPK

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The investigation deals with the affection of permeation of mupirocin from the Bactroban® Leciva ointment through full-thickness pig ear skin by alaptide that was applied in micronized or nanonized form as a potential excipient. Alaptide, (S)-8-methyl-6,9-diazaspiro[4.5]decan-7,10-dione, was the original Czech compound. It was discovered that micronized alaptide significantly enhanced the permeation of mupirocin within 1 h after administration (approx. 5-fold). On the other hand, nanonized alaptide almost completely inhibited permeation of mupirocin from Bactroban® Leciva through the skin.Rapid primary screening showed that the two forms of alaptide differently influenced the depth and the rate of permeation/penetration of mupirocin into/through the skin, i.e., affect curative effect of mupirocin on/in skin immediately after application of drug formulation.

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“…Alaptide originally developed by Kasafirek was prepared according to Scheme 1 from protected L-alanine and ethyl ester of cycloleucine [21]. Due to the lack of active chromophore, the process of synthesis was extensively optimized using mass spectrometry.…”

Section: Resultsmentioning

confidence: 99%

Investigation of permeation of acyclovir through skin using alaptide

Černíková¹,

Bobáľ²,

Bobáľová³

et al. 2018

Acta Chromatographica

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The investigation deals with the affection of the permeation of acyclovir through full-thickness pig ear skin using a Franz diffusion cell from the donor vehicles of phosphate buffer (pH 7.4) and propylene glycol-water (1:1) using synthesised (S)-8-methyl-6,9-diazaspiro[4.5]decane-7,10-dione, alaptide as a transdermal permeation enhancer. Alaptide was applied in ratio 1:10 (w/w) relative to the amount of acyclovir. At the first hour after application, the permeated amount of acyclovir from propylene glycol-water system, simulating semisolid dosage forms, was ca. four-fold higher than from the formulation without alaptide. Despite that the enhancement ratio of alaptide in a steady state was 1.7, the pseudo-enhancement ratio of alaptide in the time range of first to third hour was 2.3. Both enhancement ratios indicate that alaptide modifies skin structure, while the short-term application of the alaptide formulation seems to be more advantageous.

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Two-step generation of spirocyclic dipeptides from linear peptide ethyl ester precursors

Cited by 16 publications

References 10 publications

In Vitro Permeation of Micronized and Nanonized Alaptide from Semisolid Formulations

In Vitro Permeation of Micronized and Nanonized Alaptide from Semisolid Formulations

Rapid Screening of Mupirocin Skin Permeation Modification by Micronized and Nanonized Alaptide

Investigation of permeation of acyclovir through skin using alaptide

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