Hydrophobic Drugs Research Articles

Polyglycerol‐Functionalized β‐Cyclodextrins as Crosslinkers in Thermoresponsive Nanogels for the Enhanced Dermal Penetration of Hydrophobic Drugs (Small 32/2024)

Polyglycerol‐Functionalized β‐Cyclodextrins as Crosslinkers in Thermoresponsive Nanogels for the Enhanced Dermal Penetration of Hydrophobic Drugs (Small 32/2024)

Enhanced Drug Delivery with Oil-in-Water Nanoemulsions: Stability and Sustained Release of Doxorubicin.

In this study, oil-in-water nanoemulsions are prepared, an isotropic mixture of oil, surfactant, and cosurfactants. The nanoemulsions exhibit stable structures and are capable of efficiently encapsulating hydrophobic drugs such as doxorubicin (Dox). Compared to polymeric micelles, nanoemulsions demonstrate enhanced stability and loading capacity for Dox. Furthermore, nanoemulsions release Dox steadily over 14 days, with 51.6% released within the initial 24h and up to 80% over the subsequent period. These properties suggest that nanoemulsions can mitigate the side effects related to the burst release of Dox, thereby improving therapeutic efficacy and safety. Additionally, nanoemulsion-treated cardiomyocytes show increased viability compared to those treated with free Dox, indicating the potential of nanoemulsions to alleviate Dox-induced cardiotoxicity. Overall, nanoemulsions hold promise as versatile and efficient drug carriers for improving cancer treatment outcomes.

Engineering Thermo/pH-Responsive Lactoferrin Nanostructured Microbeads for Oral Targeting of Colorectal Cancer.

Colorectal cancer is an extremely aggressive form of cancer that often leads to death. Lactoferrin shows potential for targeting and treating colorectal cancer; however, oral delivery faces hurdles hampering clinical applications. We engineered dual-responsive lactoferrin nanostructured microbeads to overcome delivery hurdles and enhance drug targeting. The hydrophobic drug mesalazine (MSZ) was coupled to lactoferrin to form amphiphilic conjugate nanoparticles, dispersed in water. The lipid-soluble polyphenolic drug resveratrol (RSV) was then encapsulated into the hydrophobic core of LF-MSZ nanoparticles. To impart thermoresponsive properties, the dual-payload NPs were coupled with a PNIPAAm shell; finally, to further endow the nanoparticles with gastrointestinal resistance and pH responsiveness, the nanoparticles were microencapsulated into ionically cross-linked pectin-alginate beads. The nanoparticles showed enhanced internalization and cytotoxicity against HCT colon cancer cells via LF-receptor-mediated endocytosis. Thermal triggering and tuned release were conferred by the temperature-sensitive polymer. The coatings protected the drugs from degradation. Orally delivered microbeads significantly reduced tumor burden in a mouse colon cancer model, lowering carcinoembryonic antigen and elevating antioxidant enzymes. Apoptotic pathways were stimulated, indicated by heightened Bax/Bcl2 ratio and caspase-3/9 expression. Overall, we propose the innovative lactoferrin nanostructured microbeads as a paradigm shift in oral colorectal cancer therapeutics.

Utilizing Food Waste in 3D-Printed PLA Formulations to Achieve Sustainable and Customizable Controlled Delivery Systems.

