<abstract xmlns="http://www.w3.org/1999/xhtml"><sec><h3>Background</h3><p>The aim of this study was to obtain chitosan hydrogels containing megosin, an antiviral medicinal substance, to prolong its bioavailability. Megosin as an immunomodulating agent possesses at least twice higher virostatic and virucidal activities than gossypol, the megosin precursor, and other imine derivatives of gossypol.</p></sec><sec><h3>Materials and Methods</h3><p>Chitosan, used in this paper, was obtained by deacetylation of chitin; megosin was obtained on the bases of gossypol. Different concentrations of sodium tripolyphosphate (STPP) were used as the cross-linking agent. The release of megosin from hydrogel samples into blood was conducted on five white rats in four groups.</p></sec><sec><h3>Results</h3><p>Infrared spectral data demonstrated cross-linkage that the band responsible for NH bending of the uncross-linked chitosan reduced its intensity and moved to a lower wavelength, 1636 cm<sup>−1</sup>. It has been proven that megosin contained in gels does not penetrate into the blood and organs after vaginal administration. Release kinetics of megosin from chitosan hydrogels revealed that within 7 h, up to 52% of megosin is allowed into acidic solution (pH 4.5).</p></sec><sec><h3>Conclusion</h3><p>This study demonstrates the possibility to prolong bioavailability of megosin for at least 7 h, during which time it is not released into blood. The obtained results show the possibility to use the gel composition to treat vaginal herpes.</p></sec></abstract>

BackgroundThe aim of this study was to obtain chitosan hydrogels containing megosin, an antiviral medicinal substance, to prolong its bioavailability. Megosin as an immunomodulating agent possesses at least twice higher virostatic and virucidal activities than gossypol, the megosin precursor, and other imine derivatives of gossypol.Materials and MethodsChitosan, used in this paper, was obtained by deacetylation of chitin; megosin was obtained on the bases of gossypol. Different concentrations of sodium tripolyphosphate (STPP) were used as the cross-linking agent. The release of megosin from hydrogel samples into blood was conducted on five white rats in four groups.ResultsInfrared spectral data demonstrated cross-linkage that the band responsible for NH bending of the uncross-linked chitosan reduced its intensity and moved to a lower wavelength, 1636 cm−1. It has been proven that megosin contained in gels does not penetrate into the blood and organs after vaginal administration. Release kinetics of megosin from chitosan hydrogels revealed that within 7 h, up to 52% of megosin is allowed into acidic solution (pH 4.5).ConclusionThis study demonstrates the possibility to prolong bioavailability of megosin for at least 7 h, during which time it is not released into blood. The obtained results show the possibility to use the gel composition to treat vaginal herpes.


