Chitosan hydrogels incorporating colloids for sustained drug delivery.

TLDR: The main objective of this review is to report the many existing complex systems composed of CS hydrogels embedding different types of colloids used as drug delivery devices to delay the release of drugs.

About: This article is published in Carbohydrate Polymers.The article was published on 2022-01-01 and is currently open access. It has received 33 citations till now. The article focuses on the topics: Self-healing hydrogels & Drug delivery.

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Figure 5. Influence of the EDAC crosslinking agent concentration on the cumulated release 309 (% of total initially incorporated drug) of BTB incorporated into PC liposomes embedded in a 310 CS hydrogel (A) without EDAC, (B1) with 5 mg EDAC, (B2) 10 mg EDAC, (B3) 20 mg 311 EDAC, (B4) 30 mg EDAC. These release profiles were performed in a phosphate buffer at 312 pH = 7.4 The C curve is representative of the release of BTB from free liposomes (Rao & 313 Alamelu, 1992) 314 315 More recently, a sustained release of calcein over more than 20 days when this water-soluble 316 molecule was incorporated into Phospholipon®-90G liposomes, themselves embedded in 317 CS/gelatin chemical hydrogels. Hydrogels are crosslinked with two different crosslinking 318 agents: glutaraldehyde and sodium sulphate or sodium triphosphate (Ciobanu et al., 2014). In 319 this work, a significant burst effect when calcein was directly incorporated into the hydrogel 320 has been observed. On the contrary, the incorporation of calcein into liposomes (calcein-loaded 321 liposomes incorporated before the CS gelation process) creates a second diffusion barrier and 322 delayed the release of calcein throughout the final assembly. Similar results have been obtained 323 with chemical CS/gelatin hydrogels, crosslinked by glutaraldehyde or sodium tripolyphosphate, 324 incorporating Phospholipon®-90G liposomes (also incorporating calcein) (Paun et al., 2016). 325 An assembly composed of CS hydrogel and Phospholipon®-90G liposomes incorporating 326 calcein has also been elaborated (Popa et al., 2017). These hydrogels were physically 327 crosslinked with the addition of tannic acid. The ability of this assembly to remove the burst 328 release phenomenon, with a sustained release of calcein over few days (less than 10% of 329 initially incorporated calcein were released after 10 days, Figure 6 right versus Figure 6 left 330

Figure 8. Schematic representation of the preparation of « doxorubicin-loaded CS chemical 521 hydrogel/paclitaxel-loaded-PEO-PPO-PEO micelles » by Zhao et al. (Zhao et al., 2011) 522 It has been shown that this « doxorubicin-loaded CS chemical hydrogel/paclitaxel-loaded-523 PEO-PPO-PEO micelles » assembly can delay the in vitro release of these two drugs over 2 524 weeks. The release of doxorubicin seemed to be more influenced than paclitaxel by its 525 incorporation rate and the crosslinker content. A value of pH close to 6.8 increases the release 526

Table 1. Nature and diameters of microparticles, nature of drugs inserted in microparticles of 226 « CS hydrogel/microparticles » assemblies for the controlled delivery of drugs agents used in 227 different biomedical applications 228

Figure 2. Confocal micrograph of gelatin microparticles in chitosan scaffold (Park et al., 102 2009) 103

Figure 7. In vitro cumulative release (% of total initially incorporated drug, in PBS at 37°C) 386 of free CF (triangles), or CF incorporated into 100 nm (circles) or 280 nm (squares) 387 PC/cholesterol liposomes (Ruel-Gariépy et al., 2002) 388 389 In ophthalmic applications, a too small amount of drugs reaching the injury site (such as 390 cornea) is often deplored, partially due to the tear production. Patients thus need repeated drug 391 administrations for an efficient treatment. Moreover, the cornea epithelial membrane represents 392 a barrier to the drug diffusion across the eye (Kaur & Kanwar, 2002). To solve this issue, 393 ofloxacin antibiotic has been incorporated into multilamellar PC liposomes (obtained by the 394 thin film hydration method or inverse phase evaporation) embedded into thermosensitive 395 CS/GP physical hydrogels (Hosny, 2009). Ofloxacin incorporation rates into liposomes were 396 found to be highly variable (between 13 and 65%) depending on the preparation method of 397 liposomes, and their lipid composition (e.g., the lipid charge nature). For example, 398 incorporation rates were higher for liposomes obtained by thin film evaporation than those 399 obtained by inverse phase evaporation (with same lipids and composition). With the liposome 400 suspension, ofloxacin diffusion across the cornea was multiplied by 5 (versus an aqueous 401 solution of ofloxacin). This could be explained by attractive interactions between anionic 402 cornea and PC liposomes. Moreover, a significant increase in ofloxacin diffusion was even 403 more observed when liposomes were embedded in CS/GP hydrogels (multiplied by 7 versus 404 the free ofloxacin solution). Finally, it was demonstrated that the mucoadhesive properties of 405 CS makes the interactions between liposomes and transcorneal membrane easier. 406

Table 2. Nature and diameters of nanoparticles, nature of drugs inserted in nanoparticles of « 279 CS hydrogel/nanoparticles » assemblies for the controlled delivery of drugs used in different 280 biomedical applications 281