Improved Water Solubility Research Articles

Natural gambogic acid-tuned self-assembly of nanodrugs towards synergistic chemophototherapy against breast cancer.

Gambogic acid (GA) as a naturally derived chemotherapeutic agent is of increasing interest for antitumor therapy. However, current research mainly focuses on improving the pharmacological properties to overcome the shortcomings in clinical applications or as a synergistic anticancer agent in combination with chemotherapy and chemophototherapy. Yet, the material properties of GA (e.g., self-assembly) are often neglected. Herein, we validated the self-assembly function of GA and its huge potential as a single-component active carrier for synergistic delivery using pyropheophorbide-a (PPa) as a drug model. The results showed that self-assembled GA drives the formation of nano-GA/PPa mainly through noncovalent interactions such as π-π stacking, hydrophobic interactions, and hydrogen bonding. Additionally, although no significant differences in cytotoxicity were found between the individual in vitro chemotherapy and combined chemophototherapy, the as-prepared nano-GA/PPa exhibits remarkably improved water solubility and multiple favorable therapeutic features, leading to a prominent in vivo photochemotherapy efficiency of 89.3% inhibition rate with reduced hepatotoxicity of GA. This work highlights the potential of self-assembled GA as a drug delivery carrier for synergistic biomedical applications.

Synthesis and biological evaluation of the novel chrysin prodrug for non-alcoholic fatty liver disease treatment.

Background: Chrysin (5,7-dihydroxyflavone) is a natural flavonoid that has been reported as a potential treatment for non-alcoholic fatty liver disease (NAFLD). However, extensive phase II metabolism and poor aqueous solubility led to a decrease in the chrysin concentration in the blood after oral administration, limiting its pharmacological development in vivo. Methods: In the present study, we synthesized a novel chrysin derivative prodrug (C-1) to address this issue. We introduced a hydrophilic prodrug group at the 7-position hydroxyl group, which is prone to phase II metabolism, to improve water solubility and mask the metabolic site. Further, we evaluated the ameliorative effects of C-1 on NAFLD in vitro and in vivo by NAFLD model cells and db/db mice. Results: In vitro studies indicated that C-1 has the ability to ameliorate lipid accumulation, cellular damage, and oxidative stress in NAFLD model cells. In vivo experiments showed that oral administration of C-1 at a high dose (69.3mg/kg) effectively ameliorated hyperlipidemia and liver injury and reduced body weight and liver weight in db/db mice, in addition to alleviating insulin resistance. Proteomic analysis showed that C-1 altered the protein expression profile in the liver and particularly improved the expression of proteins associated with catabolism and metabolism. Furthermore, in our preliminary pharmacokinetic study, C-1 showed favorable pharmacokinetic properties and significantly improved the oral bioavailability of chrysin. Conclusion: Our data demonstrated that C-1 may be a promising agent for NAFLD therapy.

Visualization of the Ferroptosis in Atherosclerotic Plaques with Nanoprobe Engineered by Macrophage Cell Membranes.

Atherosclerosis (AS) is the root cause of cardiovascular diseases. Ferroptosis is characterized by highly iron-dependent lipid peroxidation and has been reported to play an important role in the pathogenesis of AS. Visualization of the ferroptosis process in atherosclerotic plaques is of great importance for diagnosing and treating AS. In this work, the rationally designed fluorescent probe FAS1 exhibited excellent advantages including large Stokes shift, sensitivity to environmental viscosity, good photostability, and improved water solubility. It also could co-locate with commercial lipid droplets (LDs) probes (BODIPY 493/503) well in RAW264.7 cells treated by the ferroptosis inducer. After self-assembly into nanoparticles and then encapsulation with macrophage membranes, the engineered FAS1@MM NPs could successfully target the atherosclerotic plaques in Western diet-induced apolipoprotein E knockout (ApoE-/-) mice and reveal the association of ferroptosis with AS through fluorescence imaging in vivo. This study may provide additional insights into the roles of ferroptosis in the diagnosis and treatment of AS.

