Enhance Drug Solubility Research Articles

Enhancing Drug Solubility, Bioavailability, and Targeted Therapeutic Applications through Magnetic Nanoparticles

Biological variability poses significant challenges in the development of effective therapeutics, particularly when it comes to drug solubility and bioavailability. Poor solubility across varying physiological conditions often leads to reduced absorption and inconsistent therapeutic outcomes. This review examines how nanotechnology, especially through the use of nanomaterials and magnetic nanoparticles, offers innovative solutions to enhance drug solubility and bioavailability. This comprehensive review focuses on recent advancements and approaches in nanotechnology. We highlight both the successes and remaining challenges in this field, emphasizing the role of continued innovation. Future research should prioritize developing universal therapeutic solutions, conducting interdisciplinary research, and leveraging personalized nanomedicine to address biological variability.

Serum Albumin in Nasal Drug Delivery Systems: Exploring the Role and Application

The application of serum albumin in various types of formulations has emerged as a valuable option in biomedical research, especially in the field of nasal drug delivery systems. A serum albumin-based carrier system has been employed due to several benefits, such as enhancing drug solubility and stability, generating the desired controlled release profile, and developing favorable properties with respect to the challenges in nasal conditions, which, in this case, involves hindering rapid elimination due to nasal mucociliary clearance. Accordingly, considering the important role of serum albumin, in-depth knowledge related to its utilization in preparing nasal drug formulation is highly encouraged. This review aimed to explore the potential application of serum albumin in fabricating nasal drug formulations and its crucial role and functionality regarding the binding interaction with nasal mucin, which significantly determines the successful administration of nasal drug formulations.

Lipid-Based Nanoparticles as Drug Delivery System for Modern Therapeutics.

The emergence of lipid-based nanoparticulate systems has significantly reshaped the landscape of drug delivery. This review aims to encapsulate the advancements, challenges, and potential of lipid-based nanoparticulate drug delivery in modern therapeutics. Lipid-based nanoparticles, including liposomes, lipid nanoparticles, and solid lipid nanoparticles, harness the biocompatibility and biodegradability of lipids to encapsulate and deliver a diverse range of therapeutic agents. This platform offers solutions to various drug delivery challenges, such as enhancing drug solubility and bio- availability, achieving controlled and sustained release, targeted delivery, and co-delivery of multi-agents. These nanoparticles have demonstrated potential in overcoming biological barriers, including the blood-brain barrier, mucosal barriers, and cellular barriers, enabling the delivery of drugs to previously inaccessible sites. Biocompatibility and reduced toxicity are intrinsic attributes of lipid-based nanoparticles, minimizing immune responses and systemic toxicity while promoting personalized medicine possibilities. However, challenges in formulation, stability, and regulatory approval underscore the need for ongoing research and innovation in this field.

Recent Advancement of Novel Drug Delivery Systems for Topical Anaesthesia Formulations

Abstract: In recent years, there have been exciting developments in improving how we deliver anaesthesia through the skin. Nanotechnology is a key player, using tiny particles to encapsulate and transport anaesthetic agents, ensuring a controlled and steady release. This helps overcome challenges like inconsistent absorption and short-lasting effects seen with traditional methods. Transdermal patches are gaining attention too; they release drugs slowly and steadily, eliminating the need for frequent reapplication while maintaining a constant drug level at the application site. Smart polymers are bringing innovation by responding to specific triggers, enabling on-demand drug release. This allows for personalized anaesthesia based on individual patient needs. In recent years, there have been exciting developments in improving how we deliver anaesthesia through the skin. Nanotechnology is a key player, using tiny particles to encapsulate and transport anaesthesia agents, ensuring a controlled and steady release. This helps overcome challenges like inconsistent absorption and other short-lasting effects seen with traditional methods. Microemulsion systems, made of water, oil, surfactants, and co-surfactants, are another promising approach. They enhance drug solubility and availability, providing a stable environment for including anaesthesia agents. Transdermal patches are gaining attention too; they release drugs slowly and steadily, eliminating the need for frequent reapplication and maintaining a constant drug level at the application site. Smart polymers are bringing innovation by responding to specific triggers, enabling on-demand drug release. This allows for personalized anaesthesia based on individual patient needs. Together, these advancements mark a significant shift towards more effective, patient-friendly, and personalized topical anaesthesia delivery systems.

