Príspevok sa zaoberá skúmaním vplyvu bežne používaných humektantov glycerolu (GL) a propylénglykolu (PG) na liberáciu alaptidu (ALA) z 3% (m/m) chitosanových (CHIT) hydrogélov v porovnaní s liberáciou alaptidu (ALA) z krému. Obsah GL a PG v jednotlivých hydrogéloch bol 5 %, 10 %, 15 % (m/m). Alaptid je regeneračne pôsobiaci syntetický derivát prolyl-leucyl-glycin amidu, zatiaľ používaný vo veterinárnej medicíne. Jeho obsah v skúmaných hydrogéloch a kréme bol 1 % (m/m). Experimenty boli vykonané in vitro v temperovanej permeačnej aparatúre. Množstvo uvoľneného ALA bolo merané spektrofotometricky pri 212 nm, po 14. dňoch od prípravy jednotlivých chitosanových hydrogélov a krému. ALA sa uvoľnil v nasledovných množstvách: 14,06 % sa uvoľnilo z krému; 36,54 % z hydrogélu s obsahom 5 % GL (m/m); 37,85 % z hydrogélu s 5 % PG (m/m); 38,37 % z hydrogélu bez obsahu GL a PG; 40,71 % z hydrogélu s obsahom 15 % GL (m/m); 41,21 % z hydrogélu s 10 % GL (m/m); 42,72 % ALA sa uvoľnilo z hydrogélu s 10 % PG (m/m); 43,78 % z hydrogélu s 15 % PG (m/m). V závere možno usúdiť, že prítomnosť GL a PG malo vplyv na liberáciu ALA z dermálnych polotuhých liekov.
The paper examines the effects of routinely used humectants of glycerol (GL) and propylene glycol (PG) on the liberation of alaptid (ALA) from 3% (m/m) chitosan (CHIT) hydrogels in comparison with the liberation of alaptid (ALA) from cream. The contents of GL and PG in the individual hydrogels were 5%, 10%, 15% (m/m). Alaptid is a regeneratively acting synthetic derivative of prolyl-leucyl-glycin amide, which is for the time being used in veterinary medicine. Its content in the hydrogels and cream under study was 1% (m/m). The experiments were performed in vitro in a tempered permeating apparatus. The amount of the released ALA was measured spectrophotometrically at 212nm, 14 day after the preparation of the individual chitosan hydrogels and cream. ALA was liberated in the following amounts: 14.06% was released from cream; 36.54% from hydrogel containing 5% GL (m/m); 37.85% from hydrogel with 5% PG (m/m); 38.37% from hydrogel not containing GL and PG; 40.71% from hydrogel containing 15% GL (m/m); 41.21% from hydrogel with 10% GL (m/m); 42.72% ALA was released from hydrogel with 10% PG (m/m); 43.78% from hydrogel with 15% PG (m/m). It can be concluded that the presence of GL and PG exerted effects on liberation of ALA from dermal semisolid preparations.
The modern drug alaptide, synthetic dipeptide, shows regenerative effects and effects on the epitelisation process. A commercial product consisting of 1% alaptide hydrophilic cream is authorised for use in veterinary practice. This study focuses on the formulation of alaptide into semi-synthetic polymer-based hydrogels. The aim of the present study is to prepare hydrogels and to evaluate the liberation of alaptide from hydrogels. The hydrogels were prepared on the basis of three gel-producing substances: methylcellulose, hydroxyethylcellulose and hydroxypropylcellulose. To enhance the drug release from hydrogel humectants, glycerol, propylene glycol and ethanol in various concentrations were evaluated. The permeation of the alaptide from gels into the acceptor solution was evaluated with the use of the permeable membrane neprophane. The amount of drug released from prepared hydrogels was determined spectrophotometrically. Hydrogels with optimal alaptide liberation properties were subjected to the study of rheological properties in the next phase. The optimal composition of hydrogel as established in this study was 1% alaptide + 3% hydroxyethylcellulose with the addition of 10% glycerol as humectant. Due to the advantageous properties of hydrogels in wounds, alaptide could be incorporated into a hydrogel base for use in veterinary medicine.