Maduramicin-guided nanotherapy: A polymeric micelles for targeted drug delivery in canine mammary tumors

Canine mammary tumors (CMT) can severely compromise the life quality of the affected dogs through local recurrence, distant metastases and ultimately succumb to death. Recently, more attention has been given to the potential antimetastatic effect of maduramicin (MAD) on breast cancer. However, its poor aqueous solubility and toxicity to normal tissues limit its clinical application. Therefore, to address the drawbacks of MAD and enhance its anticancer and antimetastatic effects, MAD-loaded TPGS polymeric micelles (MAD-TPGS) were prepared by a thin-film hydration technique. The optimized MAD-TPGS exhibited excellent size distribution, stability and improved water solubility. Cellular uptake assays showed that TPGS polymer micelles could enhance drug internalization. Moreover, TPGS synergistically improved the cytotoxicity of MAD by targeting mitochondrial organelles, improving reactive oxygen species levels and reducing the mitochondrial transmembrane potential. More importantly, MAD-TPGS significantly impeded the metastasis of tumor cells. In vivo results further confirmed that, in addition to exhibiting excellent biocompatibility, MAD-TPGS exhibited greater antitumor efficacy than free MAD. Interestingly, MAD-TPGS displayed superior suppression of CMT metastasis via tail vein injection compared to oral administration, indicating its suitability for intravenous delivery. Overall, MAD-TPGS could be applied as a potential antimetastatic cancer agent for CMT.

Esculetin unveiled: Decoding its anti-tumor potential through molecular mechanisms-A comprehensive review.

The growing complexity of cancer has made it a significant concern in the medical community. Although cancer research has advanced, it is still challenging to create new effective medications due to the limitations and side effects of existing treatment strategies. These are enforcing the development of some alternative drugs from natural compounds with fewer drawbacks and side effects. Therefore, this review aims to provide up-to-date, crucial, and all-encompassing data on esculetin's anticancer activity, including all relevant molecular and cellular processes based on in vivo and in vitro investigations. According to the literature review, esculetin is available in nature and is effective against 16 different types of cancer. The general mechanism shown by esculetin is modulating signaling cascades and its related pathways, like cell proliferation, cell growth, autophagy, apoptosis, necrosis, inflammation, angiogenesis, metastasis, invasion, and DNA damage. Nanoformulation of esculetin improves this natural product's efficacy by improving water solubility. Esculetin's synergistic effects with both natural substances and conventional treatments have been shown, and this method aids in reversing resistance mechanisms by modulating resistance-related proteins. In addition, it has fewer side effects on humans than other phytochemicals and standard drugs with some good pharmacokinetic features. Therefore, until standard chemotherapeutics are available in pharmaceutical markets, esculetin should be used as a therapeutic drug against various cancer types.

Development, optimization and in-vivo pharmacokinetic evaluation of flubiprofen nanocrystal tablets for efficient chronotherapy against rheumatoid arthritis

In an effort to enhance drug solubility for buccal mucosal delivery, various strategies such as nanoemulsions, cyclodextrin inclusions, and solid dispersions have been explored, but these methods often face limitations. An emerging solubilization technology, drug nanocrystals, offers a promising alternative due to their high drug loading capacity and scalability for large-scale production. The current study aimed to create solid nanocrystals of flurbiprofen (FP-NC) through a wet milling process to significantly improve water solubility, regardless of pH, and consequently enhance bioavailability. FP-NC was further used to formulate tablets and compressed coatings with carboxymethyl xanthan gum (CXG) and sodium alginate (SA). The compression coating process has been optimized using Quality by Design principles. Utilizing the desirability approach, we identified an optimal formulation with 56.05 mg of CXG, 74.96 mg of SA, and a coating material weight of 249.98 mg. This formulation achieves desired chronotherapeutic characteristics with a lag time (LT) of 5.99 h and T90% of 11.48 h. We conducted in-vitro and ex-vivo drug release studies and compared them with in-vivo pharmacokinetic parameters, employing level A in-vitro in-vivo correlation (IVIVC). Notably, the continuous ex-vivo method exhibited a stronger correlation compared to traditional in-vitro drug release assessments. This suggests that our novel drug release system using the NC compressed coating technique holds promise for achieving chronotherapeutic effects with improved bioavailability.

Discovery of a Highly Potent and Selective MYOF Inhibitor with Improved Water Solubility for the Treatment of Gastric Cancer.