<div xmlns="http://www.w3.org/1999/xhtml"><sec id="j_afpuc-2020-0006_s_001_w2aab3b7c30b1b6b1ab1aAa"><div>INTRODUCTION</div><p>One of the most common diseases of viral etiology is genital herpes (<a ref-type="bibr" href="#j_afpuc-2020-0006_ref_001_w2aab3b7c30b1b6b1ab2b1b1Aa">Sauerbrei, 2016</a>). Acyclic nucleoside antiviral drugs such as acyclovir, valacyclovir, and famciclovir have long been used effectively to treat genital herpes (<a ref-type="bibr" href="#j_afpuc-2020-0006_ref_002_w2aab3b7c30b1b6b1ab2b1b2Aa">Pasternak 2010</a>). However, an increasing number of viruses resistant to acyclovir and similar drugs have recently appeared. It was found that in patients with recurrent herpes, the process of formation of interferon is significantly reduced in comparison with healthy people (<a ref-type="bibr" href="#j_afpuc-2020-0006_ref_001_w2aab3b7c30b1b6b1ab2b1b1Aa">Sauerbrei, 2016</a>). Therefore, in the treatment of herpes, endogenous interferon inducers have been paid more attention (<a ref-type="bibr" href="#j_afpuc-2020-0006_ref_004_w2aab3b7c30b1b6b1ab2b1b4Aa">Katzenel and Leib, 2016</a>; <a ref-type="bibr" href="#j_afpuc-2020-0006_ref_003_w2aab3b7c30b1b6b1ab2b1b3Aa">Rasmussen et al., 2007</a>).</p><p>Interferons lower the proliferation of herpes virus <italic>in vitro</italic>. Therefore, topical application of gels containing interferon α inducers, several times a day, is a relatively effective treatment for genital herpes (<a ref-type="bibr" href="#j_afpuc-2020-0006_ref_005_w2aab3b7c30b1b6b1ab2b1b5Aa">Shperling and Sharopina, 2009</a>). The other effective antiviral drug, megosin (<a ref-type="fig" href="#j_afpuc-2020-0006_fig_001_w2aab3b7c30b1b6b1ab1ab3Aa">Fig. 1</a>), is able to induce α, β, γ interferons in the body. Therefore, megosin, affecting the interferon system, exerts its indirect antiviral effect (<a ref-type="bibr" href="#j_afpuc-2020-0006_ref_006_w2aab3b7c30b1b6b1ab2b1b6Aa">Baram et al., 2004</a>).</p><figure id="j_afpuc-2020-0006_fig_001_w2aab3b7c30b1b6b1ab1ab3Aa" position="float" fig-type="figure"><h2>Figure 1</h2><figCaption><p>Structure of megosin</p></figCaption><img xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/j_afpuc-2020-0006_fig_001.jpg" src="https://sciendo-parsed.s3.eu-central-1.amazonaws.com/6470849271e4585e08a9f0af/j_afpuc-2020-0006_fig_001.jpg?X-Amz-Algorithm=AWS4-HMAC-SHA256&amp;X-Amz-Date=20240730T134124Z&amp;X-Amz-SignedHeaders=host&amp;X-Amz-Expires=18000&amp;X-Amz-Credential=AKIA6AP2G7AKP25APDM2%2F20240730%2Feu-central-1%2Fs3%2Faws4_request&amp;X-Amz-Signature=2174fe32a9d34c7d9a59b996fb93859feca3c6d948055292675e1822852c3a4c" class="mw-100"/></figure><p>Ordinary conventional vaginal delivery systems like creams, foams, and gels cannot remain for a longer time within the body due to self-cleaning of the vaginal tract. This reduces the retention period of the drug, increases the dose and frequency of drug, and consequently leads to inconvenience when used. Thus, chitosan, a natural cationic amino polysaccharide, used in medicine and pharmaceutics due to its properties such as biodegradability (<a ref-type="bibr" href="#j_afpuc-2020-0006_ref_007_w2aab3b7c30b1b6b1ab2b1b7Aa">Kumar et al., 2004</a>), biocompatibility, lack of toxicity, mucoadhesion (<a ref-type="bibr" href="#j_afpuc-2020-0006_ref_009_w2aab3b7c30b1b6b1ab2b1b9Aa">Aranaz et al., 2009</a>; <a ref-type="bibr" href="#j_afpuc-2020-0006_ref_008_w2aab3b7c30b1b6b1ab2b1b8Aa">Sonia and Sharma, 2011</a>), and ability to exert antioxidant (<a ref-type="bibr" href="#j_afpuc-2020-0006_ref_010_w2aab3b7c30b1b6b1ab2b1c10Aa">Ngo et al., 2014</a>), antibacterial (<a ref-type="bibr" href="#j_afpuc-2020-0006_ref_011_w2aab3b7c30b1b6b1ab2b1c11Aa">Martins et al., 2014</a>), and antiviral effects (<a ref-type="bibr" href="#j_afpuc-2020-0006_ref_012_w2aab3b7c30b1b6b1ab2b1c12Aa">Ai et al., 2008</a>), is expected to be an efficient agent.</p><p>The synergy of the antibacterial properties of chitosan and the antiviral properties of megosin will provide a more effective treatment of genital herpes. The use of mucoadhesive vaginal gel with a slow release of the megosin prolongs the action of the drug and improves bioavailability (<a ref-type="bibr" href="#j_afpuc-2020-0006_ref_013_w2aab3b7c30b1b6b1ab2b1c13Aa">Yellanki et al., 2010</a>). In combination with medicinal substances, chitosan is able to prolong their action (<a ref-type="bibr" href="#j_afpuc-2020-0006_ref_014_w2aab3b7c30b1b6b1ab2b1c14Aa">Ahmadi et al., 2015</a>).</p><p>The aim of the work is to develop a vaginal gel with mucoadhesive, antibacterial, and antiviral properties to provide longer action at the site of infection using the natural polymer chitosan and the antiviral drug megosin.</p></sec><sec id="j_afpuc-2020-0006_s_002_w2aab3b7c30b1b6b1ab1b1Aa"><div>MATERIALS AND METHODS</div><p>Megosin was obtained from Institute of Bioorganic Chemistry, Academy of Sciences of Uzbekistan. All other reagents were of analytical grade and used without any further purification.