Comparison of Rheological, Drug Release, and Mucoadhesive Characteristics upon Storage between Hydrogels with Unmodified or Beta-Glycerophosphate-Crosslinked Chitosan

<div>Box-plot graphs presenting mucoadhesive properties: (a) maximum force of detachment (<svg height="11.9316pt" id="M31" style="vertical-align:-3.2957pt" version="1.1" viewbox="-0.0498162 -8.6359 23.5035 11.9316" width="23.5035pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M584 650H137L131 622C214 614 217 612 200 521L125 127C109 41 101 35 23 28L17 0H288L294 28C201 35 193 42 209 128L242 309H348C440 309 442 300 443 226H471L510 422H482C452 354 449 348 357 348H251L295 575C302 609 304 615 338 615H426C502 615 517 604 526 581C534 560 536 524 537 492L565 494C574 554 583 631 584 650Z" id="g113-71"></path></g><g transform="matrix(.0091,0,0,-0.0091,6.786,3.132)"><path d="M810 0V30C751 35 744 40 744 106V296C744 396 694 451 614 451C583 451 558 438 537 425C512 409 485 391 454 368C434 420 390 451 342 451C309 451 285 439 260 424C228 405 206 387 185 372V453C141 434 90 421 43 413V386C102 378 105 373 105 309V106C105 41 96 35 29 30V0H243V30C194 35 185 41 185 106V335C216 360 256 389 297 389C357 389 384 348 384 275V106C384 41 374 35 312 30V0H530V30C475 35 465 41 465 104V294C465 313 464 324 463 336C502 367 539 389 576 389C637 389 663 346 663 274V109C663 41 653 35 593 30V0H810Z" id="g58-107"></path></g><g transform="matrix(.0091,0,0,-0.0091,14.348,3.132)"><path d="M442 39L431 68C420 63 406 57 394 57C377 57 359 71 359 118V301C359 353 349 393 314 424C291 443 261 451 230 451C171 438 107 401 79 381C59 366 46 355 46 340C46 316 72 295 91 295C106 295 117 303 122 319C131 350 139 371 152 384C163 397 178 404 197 404C246 404 281 365 281 293V278C260 262 186 232 124 213C69 194 41 161 41 112C41 47 92 -12 163 -12C195 -12 243 25 283 51C288 35 293 22 308 7C319 -4 339 -12 354 -12L442 39ZM281 87C262 68 226 51 199 51C169 51 129 74 129 126C129 162 151 181 190 198C211 208 259 229 281 240V87Z" id="g58-95"></path></g><g transform="matrix(.0091,0,0,-0.0091,18.434,3.132)"><path d="M482 0V30C420 38 407 48 370 103L273 248C308 299 331 332 352 357C387 397 401 404 463 409V439H277V409C318 405 324 400 307 369C290 337 270 307 251 279L194 367C175 396 180 402 220 409V439H18V409C74 401 87 395 117 349L204 213C173 168 147 130 119 95C78 46 67 38 5 30V0H195V30C144 38 143 47 162 79C181 112 202 149 225 181L297 70C314 43 307 35 264 30V0H482Z" id="g58-118"></path></g></svg>) and (b) work of adhesion (<svg height="11.9316pt" id="M32" style="vertical-align:-3.2957pt" version="1.1" viewbox="-0.0498162 -8.6359 20.4031 11.9316" width="20.4031pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M962 650H739L732 622L760 619C812 613 819 604 798 552C760 457 671 267 606 131H604L511 638H480L237 131H233L183 554C177 607 183 614 226 619L248 622L257 650H24L17 622C88 615 92 611 103 524L173 -11H203L450 491H453L543 -11H575L839 529C882 609 886 613 953 622L962 650Z" id="g113-88"></path></g><g transform="matrix(.0091,0,0,-0.0091,10.777,3.132)"><path d="M442 39L431 68C420 63 406 57 394 57C377 57 359 71 359 118V301C359 353 349 393 314 424C291 443 261 451 230 451C171 438 107 401 79 381C59 366 46 355 46 340C46 316 72 295 91 295C106 295 117 303 122 319C131 350 139 371 152 384C163 397 178 404 197 404C246 404 281 365 281 293V278C260 262 186 232 124 213C69 194 41 161 41 112C41 47 92 -12 163 -12C195 -12 243 25 283 51C288 35 293 22 308 7C319 -4 339 -12 354 -12L442 39ZM281 87C262 68 226 51 199 51C169 51 129 74 129 126C129 162 151 181 190 198C211 208 259 229 281 240V87Z" id="g58-95"></path></g><g transform="matrix(.0091,0,0,-0.0091,14.836,3.132)"><path d="M526 56L493 58C457 61 448 68 448 119V710C411 697 344 682 288 675V646C362 641 367 639 367 573V439C344 448 315 451 300 451C164 451 40 342 40 202C40 61 147 -12 227 -12C239 -12 266 -7 305 16L367 53V-12C427 10 505 21 526 26V56ZM367 88C342 69 306 54 271 54C207 54 133 111 133 229C133 373 219 409 264 409C301 409 342 394 367 359V88Z" id="g58-98"></path></g></svg>) of hydrogels with unmodified CS (F1, F2) or with bGP-crosslinked CS (F3, F4) directly after preparation (<svg height="11.1049pt" id="M33" style="vertical-align:-3.29108pt" version="1.1" viewbox="-0.0498162 -7.81382 9.43046 11.1049" width="9.43046pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M324 430H196L233 583L223 592L145 529L120 430H54L29 396L31 388H111L56 126C33 15 54 -12 77 -12C137 -12 214 57 250 95L233 119C208 92 155 59 138 59C126 59 120 70 131 125L186 390L298 394L324 430Z" id="g113-117"></path></g><g