Nanoemulgel: A Comprehensive Review of Formulation Strategies, Characterization, Patents and Applications

<p>Background: Delivering hydrophobic or poorly soluble drugs has become increasingly challenging, with issues like stability and bioavailability complicating the process. Among various strategies devised to address these problems, nanoemulgels have proven effective. Nanoemulgels combine a gel base and an emulsion at the nanoscale, making them excellent for drug delivery. The nanoemulsion component protects the active ingredient from degradative reactions like hydrolysis and enzymatic degradation. Meanwhile, the gel base enhances the emulsion's thermodynamic stability by increasing the viscosity of the aqueous phase and reducing surface and interfacial tension. </p><p> Objective: The primary objective of this review was to explore nanoemulgels as a drug delivery system in the pharmaceutical industry. It delves into the advantages and applications of nanoemulgels in various medical fields, compares them with conventional emulgel, and examines formulation strategies, preparation methods, patent trends, future prospects, and evaluation methods in detail. </p><p> Method: An exhaustive literature survey was conducted keeping in view the various aspects of nanoemulgel. Information from various resources, such as books, review articles, scientific reports, research articles, and patents, were searched, read, analyzed, and summarized. </p><p> Conclusion: This review article thoroughly examines nanoemulgels, discussing their formulation strategies, characterization techniques, and applications in various fields. It highlights their benefits, such as enhanced drug solubility, controlled release, improved stability, and targeted delivery. The article also covers patents related to nanoemulgel technology and explores its future prospects, emphasizing potential applications in pharmaceuticals, cosmetics, dermatology, and other industries.</p>

Lipid-based nanoparticles: innovations in ocular drug delivery.

Ocular drug delivery presents significant challenges due to intricate anatomy and the various barriers (corneal, tear, conjunctival, blood-aqueous, blood-retinal, and degradative enzymes) within the eye. Lipid-based nanoparticles (LNPs) have emerged as promising carriers for ocular drug delivery due to their ability to enhance drug solubility, improve bioavailability, and provide sustained release. LNPs, particularly solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and cationic nanostructured lipid carriers (CNLCs), have emerged as promising solutions for enhancing ocular drug delivery. This review provides a comprehensive summary of lipid nanoparticle-based drug delivery systems, emphasizing their biocompatibility and efficiency in ocular applications. We evaluated research and review articles sourced from databases such as Google Scholar, TandFonline, SpringerLink, and ScienceDirect, focusing on studies published between 2013 and 2023. The review discusses the materials and methodologies employed in the preparation of SLNs, NLCs, and CNLCs, focusing on their application as proficient carriers for ocular drug delivery. CNLCs, in particular, demonstrate superior effectiveness attributed due to their electrostatic bioadhesion to ocular tissues, enhancing drug delivery. However, continued research efforts are essential to further optimize CNLC formulations and validate their clinical utility, ensuring advancements in ocular drug delivery technology for improved patient outcomes.

Deep Eutectic Solvents Enhancing Drug Solubility and Its Delivery.

Deep eutectic solvents (DES) are environmentally friendly solvents with the potential to dissolve bioactive compounds without affecting their characteristics. DES has special qualities that can be customized to meet the unique characteristics of a biomolecule/active pharmaceutical ingredient (API) in accordance with various therapeutic needs, providing a reliable approach in opening the door for the creation of cutting-edge drug formulations by resolving solubility issues in pharmaceutics. This study outlines newly developing approaches to solve the problem of inefficient API extraction due to poor solubility. These emerging strategies also have the capacity to alter the chemical and physical stability of API, which triggers drug's shelf life and their possible health benefits. It is anticipated that the highlighted methods and processes will be developed to capitalize on the DES potential to improve drug solubility and delivery in the pharmaceutical sector.