This is the first study that explores blending polylactic acid (PLA) with various biomasses, including food wastes-brewer's spent grain (BSG), spent coffee grounds (SCG), sesame cake (SC), and thermoplastic starch (TPS) biomass to create composite gastric floating drug delivery systems (GFDDS) through 3D printing. The aim is to investigate the influence of biomass percentage, biomass type, and printing parameters on their corresponding drug release profiles. 3D-printed (3DP) composite filaments were prepared by blending biomasses and PLA before in vitro drug release studies were performed using hydrophilic and hydrophobic model drugs, metoprolol tartrate (MT), and risperidone (RIS). The data revealed that release profiles were influenced by composite compositions and wall thicknesses of 3DP GFDDS capsules. Up to 15% of food waste could be blended with PLA for all food waste types tested. Delivery studies for PLA-food wastes found that MT was fully released by 4 h, exhibiting burst release profiles after a lag time of 0.5 to 1.5 h, and RIS could achieve a sustained release profile of approximately 48 h. PLA-TPS was utilized as a comparison and demonstrated variable release profiles ranging from 8 to 120 h, depending on the TPS content. The results demonstrated the potential for adjusting drug release profiles by incorporating affordable biomasses into GFDDS. This study presents a promising direction for creating delivery systems that are sustainable, customizable, and cost-effective, utilizing sustainable materials that can also be employed for agricultural, nutraceutical, personal care, and wastewater treatment applications.

Enzyme-Triggered Degradation of Supramolecularly Cross-Linked Polymersomes of Azobenzene-Based Polyurethane: Cell-Selective Anticancer Drug Release.

Enzyme-responsive self-assembled nanostructures for drug delivery applications have gained a lot of attention, as enzymes exhibit dysregulation in many disease-associated microenvironments. Azoreductase enzyme levels are strongly elevated in many tumor tissues; hence, here, we exploited the altered enzyme activity of the azoreductase enzyme and designed a main-chain azobenzene-based amphiphilic polyurethane, which self-assembles into a vesicular nanostructure and is programmed to disassemble in response to a specific enzyme, azoreductase, with the help of the nicotinamide adenine dinucleotide phosphate (NADPH) coenzyme in the hypoxic environment of solid tumors. The vesicular nanostructure sequesters, stabilizes the hydrophobic anticancer drug, and releases the drug in a controlled fashion in response to enzyme-triggered degradation of azo-bonds and disruption of vesicular assembly. The biological evaluation revealed tumor extracellular matrix pH-induced surface charge modulation, selective activated cellular uptake to azoreductase overexpressed lung cancer cells (A549), and the release of the anticancer drug followed by cell death. In contrast, the benign nature of the drug-loaded vesicular nanostructure toward normal cells (H9c2) suggested excellent cell specificity. We envision that the main-chain azobenzene-based polyurethane discussed in this manuscript could be considered as a possible selective chemotherapeutic cargo against the azoreductase overexpressed cancer cells while shielding the normal cells from off-target toxicity.

Self‐Nanoformulating Poly(2‐oxazoline) and Poly(2‐oxazine) Copolymers Based Amorphous Solid Dispersions as Microneedle Patch: A Formulation Study

AbstractA pioneering approach in the domain of transdermal drug delivery systems (TDDS) is introduced by using microneedles (MNs) fabricated from an amorphous solid dispersion comprising only a model drug and an amphiphilic block copolymer to form a drug nanoformulation upon MN dissolution. To maximize drug loading and ensure consistent release, a minimalist formulation that achieves 40 wt% drug loading, which is a significant improvement over existing methods, is developed. Using scanning electron microscopy, the morphology of MNs is examined across a spectrum of drug loading ratios, demonstrating the consistency in structure and integrity. Mechanical testing confirms the MNs' proficiency in effective skin penetration. A comparative study on the formation of polymeric micelles underscores the innovative concept of a “nano‐in‐micro drug delivery system”. The results demonstrate that MNs manufactured from an amorphous solid dispersion of drug and amphiphilic block copolymer with ultra‐high loading enhance the availability and release dynamics of hydrophobic drugs, positioning them as a tool for enhancing TDDS. This study sets a new benchmark in the utilization of polymer‐drug nanoformulations for transdermal applications and underscores the capacity for high drug loading and the creation of adaptable drug delivery mechanisms for the studied amphiphilic block copolymer.