transform="matrix(.0091,0,0,-0.0091,4.368,3.132)"><path d="M245 635C92 635 37 457 37 312C37 149 91 -12 244 -12C395 -12 449 166 449 312C449 469 395 635 245 635ZM243 598C332 598 358 454 358 312C358 173 334 26 245 26C158 26 128 174 128 313S152 598 243 598Z" id="g50-49"></path></g></svg>) and upon 1-month (<svg height="10.9953pt" id="M34" style="vertical-align:-3.18148pt" version="1.1" viewbox="-0.0498162 -7.81382 9.43046 10.9953" width="9.43046pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M324 430H196L233 583L223 592L145 529L120 430H54L29 396L31 388H111L56 126C33 15 54 -12 77 -12C137 -12 214 57 250 95L233 119C208 92 155 59 138 59C126 59 120 70 131 125L186 390L298 394L324 430Z" id="g113-117"></path></g><g transform="matrix(.0091,0,0,-0.0091,4.368,3.132)"><path d="M389 0V32C297 38 291 46 291 118V635C234 613 175 595 109 583V556L161 554C203 552 207 547 207 497V118C207 46 201 38 110 32V0H389Z" id="g50-50"></path></g></svg>), 3-month (<svg height="11.1049pt" id="M35" style="vertical-align:-3.29108pt" version="1.1" viewbox="-0.0498162 -7.81382 9.43046 11.1049" width="9.43046pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M324 430H196L233 583L223 592L145 529L120 430H54L29 396L31 388H111L56 126C33 15 54 -12 77 -12C137 -12 214 57 250 95L233 119C208 92 155 59 138 59C126 59 120 70 131 125L186 390L298 394L324 430Z" id="g113-117"></path></g><g transform="matrix(.0091,0,0,-0.0091,4.368,3.132)"><path d="M290 377C321 398 342 415 358 430C378 450 389 473 389 502C389 578 329 635 238 635H237C184 635 137 610 109 578L64 515L88 493C112 529 154 573 208 573S303 542 303 482C303 409 233 370 141 341L149 308C165 313 190 319 215 319C272 319 341 283 341 193C342 98 292 43 222 43C163 43 122 72 96 94C88 101 79 100 70 94C61 87 47 73 46 60C44 47 48 37 62 23C76 10 118 -12 165 -12C238 -12 430 62 430 223C430 297 379 359 290 375V377Z" id="g50-52"></path></g></svg>), or 6-month (<svg height="11.1049pt" id="M36" style="vertical-align:-3.29108pt" version="1.1" viewbox="-0.0498162 -7.81382 9.43046 11.1049" width="9.43046pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M324 430H196L233 583L223 592L145 529L120 430H54L29 396L31 388H111L56 126C33 15 54 -12 77 -12C137 -12 214 57 250 95L233 119C208 92 155 59 138 59C126 59 120 70 131 125L186 390L298 394L324 430Z" id="g113-117"></path></g><g transform="matrix(.0091,0,0,-0.0091,4.368,3.132)"><path d="M141 347C171 480 264 541 327 570C364 587 403 599 436 605L429 641C389 634 339 622 300 609C191 570 37 458 37 239C37 86 126 -12 245 -12C367 -12 454 89 454 210C454 314 380 397 272 397C252 397 230 390 208 380L141 347ZM231 338C323 338 366 257 366 174C366 108 340 27 263 27C180 27 129 123 129 244C129 268 130 292 135 310C158 323 193 338 231 338Z" id="g50-55"></path></g></svg>) storage at ambient, accelerated, and refrigerated conditions (<span class="nowrap"><svg height="8.55521pt" id="M37" style="vertical-align:-0.2063904pt" version="1.1" viewbox="-0.0498162 -8.34882 27.8368 8.55521" width="27.8368pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M495 86L479 114C446 82 419 66 409 66C401 66 401 72 406 97C420 166 436 231 453 297C489 435 454 448 428 448C406 448 384 439 354 422C305 394 222 327 161 247H159L183 345C200 415 194 448 173 448C143 448 82 410 23 351L38 325C64 349 95 371 105 371C111 371 116 365 109 336L25 -4L31 -12C50 -4 77 3 107 9C119 69 132 122 145 168C197 254 321 381 370 381C387 381 393 374 378 305L329 95C309 17 320 -12 345 -12C372 -12 430 19 495 86Z" id="g113-111"></path></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z" id="g117-34"></path></g><g transform="matrix(.013,0,0,-0.013,21.421,0)"><path d="M137 343C167 482 260 545 321 574C357 591 397 603 429 609L423 641C382 634 335 622 295 608C189 570 37 457 37 238C37 84 125 -12 242 -12C362 -12 447 89 447 209C447 311 374 393 267 393C247 393 226 386 204 376L137 343ZM227 337C318 337 361 256 361 173C361 105 336 22 258 22C176 22 126 120 126 240C126 266 127 291 132 310C155 323 189 337 227 337Z" id="g113-55"></path></g></svg>,</span> median); C: control, mucoadhesive vaginal gel Replens™.</div>

International Journal of Polymer Science

fig4

Figure 4

Figure 4: Comparison of Rheological, Drug Release, and Mucoadhesive Characteristics upon Storage between Hydrogels with Unmodified or Beta-Glycerophosphate-Crosslinked Chitosan 

Figure 4 | Comparison of Rheological, Drug Release, and Mucoadhesive Characteristics upon Storage between Hydrogels with Unmodified or Beta-Glycerophosphate-Crosslinked Chitosan 