Myoferlin (MYOF) mediates the growth and metastasis of various cancers as an emerging therapeutic target by regulating exocytosis and endocytosis. However, the previously reported MYOF inhibitor, 6y, failed to be a favorable candidate agent due to its poor physicochemical properties, such as water solubility, in preclinical studies. Naturally, a novel range of MYOF inhibitors was synthesized and optimized based on the lead compound 6y. The optimal compound HJ445A potently repressed the proliferation of gastric cancer cells with IC50 values of 0.16 and 0.14 μM in MGC803 and MKN45, respectively. Moreover, HJ445A bound to the MYOF-C2D domain with a KD of 0.17 μM, and HJ445A prevented the migration of gastric cancer cells by reversing the epithelial-mesenchymal transition (EMT) process and inhibited the colony formation of the MKN45 cells in a concentration-dependent manner. Notably, the water solubility of HJ445A was significantly improved compared to 6y, with about 170-fold enhancement. Additionally, HJ445A also demonstrated superior antitumor efficacy in vivo.

Self-assembled low molecular weight chitosan-based cationic micelle for improved water solubility, stability and sustained release of α-tocopherol.

New amphiphilic low molecular weight chitosan-graft-nicotinic acid bearing decyl groups (LCND) was synthesized by two-step reaction and spontaneously assembled into cationic micelle by ultra-sonication method to improve water solubility and photostability properties of α-tocopherol. The chemical structure of LCND was characterized and physical properties of cationic micelle were evaluated. Results displayed that cationic micelle exhibited strong self-assemble ability with nanoscale spherical morphology and showed best loading ability with loading content of 18.50% when the feeding ratio of LCND to α-tocopherol reached 10:3. Meanwhile, the greatly enhanced water solubility, photostability and sustained release behavior of α-tocopherol in cationic micelle were observed. The cumulative release of α-tocopherol in cationic micelle reached up 82.18% within 96h while free α-tocopherol was completely released within 10h. Additionally, release kinetics models were also fitted. The LCND cationic micelle could be promising nanocarrier for improving the physicochemical properties of α-tocopherol in food fields.

How can Fullerenes Help in the Treatment of Diseases? A Review Article on Pharmaceutical Usage of Fullerenes as Carriers.

Drug degradation is a process that can render pharmaceuticals inactive without causing any visible distortion. This can disrupt the therapeutic process, and on occasion, when the process produces toxic metabolites, it can have much more fatal consequences. Light is one of the most significant components that might cause deterioration, and several attempts have been made to improve and increase the practical photosensitizing of nano-scaled pharmaceuticals. Considering this, the insolubility and aggregating qualities of fullerenes have received significant attention. Fullerene is considered to have a unique carbon structure. In order to gain improved water solubility and biocompatible properties, fullerenes have been combined with water-soluble, biodegradable, and adjustable polymers. More specifically, these linkers exhibit increased tumor cell identification and greater tumor cell suppression when linked to therapeutic ligands (tumor-targeting) or stimuliresponsive polymers. According to scientific studies, fullerene-drug combinations can be used in certain complex diseases, like infectious and viral types. Several studies have combined fullerenes into nano-emulsions or liposomes for various pharmacological objectives. In the current work, fullerene/polymer nanomaterials are discussed for potential therapeutic techniques for the treatment of various diseases, particularly cancer and AIDS. According to the research studies, fullerene is a suitable element with outstanding physical and chemical properties that has a wide range of potential applications in the pharmaceutical industry, including drug delivery system design, photodynamic cancer therapy, and antioxidant therapy.

Liver-Targeting Composite Nanocarrier Delivery System Based on Chitosan Nanoparticles and Phospholipid Complexes.

Liver fibrosis is mainly caused by excessive accumulation of extracellular matrix and structural changes in the liver, ultimately leading to cirrhosis if left untreated. Reducing hyaluronan synthesis by inhibiting hyaluronic acid deposition or regulating the expression of hyaluronic synthase can ameliorate liver fibrosis symptoms. In this study, we aimed to improve the bioavailability and liver-targeting capacity of hydroxymethyl coumarin (4-MU) using a newly developed phospholipid complex chitosan nanoparticle (4-MU PC/CNP) optimized using the Box-Behnken design. The composite nanocarrier delivery system was formulated using solvent evaporation technology, and formulation and process parameters were evaluated. Furthermore, 4-MU PC/CNPs and their pharmacokinetics were characterized. The established 4-MU PC/CNPs had an average particle size of 153.07 ± 0.29 nm, a polydispersity index value of 0.383, and a positive zeta potential of ∼35.4 mV. Compared with 4-MUs, 4-MU PC/CNPs exhibited significantly improved water solubility, faster plasma clearance and tissue distribution, and better liver targeting. Pharmacokinetic analysis showed that the oral bioavailability of 4-MU in 4-MU PC/CNPs was significantly higher than that of simple 4-MU. In conclusion, 4-MU PC improved drug lipid (oil-water distribution coefficient of 1.31 ± 0.03) and water solubilities (2.05 times the drug substance). 4-MU PC/CNPs significantly improved 4-MU oral bioavailability, representing a promising approach for enhancing drug solubility. This study demonstrates that the targeting parameters of 4-MU PC/CNPs in the liver were all greater than 1, indicating that they specifically targeted the liver, thereby potentially alleviating liver fibrosis.

