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Tumor Discovery A comprehensive review of bexarotene

management and therapy of CTCL. In January 2000, In 2019, Zhang et al. revealed that the aerosol
Ligand Pharmaceuticals launched this spectacular drug formulations of bexarotene restrain major subtypes of lung
as Targretin capsules in the United States. The company malignant growth in mice by inhibiting cell proliferation
introduced the drug as a salvage therapy for patients and increasing apoptosis. This methodology holds
diagnosed with CTCL. The new drug application for significant promise for improving lung cancer prevention,
Targretin capsules and Targretin gel was filed in June especially for high-risk populations such as smokers .
[57]
1999 and December 1999, respectively. Subsequently, the In 2018, Vasile et al. uncovered the advancement of new
company marketed the Targretin capsules worldwide . bexarotene-stacked mesoporous silica frameworks for
[52]
The FDA also approved the 1% gel of Targretin for treating topical pharmaceutical administration. Bexarotene, a
patients with refractory or persistent early-stage CTCL . highly toxic and sparingly water-soluble compound, often
[53]
In 1999, bexarotene was designated as an orphan drug. In exhibits low bioavailability in conventional pharmaceutical
2006, Eisai Co., Ltd. acquired the rights for formulation formulations. However, through adsorption on dynamic
development and commercialization of bexarotene under habitats in a non-crystalline state, these silica amino-
the brand name Targretin ®[54] . In addition, pharmaceutical functionalized frameworks played a crucial role in
companies such as Bausch Health and Cardinal Health have enhancing the drug’s solubility and bioavailability .
[58]
also been involved in marketing bexarotene. The marketed Similarly, in 2018, Lee et al. developed a lipid-based

formulations of bexarotene are tabulated in Table 1. solution and suspension of bexarotene to predict its oral
bioavailability. They found that liver microsomal stability
7. Research conducted on formulation was crucial for achieving better oral bioavailability .
[59]
development of bexarotene In addition, nanocrystals of bexarotene considerably
Bexarotene has shown remarkable effectiveness in treating enhanced the in vitro cytotoxicity by arresting the G1
various disorders. As researchers strive to enhance its phase of the cell cycle and inducing programmed cell death
therapeutic potential, efforts are being made to overcome of A549 cells, establishing its usefulness in the treatment of
[25]
its drawbacks, such as poor solubility and bioavailability. lung cancer .
Multiple techniques, including nanocarriers, solid In 2014, Chen et al. revealed that they utilized a
dispersions, and nanoparticles, have been employed to symmetrical structure to screen the ideal stabilizers and
address these challenges . For instance, the formulation employed precipitation and microfluidization strategies to
[6]
of bexarotene-loaded liposomal gel has successfully obtain the ideal nanocrystals of bexarotene. Bioavailability
conquered the issues of low solubility and permeability, was expanded as a result of the avoidance of first-pass
effectively treating psoriasis . In another study conducted metabolism . Moreover, in the same year, nanocrystals
[55]
[6]
by de Oliveira et al. in 2020, PEGylated polycaprolactone were formulated, demonstrating prominent improvements
(PCL) bexarotene nanoparticles were developed to in the disintegration and retention of bexarotene, and as a
overcome local enzymatic degradation and rapid nasal result, GIT assimilation was enhanced .
[1]
mucociliary clearance. These nanoparticles demonstrated
enhanced epithelial permeation and facilitated efficient In 2022, Singh et al. prepared solid dispersion using
drug delivery to the brain through the intranasal route . both natural and synthetic polymers and found that
[56]
both polymers enhanced the solubility of bexarotene.
Table 1. Marketed formulations of bexarotene However, the solid dispersion prepared with a natural
polymer such as locust bean gum showed amorphous
No Name Dosage Route Company and porous characteristics. The study suggests that this
1. Targretin ® Capsule Oral Ligand Pharmaceuticals, formulation is a suitable candidate for third-generation
USA (3D) solid dispersion and 3D tablet printing, particularly
2. Targretin ® Gel Topical Ligand Pharmaceuticals, for personalized medicine purposes .
[60]
USA
3. Targretin ® Capsule Oral Eisai Co., Ltd., Tokyo In 2022, Xiao et al. conducted a study where they
4. Targretin ® Capsule Oral Eisai Co., Ltd., Tokyo collected a balanced dataset and trained the CocrystalGCN
(liquid-filled) model. The model demonstrated favorable performance
5. Targretin ® Gel Topical Eisai Co., Ltd., Tokyo with AUC, accuracy, precision, and recall values of 0.866,
0.811, 0.802, and 0.830, respectively. Utilizing the model,
6. Targretin ® Capsule Oral Bausch Health, USA four new bexarotene cocrystals were obtained through
(liquid-filled)
7. Targretin ® Gel Topical Bausch Health, USA virtual and experimental screening. These cocrystals
exhibited superior solubility and dissolution compared to
8. Targretin ® Capsule Oral Cardinal Health, USA the parent bexarotene in buffer solutions. Pharmacokinetic

Volume 2 Issue 2 (2023) 7 https://doi.org/10.36922/td.0436