Clotrimazole-Loaded Borneol-Based In Situ Forming Gel as Oral Sprays for Oropharyngeal Candidiasis Therapy

Abstract

Oral candidiasis encompasses fungal infections of the tongue and other oral mucosal sites with fungal overgrowth and its invasion of superficial oral tissues. Borneol was assessed in this research as the matrix-forming agent of clotrimazole-loaded in situ forming gel (ISG) comprising clove oil as the co-active agent and N-methyl pyrrolidone (NMP) as a solvent. Their physicochemical properties, including pH, density, viscosity, surface tension, contact angle, water tolerance, gel formation, and drug release/permeation, were determined. Their antimicrobial activities were tested using agar cup diffusion. The pH values of clotrimazole-loaded borneol-based ISGs were in the range of 5.59–6.61, which are close to the pH of 6.8 of saliva. Increasing the borneol content in the formulation slightly decreased the density, surface tension, water tolerance, and spray angle but increased the viscosity and gel formation. The borneol matrix formation from NMP removal promoted a significantly (p < 0.05) higher contact angle of the borneol-loaded ISGs on agarose gel and porcine buccal mucosa than those of all borneol-free solutions. Clotrimazole-loaded ISG containing 40% borneol demonstrated appropriate physicochemical properties and rapid gel formation at microscopic and macroscopic levels. In addition, it prolonged drug release with a maximum flux of 370 µg·cm−2 at 2 days. The borneol matrix generated from this ISG obsentively controlled the drug penetration through the porcine buccal membrane. Most clotrimazole amounts still remained in formulation at the donor part and then the buccal membrane and receiving medium, repectively. Therefore, the borneol matrix extended the drug release and penetration through the buccal membrane efficiently. Some accumulated clotrimazole in tissue should exhibit its potential antifugal activity against microbes invading the host tissue. The other predominant drug release into the saliva of the oral cavity should influence the pathogen of oropharyngeal candidiasis. Clotrimazole-loaded ISG demonstrated efficacious inhibition of growth against S. aureus, E. coli, C. albicans, C. krusei, C. Lusitaniae, and C. tropicalis. Consequently, the clotrimazole-loaded ISG exhibited great potential as a drug delivery system for oropharyngeal candidiasis treatment by localized spraying.

Lincomycin HCl-Loaded Borneol-Based In Situ Gel for Periodontitis Treatment

“…The contact angle of NMP on the glass slide was significantly ( p < 0.05) higher than those of NB40 and drug-loaded ISGs, respectively, indicating that the addition of both borneol and lincomycin decreased the hydrophilicity of the formulation and declined the contact angle. For borneol, it is a lipophilic bicyclic monoterpene alcohol (log K o/w = 2.85) [ 38 ]. The enhancement of viscosity owing to the higher drug loading decreased the speadability and slightly enhanced the contact angle on the glass surface.…”

Development and Characterization of New Miconazole-Based Microemulsions for Buccal Delivery by Implementing a Full Factorial Design Modeling

“…Over time, it was proven a safe handle and incorporation of active pharmaceutical ingredients (API) for the treatment of oral candidiasis in various buccal dosage forms like suspensions [ 15 ], medical mouthwashes [ 16 , 17 ], gels and in situ forming gels [ 18 , 19 ], varnishes and troches [ 20 ], mucoadhesive tablets [ 21 ], and versatile hydrogels and polymeric films [ 22 , 23 , 24 ]. Furthermore, novel nanotherapeutic systems proposed progress in increasing API bioavailability and therapeutic efficacy [ 25 ].…”