- Keywords
- alaptid, zvlhčovadla,
- MeSH
- Cellulose chemistry MeSH
- Peptides, Cyclic * pharmacokinetics MeSH
- Dermatologic Agents classification MeSH
- Epithelium drug effects MeSH
- Pharmaceutic Aids * MeSH
- Wound Healing drug effects MeSH
- MSH Release-Inhibiting Hormone MeSH
- Hydrogels * chemistry therapeutic use MeSH
- Neuropeptides MeSH
- Drug Liberation MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Keywords
- ALAPTID (VÚFB PRAHA),
- MeSH
- DNA biosynthesis MeSH
- Hepatectomy MeSH
- Rats MeSH
- Liver Regeneration drug effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
Predmetom príspevku je hodnotenie liberácie liečiva alaptid z gélov a jeho permeácia cez rôzne typy permeačných membrán. Pripravili sa gély na báze troch rôznych polymérov (3 % chitosan; 2,5 % hydroxypropylcelulóza; 3 % hydroxyetylcelulóza) v rôznej koncentrácii s prísadou humaktantov (5 %; 15 % propylénglykol a 0 % glycerol) a konzervantu 0,3 % Sepicide HBR a liečiva 1 % alaptid a gély bez liečiva. Prestup liečiva z gélov do akceptorového roztoku sa hodnotil cez nasledovné membrány: celofán, kuracia koža, zvlečená hadia koža a stena tenkého čreva. Z výsledkov merania bolo zistené najväčšie percento uvoľneného alaptidu cez stenu tenkého čreva, menej cez kuraciu kožu a najmenej sa uvoľnilo cez hadiu kožu. V práci sa hodnotili aj reologické vlastnosti pripravených hydrogélov. Pseudoplastický tok bol zistený iba v prípade hydrogélu na báze hydroxypropylcelulózy. Naopak to bolo pri hydrogéloch na báze chitosanu a hydroxyetylcelulózy, ktoré vykazovali výrazný tixotropný charakter a miera tixotropie sa s časom zväčšovala. Na základe výsledkov merania pH boli vzorky na báze chitosanu a hydroxypropylcelulózy vyhodnotené ako nevyhovujúce, nakoľko dosahovali nižšie hodnoty pH a mohli by spôsobiť podráždenie pokožky. Fyziologickým hodnotám pH kože zodpovedal hydrogél na báze hydroxyetylcelulózy a to i po 14. dňoch po príprave.
The paper evaluates the liberation of alaptide from gels through various types of permeable membranes. The gels were prepared on the basis of three different polymers (3% chitosan; 2.5% hydroxypropyl cellulose; 3% hydroxyethyl cellulose) in different concentrations with additions of humectants (5 %; 15% propylene glycol and 10% glycerol) and the preserving agent, 0.3% Sepicide HBR with 1% alaptide, and finally without the drug. The permeation of the drug from gels into the acceptor solution was evaluated with the use of the following membranes: the hydrophilic membrane from Chemosvit, the chicken skin, the stripped snakeskin, and the wall of the small intestine. The measurements showed that the highest percentage of the drug penetrated through the small intestine, a smaller percentage through the chicken skin, and the smallest amount through the snakeskin. Rheological properties of the prepared hydrogels were evaluated as well. The pseudo-plastic flow was only confirmed for the hydrogel prepared on the basis of hydroxypropyl cellulose. An utterly opposite situation was with the hydrogels prepared on the basis of chitosan and hydroxyethyl cellulose. They showed a significant thixotropic character and the degree of thixotropy increased with time. Based on the results of the pH measurement, the samples prepared on the basis of chitosan and hydroxypropyl cellulose have been shown to be inconvenient because they reached a lower pH and had a potential of causing skin irritation. The hydroxyethyl cellulose hydrogel matched the physiological values of skin pH even after 14 days since its preparation.