Concentration‐driven morphology change of a self‐aggregated amino acid‐inspired fluorescence‐active copolymer for sustained release of hydrophobic drug

AbstractThe development of amphiphiles for sustained drug delivery represents a promising approach in biomedical fields. Polymeric self‐assembly with a hydrophobic core offers plenty of opportunities to encapsulate hydrophobic drugs for facilitating targeted delivery to the specific sites of action. Herein, N‐Boc tryptophan has been used to develop a hydrophobic monomer, Boc‐tryptophan‐HEMA (HBT). The HBT monomer has further been grafted on modified alginic acid through the RAFT technique to synthesize a unique amphiphilic copolymer with fluorescence characteristics. The advanced polymer chromatography demonstrates a narrow distribution curve, signifying the living nature of polymerization. The copolymer has exhibited self‐aggregation behavior with two distinct shapes at two different critical aggregation concentrations (CAC). The concentration‐dependent shape variation has been investigated using FESEM and TEM analyses, further supported by a small‐angle x‐ray scattering analysis. The self‐aggregation behavior of the copolymer facilitates the uptake of a model hydrophobic drug (naproxen) and its release in a sustained manner with varied rates at two different concentrations.

Ciprofloxacin and Azithromycin Antibiotics Interactions with Bilayer Ionic Surfactants: A Molecular Dynamics Study.

The introduction of pharmaceuticals into aquatic ecosystems can lead to the generation of antibiotic-resistant bacteria. This paper employed molecular dynamics simulations to examine the interactions between cationic/anionic surfactants and two antibiotics or drugs, namely, ciprofloxacin and azithromycin. The analysis focused on many factors to elucidate the mechanism by which the surfactant bilayer molecular structure affects the selected antibiotics. These factors include the tilt angle, rotational angle of the surfactants, electrostatic potential, and charge density along the bilayers. Our molecular-level investigation of the adsorption mechanisms of hydrophobic (azithromycin) and hydrophilic (ciprofloxacin) drugs on the cationic/anionic surfactant bilayer offers a crucial understanding for comprehending the optimal selection of surfactants for effectively separating antibiotics.

Feasibility of Nanostructured Lipid Carrier Loaded with Alpha-Mangostin and Clove Oil for Canine Periodontal Therapy.

Nanostructured lipid carriers (NLC) represent the second generation of nanoparticles, offering numerous advantages over conventional delivery systems. These include improved stability, enhanced drug-loading capacity, and controlled release profiles, making them highly attractive candidates for a wide range of therapeutic applications. Their suitability for hydrophobic drugs like a traditional medicinal plant of Thailand as clove oil and alpha-mangostin. We investigated into nanostructured lipid carriers loaded with Alpha-Mangostin and clove oil (NLC-AMCO) into the physicochemical and biological characteristics to identify the formulation with the highest efficacy for treatment. The particle size, charge, polydispersity index, and other characterizations were recorded. The realtime ex vivo penetration was explored using canine gingival tissue. Drug sustained release was assessed by HPLC. Moreover, the antibacterial properties were tested by conventional methods. The NLC-AMCO can be stored at up to 40 °C for 60 days without any alterations in particle characteristics. Gingival tissue penetration and sustained drug release were superior compared to unencapsulated counterparts. It exhibited greater effectiveness in inhibiting bacterial growth than the antibiotics tested, particularly against bacteria from the oral cavities of dogs. Therefore, this alternative treatment approach offers cost-effectiveness and ease of administration for pet owners and reduces discomfort for the animals during restraint.

Micelle-Containing Hydrogels and Their Applications in Biomedical Research.

Hydrogels are one of the most commonly used materials in our daily lives, which possess crosslinked three-dimensional network structures and are capable of absorbing large amounts of fluid. Due to their outstanding properties, such as flexibility, tunability, and biocompatibility, hydrogels have been widely employed in biomedical research and clinics, especially in on-demand drug release. However, traditional hydrogels face various limitations, e.g., the delivery of hydrophobic drugs due to their highly hydrophilic interior environment. Therefore, micelle-containing hydrogels have been designed and developed, which possess both hydrophilic and hydrophobic microenvironments and enable the storage of diverse cargos. Based on the functionalities of micelles, these hydrogels can be classified into micelle-doped and chemically/physically crosslinked types, which were reported to be responsive to varied stimuli, including temperature, pH, irradiation, electrical signal, magnetic field, etc. Here, we summarize the research advances of micelle-containing hydrogels and provide perspectives on their applications in the biomedical field based on the recent studies from our own lab and others.