</p><sec id="j_afpuc-2020-0006_s_002_s_001_w2aab3b7c30b1b6b1ab1b1b2Aa"><div>Preparation of a vaginal gel</div><p>Megosin gel was prepared using chitosan as a gelling agent. Chitosan was dispersed in acetic acid (1%–4%) and was then left overnight to provide complete solubility. Megosin was initially dissolved in 50% ethanol and added to the polymer base with continuous stirring. Two milliliters of an aqueous solution of sodium tripolyphosphate (STPP) (1.4%–5.6%) was added to 10 ml of a chitosan solution of a certain concentration in an aqueous solution of acetic acid at constant stirring.</p></sec><sec id="j_afpuc-2020-0006_s_002_s_002_w2aab3b7c30b1b6b1ab1b1b3Aa"><div>Quantification of megosin</div><p>An exact amount of the gel was weighed and dissolved in 0.1% acetic acid with lauryl sulfate (1% w/v). After appropriate dilution, the megosin content was analyzed spectrophotometrically (UV-5100 / Vis, Metash, China) at 384 nm.</p></sec><sec id="j_afpuc-2020-0006_s_002_s_003_w2aab3b7c30b1b6b1ab1b1b4Aa"><div>Obtaining chitosan from chitin</div><p>Chitosan was obtained by deacetylation of chitin. An exact amount of chitin (from Sigma), ground until 0.2–0.3 mm, was treated with 120 ml 50% NaOH at 130°C for 1 h. Chitosan was washed out with water until its pH reached 5; it was then centrifuged and dried. The degree of deacetylation was determined by potentiometric titration. For that, an exact amount of chitosan was diluted in 20 ml of 0.1 M HCl and the obtained solution was titrated with 0.05 M NaOH by adding 0.1 ml solution, stirring every 30 seconds (<a ref-type="bibr" href="#j_afpuc-2020-0006_ref_015_w2aab3b7c30b1b6b1ab2b1c15Aa">Czechowska-Biskup et al., 2012</a>).</p></sec><sec id="j_afpuc-2020-0006_s_002_s_004_w2aab3b7c30b1b6b1ab1b1b5Aa"><div>Kinetics of megosin release from the gel</div><p>Exact amounts of gel samples were placed in a dialysis bag (Serva Feinbiochemica D-6900, 16 × 0.5 m), permeable to passage of substances with a MW less than 10 kDa, and dialyzed against 0.58 mM lactic acid (pH 4.5) and kept at a temperature of 37°C. At certain time intervals, aliquots from the solution were taken and the quantity of the released megosin was determined spectrophotometrically at 384 nm. The calibration curve for megosin was established.</p></sec><sec id="j_afpuc-2020-0006_s_002_s_005_w2aab3b7c30b1b6b1ab1b1b6Aa"><div>Stability of megosin</div><p>Megosin was extracted from the freeze-dried gels with a mixture of acetone and water (7:3 v/v). The obtained samples of extracts were analyzed by HPLC (Agilent Technologies 1200 chromatographer with DAD detector. Column: 9.4 × 250 mm Eclipse XDB C18, 5 μm. Mobile phase: A—0.1% trifluoroacetic acid, B—acetonitrile. The flow rate is 2.5 ml/min). We used 10% to 15% acetonitrile as gradient elution for 28 minutes, absorption at 254 nm, referent—360 nm.</p></sec><sec id="j_afpuc-2020-0006_s_002_s_006_w2aab3b7c30b1b6b1ab1b1b7Aa"><div>Infrared spectra</div><p>Infrared spectra of megosin, chitosan, and the hydrogel on their bases were measured at room temperature on a Fourier infrared spectrometer (Prestige 21, Shimadzu, Japan) with a resolution of 2 cm<sup>−1</sup> and number of scans of 60. Samples were prepared by standard methods in a matrix of fused NaCl.</p></sec><sec id="j_afpuc-2020-0006_s_002_s_007_w2aab3b7c30b1b6b1ab1b1b8Aa"><div>Penetration of megosin from chitosan hydrogel into blood</div><p>One gram of gel containing 100 μg megosin was introduced intervaginally to white rats weighing 180–200 g. After 7 h, the rats were decapitated and blood, kidneys, and liver samples were collected. Blood and organs were lyophilized, crushed, and extracted with acetone: water solution (3:1, v/v). Quantity analysis of megosin was carried out by HPLC.</p></sec></sec><sec id="j_afpuc-2020-0006_s_003_w2aab3b7c30b1b6b1ab1b2Aa"><div>RESULTS AND DISCUSSION</div><p>The degree of deacetylation of chitosan was 88%. The alkali amount required for linkage with amino groups of chitosan was determined based on graphs of electrical conductivity in the exact amount of the solution.</p><p>We obtained megosin-containing chitosan hydrogels cross-linked with STPP (ionic cross-linking). For the formation of hydrogels containing megosin, we used different concentrations of chitosan, megosin, and STPP (<a ref-type="table" href="#j_afpuc-2020-0006_tab_001_w2aab3b7c30b1b6b1ab1b2b3Aa">Table 1</a>).