Several chitosan-containing products were approved by the US Food and Drug Administration. Ĭhitosan polymers such as carboxymethyl chitosan (CMC) are suitable for coating nanoparticles by electrostatic interaction and can enhance the physicochemical properties of nanoparticles. Kim and coworkers suggested that loaded AMSN with brimonidine can increase the ocular bioavailability of the drug by increasing the residence time at the preocular surface and controlling the release of the drug. Furthermore, the drug-loaded AMSN could be released in a controlled manner from the particles to maintain a concentration gradient, which improves the drug permeation through the corneal barriers. The hydroxyl groups could form hydrogen bonds with the mucin and the positive charge of the amino groups in the AMSN could also form an ionic complex with the negatively charged groups in mucin. As AMSN has two functional groups, hydroxyl and amine groups, the nanoparticles would be mucoadhesive. (2018) proposed an amino-functionalized mesoporous silica nanoparticle (AMSN) for the ocular delivery of brimonidine for glaucoma. Mucoadhesive materials need to possess a functional group that forms a bond with the mucin. By this approach, many researchers tried nano- or micro-particles made of mucoadhesive polymers such as poly (ethylene glycol), poly (acrylic acid), chitosan, and sodium carboxymethylcellulose for ocular drug delivery. Increasing the residence time of the particles and slowly releasing the loaded drug would improve the ocular bioavailability of the drug. Mucoadhesive particles can be better attached to the mucin on the ocular surface, which increases the residence time in the preocular region. Particles with a mucoadhesive property have been extensively investigated as carriers of ocular drug delivery. Usually, 5-FU eye drops are prepared as an extemporaneous preparation and the solution would be stable for only 7 days. Long-term follow-up is necessary for these patients as the lesions may recur after the therapy. However, the lesion may recur and retreatment is required with an excisional biopsy. The treatment regime for corneal and conjunctival intraepithelial neoplasia, squamous cell carcinoma, and malignant melanoma of conjunctiva can be a pulse ocular doses of 1% 5-FU four times a day for 4 days, for several treatment cycles at monthly intervals. ![]() The ocular solution of 5-FU can be used for conjunctival/corneal squamous cell carcinoma. Thus, the 5-FU loaded in AMSN-CMC gel could be used as a topical formulation for the treatment of ocular cancer.ĥ-Fluorouracil (5-FU) is commonly used to treat many cancer diseases including epithelial cancers. AMSN-CMC-FU gel and AMSN-FU gel were “minimally irritating” to rabbit eyes but showed minimal eye irritation potency in comparison to the 5 FU gel. AMSN-CMC-FU showed 1.52- and 6.14-fold higher AUC0-inf in comparison to AMSN-FU and 5-FU gel, respectively. Higher bioavailability of AMSN-FU and AMSN-CMC-FU gel formulations was found compared to 5-FU gel in the ocular pharmacokinetic study with superior pharmacokinetics parameters of AMSN-CMC-FU gel. AMSN-CMC-FU initially exhibited a 2.45-fold increase in transcorneal flux and apparent permeation of 5-FU compared to 5-FU gel, indicating a better corneal permeation. ![]() Release profiles showed 100% of the drug was released from the 5-FU gel within 4 h, while AMSN-FU gel released 20.8% of the drug and AMSN-CMC-FU gel released around 55.6% after 4 h. In addition, TGA, FTIR, and PXRD confirmed the drug loading inside the AMSN-CMC. NMR spectra confirmed the coating of AMSN with the CMC layer. The optimum formulation of AMSN-CMC-FU was found to be nanoparticles with a particle size of 249.4 nm with a polydispersity of 0.429, encapsulation efficiency of 25.8 ± 5.8%, and drug loading capacity of 5.2 ± 1.2%. Eye irritation and ocular pharmacokinetic studies from gel formulations were evaluated in rabbit eyes. The transcorneal permeabilities of 5-FU from AMNS-FU and AMSN-CMC-FU gel formulations were estimated through excised goat cornea and compared to that of 5-FU gel formulation. The mucoadhesion ability of the prepared nanoparticles was tested using the particle method by evaluating the change in zeta potential. In vitro release was conducted through a dialysis membrane in PBS (pH 7.4) using modified Vertical Franz diffusion cells. Physicochemical characterizations were performed by NMR, TGA, FTIR, and PXRD. ![]() The drug encapsulation and loading were determined by the indirect method using HPLC. Particle characterization was performed by the DLS technique (Zeta-Sizer), and structural morphology was examined by SEM and TEM. This study investigates the development of topically applied non-invasive amino-functionalized silica nanoparticles (AMSN) and O-Carboxymethyl chitosan-coated AMSN (AMSN-CMC) for ocular delivery of 5-Fluorouracil (5-FU).
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