Mechanism of Self-Assembled Celastrol-Erianin Nanomedicine for treatment of breast cancer

Apoptosis as a common form of programmed cell death, plays a crucial role in tumor therapy. Celastrol and erianin are natural compounds extracted from plants. Celastrol exhibits cytotoxic effects on various tumor cells through mechanisms such as ferroptosis and apoptosis, while erianin significantly inhibits the growth and metastasis of cancer cells. However, the high toxicity of celastrol and the low water solubility of both compounds hinder their clinical applications. In this study, nanoparticles (CEN) self-assembled from celastrol and erianin were designed to enhance drug solubility and tumor-targeting capability. These nanoparticles significantly inhibited the proliferation of tumor cells while effectively killing the entire tumor cell population. Additionally, using activity-based protein profiling (ABPP) and a celastrol-probe (cel-p), Annexin A2 was identified as the target of celastrol in 4 T1 cells. Proteomics was subsequently used to evaluate the changes in protein expression induced by CEN. In a mouse model of breast cancer, CEN demonstrated superior tumor-targeting ability and prolonged action due to the enhanced permeability and retention (EPR) effect, resulting in better therapeutic efficacy with lower systemic toxicity. In conclusion, this study provides a novel reference for the treatment of breast cancer.

A SYSTEMATIC REVIEW OF THE EFFECTIVENESS OF TURMERIC IN THE TREATMENT OF BREAST CANCER

Breast cancer remains a significant global health concern, necessitating the exploration of innovative therapeutic strategies. Curcumin, a bioactive compound derived from turmeric, has garnered considerable attention due to its diverse pharmacological properties, including anticancer effects. However, the clinical translation of curcumin is hampered by its poor bioavailability. Nanoformulations of curcumin, particularly Cur-NPs, offer a promising solution to this challenge by enhancing drug solubility, stability, and targeted delivery. This in-depth abstract delves into the potential of Cur-NPs as a therapeutic approach for breast cancer treatment. The systematic review included in vivo studies investigating the efficacy and toxicity of Cur-NPs in breast cancer models. Notably, Cur-NPs demonstrated significant antitumoral activity across diverse breast cancer models, attributed to mechanisms such as apoptosis induction, inhibition of proliferation, and suppression of angiogenesis. Moreover, Cur-NPs exhibited minimal toxicity, with no or low adverse effects observed in terms of body weight, organ histopathology, and hematological/biochemical parameters. Characterization of Cur-NPs revealed a diverse array of nanoparticle types, including polymer NPs, micelles, lipid-based NPs, and metal NPs. Poly(ethylene glycol) chains were commonly incorporated into NP compositions, enhancing their biocompatibility and circulation time. Targeting moieties such as folic acid and hyaluronic acid further augmented the specificity of drug delivery to breast cancer cells. Experimental design varied among studies, encompassing different animal models, routes of administration, and treatment durations. Intravenous administration emerged as the predominant route, although alternative routes such as intraperitoneal and intratumoral administration were also explored. The onset of treatment protocols varied based on days after tumour induction or tumour volume, with curcumin doses ranging from 2 to 100 mg/kg and administered with varying frequencies. In conclusion, Cur-NPs represent a promising therapeutic approach for breast cancer treatment, offering enhanced efficacy and safety profiles compared to free curcumin. Further research is warranted to optimize Cur-NP formulations and elucidate their clinical potential in breast cancer patients. The review also identified a diverse array of nanoparticle formulations employed in breast cancer therapy, including liposomes, polymeric nanoparticles, micelles, and dendrimers. These nanoparticles were engineered to encapsulate various anticancer drugs, including chemotherapeutic agents, molecularly targeted therapies, and immunomodulators, with the aim of enhancing their efficacy and reducing systemic toxicity. Targeted drug delivery strategies were employed to selectively deliver therapeutic agents to tumour cells while sparing healthy tissues, thereby minimizing off-target effects and improving treatment outcomes. Preclinical studies provided compelling evidence of the efficacy of nanoparticle-based therapies in inhibiting tumour growth, suppressing metastasis, and overcoming drug resistance in breast cancer models. Nanoparticles demonstrated superior pharmacokinetic properties, enhanced bioavailability, and controlled drug release kinetics, leading to improved therapeutic efficacy compared to conventional formulations. Furthermore, nanoparticle-based therapies exhibited synergistic effects when combined with traditional chemotherapy agents, leading to enhanced antitumor activity and reduced treatment resistance. Clinical studies evaluating the safety and efficacy of nanoparticle-based therapies in breast cancer patients demonstrated promising results, with favourable tolerability profiles and encouraging preliminary efficacy outcomes. However, challenges remain in translating preclinical findings into clinical practice, including issues related to scalability, manufacturing, and regulatory approval. Additionally, further research is needed to optimize nanoparticle formulations, tailor treatment strategies to individual patient profiles, and elucidate long-term safety and efficacy outcomes.