</p><table-wrap id="j_afpuc-2020-0006_tab_001_w2aab3b7c30b1b6b1ab1b2b3Aa" position="float"><label>Table 1</label><caption><p>Releasing level of megosin from chitosan hydrogels</p></caption><table rules="all"><thead><tr><th align="center" valign="middle" colspan="3"><bold>Gel composition</bold></th><th align="center" valign="middle" rowspan="2"><bold>Release percentage of megosin from the gel for 7 h</bold></th></tr><tr><th align="center" valign="middle"><bold>Chitosan (%)</bold></th><th align="center" valign="middle"><bold>Megosin (mg)</bold></th><th align="center" valign="middle"><bold>STPP (%)</bold></th></tr></thead><tbody><tr><td align="center" valign="middle">2</td><td align="center" valign="middle">1</td><td align="center" valign="middle">1.4</td><td align="center" valign="middle">20.73 ± 2.33</td></tr><tr><td align="center" valign="middle">2</td><td align="center" valign="middle">2</td><td align="center" valign="middle">1.4</td><td align="center" valign="middle">25.88 ± 1.11</td></tr><tr><td align="center" valign="middle">2</td><td align="center" valign="middle">1</td><td align="center" valign="middle">2.8</td><td align="center" valign="middle"><bold>46.72 ± 2.58</bold></td></tr><tr><td align="center" valign="middle">2</td><td align="center" valign="middle">2</td><td align="center" valign="middle">2.8</td><td align="center" valign="middle">32.93 ± 0.89</td></tr><tr><td align="center" valign="middle">4</td><td align="center" valign="middle">1</td><td align="center" valign="middle">0</td><td align="center" valign="middle"><bold>59.89 ± 1.80</bold></td></tr><tr><td align="center" valign="middle">4</td><td align="center" valign="middle">1</td><td align="center" valign="middle">1.4</td><td align="center" valign="middle"><bold>51.62 ± 1.68</bold></td></tr><tr><td align="center" valign="middle">4</td><td align="center" valign="middle">1</td><td align="center" valign="middle">2.8</td><td align="center" valign="middle"><bold>44.91 ± 1.44</bold></td></tr><tr><td align="center" valign="middle">4</td><td align="center" valign="middle">1</td><td align="center" valign="middle">5.6</td><td align="center" valign="middle">11.96 ± 0.69</td></tr><tr><td align="center" valign="middle">5</td><td align="center" valign="middle">1</td><td align="center" valign="middle">0</td><td align="center" valign="middle">11.07 ± 2.13</td></tr><tr><td align="center" valign="middle">5</td><td align="center" valign="middle">1</td><td align="center" valign="middle">1.4</td><td align="center" valign="middle">6.71 ± 0.667</td></tr></tbody></table></table-wrap><p>The results showed the highest release level of megosin in 4% chitosan solutions without STPP and with 1.4% and 2.8% STPP containing 1 mg of megosin. More than half the amount of megosin was found released in these samples for 7 h. When 5.6% STPP is included, fourfold lower drug amounts were found released. We determined similar low-level drug release in 5% chitosan solutions. Gel samples with 2% chitosan solution resulted in a moderate level of drug release in almost all cases. The exception was observed in a 2% chitosan gel with 2.8% STPP inclusion, in which just less than half the drug amount was found released for 7 h (<a ref-type="table" href="#j_afpuc-2020-0006_tab_001_w2aab3b7c30b1b6b1ab1b2b3Aa">Table 1</a>).</p><p>In terms of release yield, gels with 5% chitosan and 5.6% STPP were found the most retaining, likely due to high viscosity and strong cross-linking (<a ref-type="table" href="#j_afpuc-2020-0006_tab_001_w2aab3b7c30b1b6b1ab1b2b3Aa">Table 1</a>). The kinetics of megosin release from chitosan hydrogel samples for 7 h demonstrated a gradual increase in 4% chitosan solutions (<a ref-type="fig" href="#j_afpuc-2020-0006_fig_002_w2aab3b7c30b1b6b1ab1b2b6Aa">Fig. 2</a>). The process was carried out in conditions mimicking the female body (0.558 mm lactic acid, pH 4.5), For this, a dialysis bag, containing 1 ml of gel, was immersed in a test tube and 5 ml of lactic acid solution was added. After a certain period of time, the solution was taken. In selected solutions, the absorbance was measured at 384 nm, characteristic for megosin. A pre-constructed calibration curve for megosin was used to determine the concentration.</p><figure id="j_afpuc-2020-0006_fig_002_w2aab3b7c30b1b6b1ab1b2b6Aa" position="float" fig-type="figure"><h2>Figure 2</h2><figCaption><p>Kinetics of megosin release from 4% chitosan gel samples</p></figCaption><img xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/j_afpuc-2020-0006_fig_002.jpg" src="https://sciendo-parsed.s3.eu-central-1.amazonaws.com/6470849271e4585e08a9f0af/j_afpuc-2020-0006_fig_002.jpg?X-Amz-Algorithm=AWS4-HMAC-SHA256&amp;X-Amz-Date=20240730T134124Z&amp;X-Amz-SignedHeaders=host&amp;X-Amz-Expires=18000&amp;X-Amz-Credential=AKIA6AP2G7AKP25APDM2%2F20240730%2Feu-central-1%2Fs3%2Faws4_request&amp;X-Amz-Signature=8f985806ad96a1b677c4af7df31826d9e5681244b31cef16af9162f9972654b2" class="mw-100"/></figure><p>In addition to polar groups (NH<sub>2</sub> in chitosan and SO<sub>3</sub>ONa in megosin) attractions, hydrogen bonds among OH- and NH-groups and van der Waals interactions have been shown to contribute to the retention of megosin in its complex with polyvinylpyrrolidone (<a ref-type="bibr" href="#j_afpuc-2020-0006_ref_016_w2aab3b7c30b1b6b1ab2b1c16Aa">Ionov et al., 2009</a>). However, interactions between charged groups likely are the main contributor for the release of the drug in this work, which can be explained by small differences between the non-cross-linked gel and the gel with 1.4% STPP. Moreover, this interaction could lead to higher solubility of megosin in water, which enables its application in biomedicine.