STAT3-specific nanocarrier for shRNA/drug dual delivery and tumor synergistic therapy

Non-small cell lung cancer (NSCLC) is a major disease with high incidence, low survival rate and prone to develop drug resistance to chemotherapy. The mechanism of secondary drug resistance in NSCLC chemotherapy is very complex, and studies have shown that the abnormal activation of STAT3 (Signal Transducer and Activator of Transcription 3) plays an important role in it. In this study, the pGPU6/GFP/Neo STAT3-shRNA recombinant plasmid was constructed with STAT3 as the precise target. By modifying hydrophilic and hydrophobic blocks onto chitosan, a multifunctional vitamin E succinate-chitosan-polyethylene glycol monomethyl ether histidine (VES-CTS-mPEG-His) micelles were synthesized. The micelles could encapsulate hydrophobic drug doxorubicin through self-assembly, and load the recombinant pGPU6/GFP/Neo STAT3-shRNA (pDNA) through positive and negative charges to form dual-loaded nanoparticles DOX/VCPH/pDNA. The co-delivery and synergistic effect of DOX and pDNA could up-regulate the expression of PTEN (Phosphatase and Tensin Homolog), down-regulate the expression of CD31, and induce apoptosis of tumor cells. The results of precision targeted therapy showed that DOX/VCPH/pDNA could significantly down-regulate the expression level of STAT3 protein, further enhancing the efficacy of chemotherapy. Through this study, precision personalized treatment of NSCLC could be effectively achieved, reversing its resistance to chemotherapy drugs, and providing new strategies for the treatment of drug-resistant NSCLC.

Sensitive and accurate monitoring of urinary albumin and point-of-care testing using a fluorescent probe with anti-interference capacity against exogenous drugs

Fluorescent probes have been reported for monitoring urinary albumin (u-ALB) to enable early diagnosis of kidney diseases and facilitate regular point-of-care testing (POCT) for chronic kidney disease (CKD) patients. However, the albumin can bind hydrophobic drugs through host-guest interactions, which may result in decreased accuracy of probes at regular drug sites and hamper POCT of albuminuria since CKD patients often need to take medications routinely. Herein, we reported a novel fluorescent probe (NC-2) by molecular engineering of a reported AIEgen (NC-1). The introduction of a non-conjugated ring moiety to the molecular rotor granted the NC-2 enhanced sensitivity with a limit of detection in urine of 8.7 mg/L, which is below l the threshold of microalbuminuria (30 mg/L). Moreover, the NC-2 was found to preferentially bind to the FA1 site of ALB, conferring it with excellent anti-interference capacities against exogenous drug molecules and metabolites. Simulation experiments using lab-spiked urine samples containing common drugs taken by CKD patients demonstrated that the probe could provide satisfied detecting accuracy (80–90 %). Furthermore, a paper-based device was constructed and achieved on-site detection of u-ALB in qualitative and semi-quantitative manners. Findings in this work were of great significance to the development of fluorescent probes for accurate detection of ALB in complex urine samples and the further achievement of fluorescence-based POCT for CKD.