A Comprehensive Review on Co-Crystals: Transforming Drug Delivery with Enhanced Solubility and Bioavailability

Poor solubility and bioavailability of various drug compounds are the biggest challenges faced by researchers and industrialists, hindering their therapeutic efficacy. Researchers have developed a versatile approach to enhance the solubility and bioavailability of the drug i.e., co-crystallization. Pharmaceutical co-crystals are solid, crystalline materials consisting of API and co-formers that have supramolecular chemistry with one another. Co-crystallization helps in enhancing a drug’s physico-chemical properties, such as bioavailability, solubility and dissolution, preserving its therapeutic effect. The API and co-former in co-crystals are bound to each other via hydrogen bonding, π-stacking, and Van der Waals forces. Several methods to prepare co-crystals, such as solvent evaporation method, grinding method, cooling crystallization method, etc, and various research reports, including all the methods of preparation are discussed in this review article. Conventional marketed products and patents on co-crystals are also included. Data has been gathered, and relevant literature reports have been examined utilizing a variety of search engines, including Google Scholar, ScienceDirect, Pubmed, and Google patents. After reviewing the literature, the researchers found that the cocrystallization method is one the simplest method to enhance drug bioavailability and solubility. Moreover, it enhances the pharmacokinetics parameters, pharmacodynamics properties, and melting point of the drug. In this review article, the researchers have compiled the recent literature reports on enhanced drug solubility via co-crystallization method. The researchers concluded that this review article can help other researchers by providing them with recent literature on this article and can compare the various methods of enhancing drug solubility and bioavailability. It also consists of compiled data of patents and marketed formulations prepared by the co-crystallization technique. Thus, co-crystallization could be established as a versatile approach for enhancing drug solubility and bioavailability.

Exploring lipids: A comprehensive review on their utilization in the formulation of liposomes, phytosomes, and ethosomes for advanced drug delivery systems"

This comprehensive review explores the diverse applications of lipids in the formulation of advanced drug delivery systems, specifically focusing on liposomes, phytosomes, and ethosomes. Lipids, crucial components in these formulations, play a pivotal role in enhancing drug solubility, stability, and bioavailability. The review systematically examines the latest advancements in lipid-based delivery systems, shedding light on their unique characteristics and applications. In the realm of liposomes, the study delves into various lipid compositions, highlighting their influence on liposomal structure and function. Additionally, the review explores the integration of phytosomes, which involve the complexation of drugs with plant-derived phospholipids, showcasing their potential to improve therapeutic efficacy. Ethosomes, lipid vesicles containing high concentrations of ethanol, are also extensively discussed, emphasizing their ability to enhance transdermal drug delivery. Critical analyses of recent research findings, including the impact of lipid selection on vesicle stability, drug release kinetics, and pharmacokinetics, are presented. The review further examines the challenges associated with lipid-based formulations, providing insights into potential avenues for future research and development. By synthesizing current knowledge, this review serves as a valuable resource for researchers, clinicians, and pharmaceutical scientists seeking a comprehensive understanding of the role of lipids in optimizing liposomal, phytosomal, and ethosomal drug delivery systems.

Development and optimization of a self micro-emulsifying drug delivery system (SMEDDS) for co-administration of sorafenib and curcumin.