</p><p>In this work, we determined the stability of megosin in the obtained gels on the 15th day of formation. For this, the exact amount of the gel was taken and freeze-dried. Megosin was extracted with acetone:water system (3:1, v/v). Further, the obtained samples were analyzed by HPLC (<a ref-type="fig" href="#j_afpuc-2020-0006_fig_003_w2aab3b7c30b1b6b1ab1b2b9Aa">Fig. 3</a>).</p><figure id="j_afpuc-2020-0006_fig_003_w2aab3b7c30b1b6b1ab1b2b9Aa" position="float" fig-type="figure"><h2>Figure 3</h2><figCaption><p>HPLC analysis of megosin in 4% chitosan gel cross-linked with 1.4% STPP</p></figCaption><img xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/j_afpuc-2020-0006_fig_003.jpg" src="https://sciendo-parsed.s3.eu-central-1.amazonaws.com/6470849271e4585e08a9f0af/j_afpuc-2020-0006_fig_003.jpg?X-Amz-Algorithm=AWS4-HMAC-SHA256&amp;X-Amz-Date=20240730T134124Z&amp;X-Amz-SignedHeaders=host&amp;X-Amz-Expires=18000&amp;X-Amz-Credential=AKIA6AP2G7AKP25APDM2%2F20240730%2Feu-central-1%2Fs3%2Faws4_request&amp;X-Amz-Signature=d00b1db0b281f69c3e776e590d75843219f20b56ed16cfc354c9c102bc60f6ef" class="mw-100"/></figure><p>The HPLC analysis of megosin, isolated from chitosan hydrogel cross-linked with 1.4% STPP, demonstrated its stability and partial degradation in the gel for 15 days. The main peak with a retention time 10.351 is attributed to megosin. The peak at 15.617 is possibly the degradation product of megosin. Further research will clarify its structure and activity.</p><p>The IR spectra of megosin, chitosan, and the dried chitosan gel sample containing megosin were obtained (<a ref-type="fig" href="#j_afpuc-2020-0006_fig_004_w2aab3b7c30b1b6b1ab1b2c12Aa">Fig. 4</a>). The structural rearrangement that occurs upon modification of chitosan with STPP is accompanied by changes in the spectra. A low-frequency shift and a noticeable broadening of the absorption bands corresponding to ν (NH) vibrations were observed, which indicates the formation of bonds making chitosan cross-linked via NH<sub>2</sub> group. There is a shift to the low-frequency region of the deformation vibration δ (NH) band, which indicates the involvement of these groups in binding to P<sub>3</sub>O<sub>10</sub><sup>−5</sup> anions. In addition, bands appear at 1217–1214 cm<sup>−1</sup>, corresponding to vibrations of ν (P = O).</p><figure id="j_afpuc-2020-0006_fig_004_w2aab3b7c30b1b6b1ab1b2c12Aa" position="float" fig-type="figure"><h2>Figure 4</h2><figCaption><p>Infrared spectra of chitosan (A), megosin (B), and the dried gel sample on their bases (C)</p></figCaption><img xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/j_afpuc-2020-0006_fig_004.jpg" src="https://sciendo-parsed.s3.eu-central-1.amazonaws.com/6470849271e4585e08a9f0af/j_afpuc-2020-0006_fig_004.jpg?X-Amz-Algorithm=AWS4-HMAC-SHA256&amp;X-Amz-Date=20240730T134124Z&amp;X-Amz-SignedHeaders=host&amp;X-Amz-Expires=18000&amp;X-Amz-Credential=AKIA6AP2G7AKP25APDM2%2F20240730%2Feu-central-1%2Fs3%2Faws4_request&amp;X-Amz-Signature=43056e4a1a4facf425784c35dd1f0cc875d8aa124b45115b0347df6d00969445" class="mw-100"/></figure><p>The possible passage of megosin from the chitosan hydrogel into the blood was studied using compositions with the highest release of megosin: 4% chitosan without STPP, 4% chitosan with 1.4% and 2.8%, and 2% chitosan with 2.8% STPP (all with 1 mg megosin). Each group contained at least five experimental animals. The gel was administered intervaginally to white rats. Quantitative determination of megosin was performed by HPLC. No detectable quantity of megosin, released from chitosan hydrogel to blood samples, was found by HPLC analysis.</p></sec><sec id="j_afpuc-2020-0006_s_004_w2aab3b7c30b1b6b1ab1b3Aa"><div>CONCLUSION</div><p>Thus, we obtained chitosan hydrogels with the antiviral drug megosin. The essential feature of the obtained gel is the ability to swell, mechanical strength, and biodegradation. In addition to the intrinsic properties of chitosan, such as antibacterial and antifungal activity, biocompatibility, and biodegradability, the resulting gels have antiviral properties. Megosin retains its antiviral properties in gels and does not penetrate into the blood. More than half the amount of megosin was found to be released from the gel within 7 h. The use of megosin-containing hydrogel on the basis of chitosan will allow the reduction of the megosin dose and the frequency of the gel so that application of the gel will be more convenient.</p></sec></div>