Screening of solubilization potential of various green excipients for case of hydrophobic antituberculous thioacetazone

The present study is aimed at solving the problem of poor solubility of the antituberculosis drug thioacetazone (TAZ), the use of which, despite its effectiveness, is limited by toxicity and requires a reduction of the therapeutic dose. Such representatives of "green chemistry" as a deep eutectic solvent based on choline chloride with urea, native and modified cyclodextrins (β-CD and HP-β-CD) and biocompatible polymers (PVP and PEG) were used as solubilizing agents. DES and modified HP-β-CD proved to be the most effective, improving water solubility of TAZ by 106 and 24 times, respectively. β-CD and polymers showed a weak solubilizing potential, demonstrating the ineffectiveness of their application to reduce the hydrophobicity of the drug. In addition, the effect of temperature and concentration of excipients in an aqueous medium on drug dissolution was studied. The thermodynamic aspects of the dissolution and complex formation processes of in the selected systems are also characterized.

Cocrystals of carbamazepine: Structure, mechanical properties, fluorescence properties, solubility, and dissolution rate

Carbamazepine (CBZ) is an anticonvulsant with very low water solubility, presenting as a white crystalline powder with poor mechanical properties and is hard to bend. To enhance CBZ’s physicochemical properties, such as water solubility and mechanical properties, we selected six cocrystal coformers (CCFs): nicotinamide (NIC), benzamide (BZM), salicylic acid (SCA), fumaric acid (FMA), trimesic acid (TMA), and hesperetin (HPE). Six CBZ cocrystals were successfully prepared using the solution method. Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and single crystal X-ray diffraction (SCXRD) were used to characterize the crystal structures and gain comprehensive insights into the six cocrystals. The mechanical, fluorescence, and solubility properties of the six cocrystals were tested. The results reveal that most of the prepared cocrystals exhibit improved water solubility and mechanical properties when compared to CBZ. Among them, the dissolution rate of cocrystals excluded from CBZ-HPE has increased by an average of 3 or 4 times compared to CBZ, while CBZ-HPE exhibits superior mechanical properties. Moreover, all six cocrystals possess better fluorescence performance than CBZ. We thoroughly evaluated the mechanical properties of the cocrystals through both experimental and theoretical approaches. This work provides a new direction for studying drug cocrystals to improve the physicochemical properties of drugs.

Physico-chemical properties of curcumin nanoparticles and its efficacy against Ehrlich ascites carcinoma

Curcumin is a bioactive component with anticancer characteristics; nevertheless, it has poor solubility and fast metabolism, resulting in low bioavailability and so restricting its application. Curcumin loaded in nano emulsions (Cur-NE) was developed to improve water solubility and eliminate all the limitations of curcumin. Size distribution, zeta potential, transmission electron microscopy (TEM) measurements, UV–Visible spectra, IR spectra and thermogravimetric analysis (TGA), were used to characterize the prepared Cur-NE. Cancer therapeutic efficacy was assessed by oxidative stress (superoxide dismutase (SOD), Glutathione–S–Transferase (GST), malondialdehyde (MDA) and nitric oxide (NO), DNA damage, apoptotic proteins (caspase-3 and 9), besides investigating tumor histology and monitoring tumor growth. Additionally, the cytotoxicity and genotoxicity of the liver, kidney, heart, and spleen tissues were examined to gauge the adverse effects of the treatment method’s toxicity. The results showed that Cur-NE is more effective than free curcumin at slowing the growth of Ehrlich tumors while significantly increasing the levels of apoptotic proteins. On the other hand, Cur-NE-treated mice showed some damage in other organs when compared to mice treated with free curcumin. Cur-NE has a higher efficacy in treating Ehrlich tumor.

HH-A, a modified honokiol, protects against cerebral ischemia/reperfusion induced brain injury in rodent via Nrf2/HO-1 signaling pathways.