Synthesis and characterization of phthalimide-based niosomes and its investigation as a nano-drug delivery carrier to enhance the therapeutic efficacy of curcumin

To enhance the bioavailability and solubility issues of hydrophobic drugs, the development of cost-efficient nonionic surfactants has attracted scientific interest. The current study focuses on the development of phthalimide-based nonionic surfactant N, N-DPD, and its investigation as a niosomal drug delivery system for enhancing the therapeutic efficacy of curcumin (CUR). Phthalimide-based nonionic surfactant was prepared via aliphatic nucleophilic substitution reaction and characterized by diverse analytical techniques by EI-MS,1H-NMR, and 13C-NMR spectroscopy. Furthermore, the biocompatibility and non-cytotoxicity were evaluated through an MTT assay against the NIH/3T3 cell line. The outcomes showed that the average size of N, N-DPD, and CUR-N, N-DPD vesicles were (277.4 ± 6.2) and (564.7 ± 28.1) nm, and negative zeta potential values (−28.3 ± 1.28) and (−29.2 ± 1.21) mV of these niosomal vesicles were evidence their higher stability. The developed N, N-DPD, and CUR-N, N-DPD vesicles show nearly spherical morphology as elucidated by AFM and SEM images. The CUR-N, N-DPD niosomes showed high drug encapsulation efficiency of about 64.1 ± 10.6 % and higher drug release of 80 ± 2.45 % at pH 6.8. The designed CUR-N, N-DPD niosomal vesicles depicted enhanced anti-inflammatory efficacy when tested against ROS and NO generation in comparison with CUR alone. Moreover, our developed CUR-N, N-DPD vesicles show a significant apoptotic effect against the MCF-7 breast cancer cell line and compared with CUR. The outcomes of the study showed that our developed CUR-N, N-DPD vesicles are efficient in enhancing the therapeutic efficacy of CUR.

Codelivery of methotrexate and silibinin by niosome nanoparticles for enhanced chemotherapy of CT26 colon cancer cells

Colon cancer (CC) is one of the most prevalent cancers in the world, and chemotherapy is widely applied to combat it. However, chemotherapy drugs have severe side effects and emergence of multi drug resistance (MDR) is common. This bottleneck can be overcome by niosome nanocarriers that minimize drug dose/toxicity meanwhile allow co-loading of incompatible drugs for combination therapy. In this research, silibinin (Sil) as a hydrophobic drug was loaded into the lipophilic part, and methotrexate (MTX) into the hydrophilic part of niosome by the thin film hydration (TFH) method to form Nio@MS NPs for CT26 colon cancer therapy in vitro. Our results indicated synthesis of ideal niosome nanoparticles (NPs) with spherical morphology, size of ∼100 nm, and a zeta potential of −10 mV. The IC50 value for Nio@MS was determined ∼2.6 µg ml−1, which was significantly lower than MTX-Sil (∼6.86 µg ml−1), Sil (18.46 µg ml−1 ), and MTX (9.8 µg ml−1 ). Further, Nio@MS significantly reduced cell adhesion density, promoted apoptosis and increased gene expression level of caspase 3 and BAX while promoted significant downregulation of BCL2. In conclusion, the design and application of niosome to co-administer Sil and MTX can increase the drugs cytotoxicity, reduce their dose and improve anti-cancer potential by combating MDR.

Development of Drug-Loaded PCL@MOF Film Enclosed in a Photo Polymeric Container for Sustained Release.

The programmed fabrication of oral dosage forms is associated with several challenges such as controlled loading and disintegration. To optimize the drug payload, excipient breakdown, and site-specific sustained release of hydrophobic drug (sulfamethoxazole, SM), we propose the development of acrylate polymer tablets enclosed with drug-loaded polycaprolactone (PCL) films. The active pharmaceutical ingredient (API) is physisorbed into the porous iron (Fe)-based metal-organic framework (MOF) and later converted to tangible PCL films, which, upon folding, are incorporated into the acrylate polymer matrices (P1/P2/P3). X-ray powder diffraction (XRPD) analysis and scanning electron microscopy (SEM) micrographs confirmed the stability and homogeneous distribution of MOF within the 50 μm thick film. Adsorption-desorption measurements at ambient temperatures confirmed the decrease in the BET surface area of PCL films by 40%, which was ∼3.01 m/g, and pore volume from 30 to 9 nm. The decrease in adsorption and surface parameters could confirm the gradual accessibility of SM molecules once exposed to a degrading environment. Fourier transform infrared (FTIR) analyses of in vitro dissolution confirmed the presence of the drug in the MOF-PCL film-enclosed tablets and concluded the cumulative SM release at pH ∼ 8.2 which followed the order SM@Fe-MOF < P1/P2/P3 < PCL-SM@Fe-MOF < P1/PCL-SM@Fe-MOF < P3/PCL-SM@Fe-MOF. The results of the study indicate that the P3/PCL-SM@Fe-MOF assembly has potential use as a biomedical drug delivery alternative carrier for effective drug loading and stimuli-responsive flexible release to attain high bioavailability.