Chitosan Hydrogel Improves Bioavailability of Megosin

Laboratory of Proteins and Peptides Chemistry

European Pharmaceutical Journal

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

{"article-title":"Chitosan Hydrogel Improves Bioavailability of Megosin"}

BackgroundThe aim of this study was to obtain chitosan hydrogels containing megosin, an antiviral medicinal substance, to prolong its bioavailability. Megosin...

Chitosan Hydrogel Improves Bioavailability of Megosin

Article Category: Original Paper

Publié en ligne: 18 nov. 2020

Pages: 1 - 6

Reçu: 10 mai 2019

Accepté: 14 janv. 2020

DOI: https://doi.org/10.2478/afpuc-2020-0006

Mots clés
Chitosan hydrogel, megosin, vaginal herpes

© 2019 Sultanova E. M. et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Chitosan Hydrogel Improves Bioavailability of Megosin

Article Category: Original Paper

Publié en ligne: 18 nov. 2020

Pages: 1 - 6

Reçu: 10 mai 2019

Accepté: 14 janv. 2020

DOI: https://doi.org/10.2478/afpuc-2020-0006

Mots clésChitosan hydrogel, megosin, vaginal herpes

© 2019 Sultanova E. M. et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Mots clés
Chitosan hydrogel, megosin, vaginal herpes