Honokiol, a bioactive component found in Magnolia officinalis, has shown in protecting against ischemic stroke in animal models. However, its poor water solubility has limited its clinical applications. In this study, we introduced a hydrophilic building block on the aromatic ring of honokiol, resulting in the synthesis of four new compounds (HH-A, -B, -C and -D) with significantly improved water solubility. We then investigated the neuroprotective effects of these compounds in mouse and rat models of transient middle cerebral artery occlusion/reperfusion (tMCAO/R) brain injury. Among the compounds tested, HH-A, also known as (S)-6-((3',5-diallyl-2,4'-dihydroxy-[1,1'-biphenyl]-3-yl)amino)-6-oxohexane-1,5-diaminium chloride, showed the most promising results. HH-A was found to significantly reduced the infarct volume and brain edema in mice. It also outperformed the other three compounds and honokiol, even surpassing the effects of edaravone dexborneol. Additionally, HH-A demonstrated dose-dependent improvements in body weight, neurological deficits, and infarct volume. Further analysis in tMCAO/R rat model revealed that HH-A treatment led to significant upregulations of Nrf2 and HO-1 in the brain. HH-A also significantly reduced the expression of HNE, and exhibited anti-apoptotic effects by decreasing the expression of Bax and increasing the expression of Bcl-2. This was further supported by a decrease in the number of TUNEL positive cells. Taken together, the neuroprotective effects of HH-A may be attributed to its ability to target the Nrf2/HO-1 signaling pathway, leading to reduced oxidative stress and apoptosis in the brain. These findings suggest that HH-A has potential as a therapeutic agent for the treatment of ischemic stroke.

The formulation and invitro evaluation of WS Biotin, a novel encapsulated form of D-Biotin with improved water solubility for hair and skin treatment applications.

To develop and evaluate the efficacy of WS Biotin, a novel water-soluble form of D-Biotin, for cosmetic use. A new encapsulated form of D-Biotin was developed with the purpose of improving the water solubility of biotin. This novel form of encapsulated biotin was characterized by its physicochemical properties: particle size, D-Biotin content and solubility in water. Also, proliferation and gene expression invitro tests in cell culture were performed to evaluate its effectiveness in promoting hair growth, an ELISA test was conducted for hair keratinization and skin lightening property was tested by analysing the intracellular melanin content. The developed WS Biotin microcapsules exhibit a particle size range of 2-30 μm with D-Biotin content of ~50% (w/w). The water solubility of WS Biotin was found to be 20-fold greater than free biotin. The obtained invitro results indicated that WS Biotin enhances the expression of hair-related keratins in hair follicle keratinocytes, as well as the expression of hair growth-promoting genes in dermal papilla cells. Moreover, the melanin content in UVA-exposed epidermal melanocytes was reduced upon exposure to WS Biotin. In this work, a novel form of encapsulated biotin, WS Biotin, was developed in order to improve the water solubility of free biotin and was found to be effective for cosmetic use in both hair and skin applications.

Sugarcane Light-Colored Lignin: A Renewable Resource for Sustainable Beauty.

Lignin has emerged as a promising eco-friendly multifunctional ingredient for cosmetic applications, due to its ability to protect against ultraviolet radiation and its antioxidant and antimicrobial properties. However, its typical dark color and low water solubility limit its application in cosmetics. This study presents a simple process for obtaining light-colored lignin (LCLig) from sugarcane bagasse (SCB) alkaline black liquor, involving an oxidation treatment with hydrogen peroxide, followed by precipitation with sulfuric acid. The physico-chemical characterization, antioxidant and emulsifying potential of LCLig, and determination of its safety and stability in an oil-in-water emulsion were performed. A high-purity lignin (81.6%) with improved water solubility was obtained, as a result of the balance between the total aromatic phenolic units and the carboxylic acids. In addition, the antioxidant and emulsifying capacities of the obtained LCLig were demonstrated. The color reduction treatment did not compromise the safety of lignin for topical cosmetic applications. The emulsion was stable in terms of organoleptic properties (color, pH, and viscosity) and antioxidant activity over 3 months at 4, 25, and 40 °C.