Phenylboronic Acid‐Functionalized Hyaluronic Acid as Polysaccharide Carriers for Diol‐Containing Drugs Delivery

Packaging hydrophobic drugs into polysaccharide carriers can improve their aqueous solubility, biocompatibility, tumor‐specific accumulation, and therapeutic effect. In this work, phenylboronic acid (PBA) was anchored onto the chain of biocompatible polysaccharide hyaluronic acid (HA) by an amide condensation reaction, which could be used to fabricate stimuli‐responsive targeted drug delivery systems. A series of pH‐responsive conjugated hyaluronic acid nanoparticles composed of a hydrophobic drug core and hydrophilic hyaluronic acid shell were prepared by the boronate‐crosslink of the PBA with diol‐containing anticancer drugs such as capecitabine (CAPE) and aloin (Al). Satisfactory targeted drug release behavior at acidic pH, lower cytotoxicity, and higher anticancer effect were realized by using this polysaccharide carrier. It is believed that this strategy has great potential for polysaccharide modification and anticancer‐associated applications.

Nanosponges-Road Less Explored Changing Drug Delivery Approach: An Explicative Review.

Nanotechnology exhibits a wide range of applications in the domain of disease therapy, diagnosis, biological detection, and environmental safeguards. The cross-linked polymeric nanosponges (NSs) are a nanoscale drug carrier system with a 3D porous structure and high entrapment efficacy. NSs up to the fourth generation are currently accessible and can serve as a delivery system for both hydrophilic and hydrophobic drugs. The delivery system exhibits superiority over alternative methods due to its ability to achieve controlled and targeted drug delivery. The colloidal structure of NSs facilitates the encapsulation of a wide range of agents such as proteins and peptides, enzymes, antineoplastic drugs, volatile oil, vaccines, DNA, etc. NSs efficiently overcome the challenges associated with drug toxicity and poor aqueous solubility. NS formulations have been explored for various applications like gaseous encapsulation, enzyme immobilization, antifungal therapy, poison absorbent, water purification, etc. This review provides a comprehensive analysis regarding methods of synthesis, distinct polymeric NSs, mechanism of drug release, factors affecting NS development, applications, and patents filed in the field of NSs. Herein, the recently developed NS formulations, their potential in cancer therapy, and current progressions of NS for SARS-CoV-2 management are also deliberated with special attention, focusing on the significant challenges and future directions.

Surface Modification of Mesoporous Silica Nanoparticles as a Means to Introduce Inherent Cancer‐Targeting Ability in a 3D Tumor Microenvironment