Alaptide is the active substance of the veterinary dermatological ointment ALAPTID and a potential drug in human medicine. Electronic circular dichroism spectroscopy (ECD), transparent spectral region optical rotation (OR), and ab initio calculations were employed to determine the absolute configuration of alaptide. No X-ray structural data determining the absolute configuration were available. It was not possible to employ vibrational circular dichroism spectroscopy (VCD), because alaptide was not sufficiently soluble in common solvents used in VCD spectroscopy to generate reliable spectra. Both ECD spectra and OR values of alaptide solution were in good agreement with predicted data and determined unambiguously the absolute configuration of alaptide synthesized from (S)-alanine as being (S).
- MeSH
- Circular Dichroism MeSH
- Peptides, Cyclic chemistry MeSH
- Protein Conformation MeSH
- Humans MeSH
- Neuropeptides chemistry MeSH
- Optical Rotation MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Keywords
- ALAPTID (VÚFB PRAHA),
- MeSH
- Dipeptides analogs & derivatives pharmacology chemical synthesis MeSH
- Chick Embryo MeSH
- Cyclohexanecarboxylic Acids analogs & derivatives pharmacology chemical synthesis MeSH
- Psychotropic Drugs pharmacology chemical synthesis MeSH
- Animals MeSH
- Check Tag
- Chick Embryo MeSH
- Animals MeSH
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.
- MeSH
- Peptides, Cyclic * chemistry pharmacology MeSH
- Skin * MeSH
- Membranes, Artificial * MeSH
- Nanoparticles chemistry MeSH
- Neuropeptides * chemistry pharmacology MeSH
- Permeability MeSH
- Swine MeSH
- Skin, Artificial * MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
We have prepared a candidate biocompatible construct for skin wound healing based on electrospun polycaprolactone (PCL) nanofibrous membranes. The membrane material was loaded either with L-arginine or with alaptide, or with a mixture of both bioactive components. Alaptide is a spirocyclic synthetic dipeptide, an analogue of melanocyte-stimulating hormone release-inhibiting factor. L-arginine is an amino acid with a basic guanidine side chain. It is a direct precursor of nitric oxide, which plays a pivotal role in skin repair. The presence and the distribution of the additives were proved with high-performance liquid chromatography, Fourier-transform infrared spectroscopy and Raman spectroscopy. The influence of L-arginine and alaptide on the morphology of the membrane was characterized using scanning electron microscopy. No statistically significant correlation between fiber diameter and drug concentration was observed. The membranes were then tested in vitro for their cytotoxicity, using primary human dermal fibroblasts, in order to obtain the optimal concentrations of the additives for in vivo tests in a rat model. The membranes with the highest concentration of L-arginine (10 wt. %) proved to be cytotoxic. The membranes with alaptide in concentrations from 0.1 to 2.5 wt.%, and with the other L-arginine concentrations (1 and 5 wt.%), did not show high toxicity. In addition, there was no observed improvement in cell proliferation on the membranes. The in vivo experiments revealed that membranes with 1.5 wt.% of alaptide or with 1.5 wt.% of alaptide in combination with 5 wt.% of L-arginine markedly accelerated the healing of skin incisions, and particularly the healing of skin burns, i.e. wounds of relatively large extent. These results indicate that our newly-developed nanofibrous membranes are promising for treating wounds with large damaged areas, where a supporting material is needed.
- MeSH
- Arginine chemistry MeSH
- Biocompatible Materials chemistry MeSH
- Peptides, Cyclic chemistry MeSH
- Electrochemistry MeSH
- Electrodes MeSH
- Fibroblasts drug effects MeSH
- Microscopy, Fluorescence MeSH
- Wound Healing drug effects MeSH
- Rats MeSH
- Skin pathology MeSH
- Humans MeSH
- Nanofibers chemistry MeSH
- Neuropeptides chemistry MeSH
- Peptides chemistry MeSH
- Rats, Wistar MeSH
- Cell Proliferation MeSH
- Spectrum Analysis, Raman MeSH
- Spectroscopy, Fourier Transform Infrared MeSH
- Drug Delivery Systems MeSH
- In Vitro Techniques MeSH
- Materials Testing MeSH
- Tissue Engineering methods MeSH
- Tissue Scaffolds chemistry MeSH
- Chromatography, High Pressure Liquid MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