Assessing the effectiveness of fluorinated and α-methylated 3-boronophenylalanine for improved tumor-specific boron delivery in boron neutron capture therapy

A [10B]boron agent and a nuclear imaging probe for pharmacokinetic estimation form the fundamental pair in successful boron neutron capture therapy (BNCT). However, 4-[10B]borono-l-phenylalanine (BPA), used in clinical BNCT, has undesirable water solubility and tumor selectivity. Therefore, we synthesized fluorinated and α-methylated 3-borono-l-phenylalanine (3BPA) derivatives to realize improved water solubility, tumor targetability, and biodistribution. All 3BPA derivatives exhibited over 10 times higher water solubility than BPA. Treatment with α-methylated 3BPA derivatives resulted in decreased cell uptake via l-type amino acid transporter (LAT) 2 while maintaining LAT1 recognition, thereby significantly improving LAT1/LAT2 selectivity. Biodistribution studies showed that fluorinated α-methyl 3BPA derivatives exhibited reduced boron accumulation in nontarget tissues, including muscle, skin, and plasma. Consequently, these derivatives demonstrated significantly improved tumor-to-normal tissue ratios compared to 3BPA and BPA. Overall, fluorinated α-methyl 3BPA derivatives with the corresponding radiofluorinated compounds hold potential as promising agents for future BNCT/PET theranostics.

Production of highly water-soluble genistein α-diglucoside using an engineered O-α-glycoligase with enhanced transglycosylation activity and altered substrate specificity

Genistein is one of isoflavones, showing various biological functions for human health. MalA-D416A, termed O-α-glycoligase, is an acid/base catalytic residue-deficient mutant of a α-glucosidase from Sulfolobus solfataricus, synthesizing genistein 7-O-α-glucoside using α-glucosyl fluoride as the donor substrate. Through mutagenesis toward MalA-D416A, an O-α-glycoligase variant with two mutations (D416R and Q450S) was identified as a biocatalyst with a 58.8-fold enhanced catalytic efficiency for genistein compared to the parent enzyme. The use of a 2:1 ratio of α-glucosyl fluoride and genistein at pH 9 facilitated the synthesis of genistein 7,4′-O-α-diglucoside by MalA-D416R/Q450S. The α-diglucoside exhibited 2,459-fold improved water solubility compared to genistein itself as well as facile deglycosylation by the intestinal α-glucosidase from rat, suggesting the potential of the α-diglucoside for improved bioavailability in human intestine. Through molecular docking analyses the modulation of the active site conformation by these mutations was expected for proper binding of both genistein and the monoglucoside.

Polyglycerol fatty acid ester contributes to the improvement and maintenance of water solubility of amorphous curcumin by suppressing the intermolecular interaction and the diffusion rate of curcumin

Curcumin (CUR), a polyphenol, is an attractive component of functional foods, owing to various physiological activities. However, CUR is highly hydrophobic, insoluble in water, and difficult to absorb in the body. Here, we report an amorphous CUR formulation containing the dispersant polyglycerol fatty acid ester (PGFE), demonstrating high and stable water solubility. Improved water solubility enhanced the absorbability of CUR in our amorphous formulation along with enhanced triglyceride inhibition, compared to that in a commercial formulation. Nuclear Overhauser effect spectroscopy (NOESY) analysis revealed that PGFE reduced CUR-CUR interaction, resulting in higher dispersion and improved solubility of CUR. Taylor dispersion analysis showed a lower diffusion coefficient of CUR in the highly water-soluble formulation (with PGFE) than that in the low water-soluble formulation (without PGFE), which prevents recontact and recrystallization of CUR, which is trapped by PGFE. Overall, the amorphous CUR with high solubility could be used as a promising functional food.

Hypericin supramolecular assembles: A way to increase the skin availability and photodynamic efficiency in tumor cells

Cyclodextrins (CDs) are molecules approved by the FDA and show promise in increasing the solubility of hydrophobic molecules and making them more available to the skin. These CDs have been used to form complexes with some photosensitizers for Photodynamic Therapy (PDT), such as Hypericin (HY). HY is a lipophilic photosensitizer known for its exceptional fluorescence and singlet oxygen quantum yield generation of over 20 % under 590 nm irradiation. In this study, we found a six-fold increase in the release of HY in vitro after complexation with β-CD. The β-CDHY assembly also demonstrated better skin retention, which is crucial for the topical application of this photosensitizer. Furthermore, the β-CD complexation led to a significant increase in the phototoxicity of HY at three different light doses (3, 6, and 10 J cm−2) due to its improved water solubility and higher in vitro accumulation (approximately two times compared with free HY) in HeLa and Vero cell lines.