Development of Itraconazole-Loaded Polymeric Nanoparticle Dermal Gel for Enhanced Antifungal Efficacy

Abstract

Fungal infection of the skin is one of the most common dermatological diseases in the world. Gel formulations are among the most suitable dosage forms for topical use to treat cutaneous infection. Nanotechnology is a promising approach to penetrate the deeper skin layers and enhance permeability of itraconazole (ITZ) through the stratum corneum. ITZ-loaded nanoparticles (ITZ NPs) were fabricated using the evaporation emulsion method, followed by incorporation of NPs into gel using Carbopol 934 as the gel-forming excipient. The physical properties, in vitro release, ex vivo permeation studies, and antifungal activity of ITZ NP gel were characterized. ITZ NPs were almost spherical in shape with colloidal sizes in the range of 200 nm. The drug encapsulation efficiency was 98.79 ± 1.24 %. ITZ NP gel demonstrated a sustained ex vivo permeation of ITZ over 24 h through excised rat skin and a higher drug penetrating capacity than that of a gel containing ITZ-saturated suspension. The in vitro antifungal activity of the ITZ-loaded NP incorporated gel was better than that of ITZ dispersion. Incorporation of the ITZ-loaded nanosystem into gel has the potential to enhance antifungal activity through transdermal drug delivery.

Assessment of antifungal efficacy of itraconazole loaded aspasomal cream: comparative clinical study

“…Such high doses over long durations inevitably result in the reported adverse reactions or toxicity. Also, when administered topically to the eye, it was applied at concentration of 1% (Ho et al., 2020 ). However, this is not the case in our study.…”

“…It is well-documented that high molecular weight drugs >500 Da possess poor permeation across the stratum corneum layer of the skin. Despite its high molecular weight, however, high lipophilicity of ITZ enables it to accumulate in the keratin layer and reside in skin (Ho et al., 2020 ). The great affinity of azole drugs including ITZ to keratin layer serving as a reservoir for drugs with negligible deposition into epidermis and dermis was stated earlier (Jukanti et al., 2011 ; El-Sheridy et al., 2019 ; Aboul-Einien et al., 2020 ).…”

Polymeric Nanoparticles as Tunable Nanocarriers for Targeted Delivery of Drugs to Skin Tissues for Treatment of Topical Skin Diseases

“…The superior antifungal activity of TB-loaded PNPs was attributed to a higher skin permeation and retention (approximately 78%) into the skin layers compared to commercial cream and gel formulations [ 30 ]. Similarly, Ho et al [ 46 ] encapsulated itraconazole (ITZ) into ethylcellulose (EC)-NPs and then incorporated them into a topical gel formulation with semisolid consistency. A comparative analysis on rat epidermis revealed an approximately 20-fold higher permeability and 7-fold higher skin retention of ITZ-EC-NPs released from the topically applied gel compared to ITZ suspension gel.…”

Beneath the Skin: A Review of Current Trends and Future Prospects of Transdermal Drug Delivery Systems

“…Several studies have reported the use of NPs as TDD systems. For instance, Hoang Nhan Ho et al [182] revealed that a prolonged release profile and good penetration of itraconazole through mouse skin were achieved using polymeric NPs with col- Organic (polymeric) NPs are fabricated by the polymerization and crosslinking of biodegradable polymers [175,176]. Such polymeric nanoparticles are often fabricated by inducing the "self-assembly" of the polymer-a process by which the polymer is forced to assume a coiled, particulate form as opposed to an uncoiled chain conformation.…”

“…Several studies have reported the use of NPs as TDD systems. For instance, Hoang Nhan Ho et al [182] revealed that a prolonged release profile and good penetration of itraconazole through mouse skin were achieved using polymeric NPs with colloidal sizes in the range of 200 nm. In addition, they found that the incorporation of itraconazole-loaded NPs into a gel formulation for TDD has the potential to improve antifungal activity with respect to the conventional gel.…”