Mesoporous silica nanoparticles (MSNs) have emerged as promising drug carriers that can facilitate targeted anticancer drug delivery, but efficiency studies relying on active targeting mechanisms remain elusive. This study implements in vitro 3D cocultures, so‐called microtissues, to model a physiologically relevant tumor microenvironment (TME) to examine the impact of surface‐modified MSNs without targeting ligands on the internalization, cargo delivery, and cargo release in tumor cells and cancer‐associated fibroblasts. Among these, acetylated MSNs most effectively localized in tumor cells in a 3D setting containing collagen, while other MSNs did so to a lesser degree, most likely due to remaining trapped in the extracellular matrix of the TME. Confocal imaging of hydrophobic model drug‐loaded MSNs demonstrated effective cargo release predominantly in tumor cells, both in 2D and 3D cocultures. MSN‐mediated delivery of an anticancer drug in the microtissues exhibited a significant reduction in tumor organoid size and enhanced the tumor‐specific cytotoxic effects of a γ‐secretase inhibitor, compared to the highly hydrophobic drug in free form. This inherent targeting potential suggests reduced off‐target effects and increased drug efficacy, showcasing the promise of surface modification of MSNs as a means of direct cell‐specific targeting and delivery for precise and successful targeted drug delivery.

Core-Tunable Dendritic Polymer: A Folate-Guided Theranostic Nanoplatform for Drug Delivery Applications.

Clinical application of anticancer drugs is mostly limited due to their hydrophobic nature, which often results in lower bioavailability and lesser retention in systemic circulation. Despite extensive research on the development of targeted drug delivery systems for cancer treatment, delivery of hydrophobic therapeutic drugs to tumor cells remains a major challenge in the field. To address these concerns, we have precisely engineered a new hyperbranched polymer for the targeted delivery of hydrophobic drugs by using a malonic acid-based A2B monomer and 1,6-hexanediol. The choice of monomer systems in our design allows for the formation of higher molecular weight polymers with hydrophobic cavities for the efficient encapsulation of therapeutic drugs that exhibit poor water solubility. Using several experimental techniques such as NMR, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform-infrared (FT-IR), and gel permeation chromatography (GPC), the synthesized polymer was characterized, which indicated its dendritic structure, thermal stability, and amorphous nature, making it suitable as a drug delivery system. Following characterizations, theranostic nanoplatforms were formulated using a one-pot solvent diffusion method to coencapsulate hydrophobic drugs, BQU57 and doxorubicin. To achieve targeted delivery of loaded therapeutic drugs in A549 cancer cells, the surface of the polymeric nanoparticle was conjugated with folic acid. The therapeutic efficacy of the delivery system was determined by various cell-based in vitro experiments, including cytotoxicity, cell internalizations, reactive oxygen species (ROS), apoptosis, migration, and comet assays. Overall, findings from this study indicate that the synthesized dendritic polymer is a promising carrier for hydrophobic anticancer drugs with higher biocompatibility, stability, and therapeutic efficacy for applications in cancer therapy.

Modulation of mechanical properties of low molecular weight supramolecular hydrogels of calcium cholate by drugs of varying hydrophobicity: Effect on drug release, antioxidant, and antibacterial properties

Bile salt based low-molecular-weight supramolecular hydrogels (LMWSH) serve as an appealing framework for drug delivery applications, owing to their natural origin, biocompatibility, and the peculiar distribution of hydrophobic and hydrophilic domains. In this work, LMWSH based on an ionotropic gel of sodium cholate assisted by Ca2+ ions (CaC) was developed as a drug delivery system for both hydrophilic and hydrophobic drugs. Diosgenin, Quercetin, Rutin, and Amygdalin were chosen as model drugs, having varying hydrophobicity. The mechanical strength of the CaC hydrogel is enhanced by increasing the hydrophobicity of the loaded drug. The close-knit mesh design of CaC hydrogels loaded with hydrophobic drugs resulted in controlled drug release compared to the hydrophilic drugs. Drug-loaded CaC hydrogels exhibited good swelling and thixotropy, making them suitable for injectable formulations. In kinetic drug release, both relaxation and diffusion mechanisms play a pivotal role. The antioxidant and antibacterial activity of the loaded drugs increased synergistically in the hydrogels. Thus, due to these properties, the hydrogels can be safely used as topical gels against wound healing. This study shows that bile salts exhibit potential to enhance the delivery of both hydrophobic and hydrophilic drugs, making them promising candidates for biomedical applications.