In this study, we developed a novel co-administration of curcumin and sorafenib using a Self micro-emulsifying Drug Delivery System (SMEDDS) called Sorafenib-Curcumin Self micro-emulsifying Drug Delivery System (SOR-CUR-SMEDDS). The formulation was optimized using star point design-response surface methodology, and in vitro cellular experiments were conducted to evaluate the delivery ratio and anti-tumor efficacy of the curcumin and sorafenib combination. The SOR-CUR-SMEDDS exhibited a small size distribution of 13.48 ± 0.61nm, low polydispersity index (PDI) of 0.228 ± 0.05, and negative zeta potential (ZP) of - 12.4 mV. The half maximal inhibitory concentration (IC50) of the SOR-CUR-SMEDDS was 3-fold lower for curcumin and 5-fold lower for sorafenib against HepG2 cells (human hepatocellular carcinoma cells). Transmission electron microscopy (TEM) and particle size detection confirmed that the SOR-CUR-SMEDDS droplets were uniformly round and within the nano-emulsion particle size range of 10-20nm. The SMEDDS were characterized then studied for drug release in vitro via dialysis membranes. Curcumin was released more completely in the combined delivery system, showing the largest in vitro drug release (79.20%) within 7 days in the medium, while the cumulative release rate of sorafenib in the release medium was low, reaching 58.96% on the 7day. In vitro pharmacokinetic study, it demonstrated a significant increase in oral bioavailability of sorafenib (1239.88-fold) and curcumin (3.64-fold) when administered in the SMEDDS. These findings suggest that the SMEDDS formulation can greatly enhance drug solubility, improve drug absorption and prolong circulation in vivo, leading to increased oral bioavailability of sorafenib and curcumin.

Exploring physicochemical characteristics of cyclodextrin through M-polynomial indices

Cyclodextrin, a potent anti-tumor medication utilized predominantly in ovarian and breast cancer treatments, encounters significant challenges such as poor solubility, potential side effects, and resistance from tumor cells. Combining cyclodextrin with biocompatible substrates offers a promising strategy to address these obstacles. Understanding the atomic structure and physicochemical properties of cyclodextrin and its derivatives is essential for enhancing drug solubility, modification, targeted delivery, and controlled release. In this study, we investigate the topological indices of cyclodextrin using algebraic polynomials, specifically the degree-based M-polynomial and neighbor degree-based M-polynomial. By computing degree-based and neighbor degree-based topological indices, we aim to elucidate the structural characteristics of cyclodextrin and provide insights into its physicochemical behavior. The computed indices serve as predictive tools for assessing the health benefits and therapeutic efficacy of cyclodextrin-based formulations. In addition, we examined that the computed indices showed a significant relationship with the physicochemical characteristics of antiviral drugs. Graphical representations of the computed results further facilitate the visualization and interpretation of cyclodextrin's molecular structure, aiding researchers in designing novel drug delivery systems with improved pharmacological properties.

An approach to enhance drug solubility: fabrication, characterization, and safety evaluation of Felodipine polymeric nanoparticles

An approach to enhance drug solubility: fabrication, characterization, and safety evaluation of Felodipine polymeric nanoparticles

Metal-organic frameworks in oral drug delivery

Metal-organic frameworks (MOFs) offer innovative solutions to the limitations of traditional oral drug delivery systems through their unique combination of metal ions and organic ligands. This review systematically examines the structural properties and principles of MOFs, setting the stage for their application in drug delivery. It discusses various classes of MOFs, including those based on zirconium, iron, zinc, copper, titanium, aluminum, potassium, and magnesium, assessing their drug-loading capacities, biocompatibility, and controlled release mechanisms. The effectiveness of MOFs is illustrated through case studies that highlight their capabilities in enhancing drug solubility, providing protection against the harsh gastrointestinal environment, and enabling precise drug release. The review addresses potential challenges, particularly the toxicity concerns associated with MOFs, and calls for further research into their biocompatibility and interactions with biological systems. It concludes by emphasizing the potential of MOFs in revolutionizing oral drug delivery, highlighting the critical need for comprehensive research to harness their full potential in clinical applications.

Combination of machine learning and COSMO-RS thermodynamic model in predicting solubility parameters of coformers in production of cocrystals for enhanced drug solubility

In this study, we develop predictive models for three target variables, denoted as δd, δp, and δh using a dataset with 86 features and 181 samples. The response parameters, which are Hansen solubility parameters, were correlated to input parameters via several machine learning techniques. The input features are molecular descriptors of coformers which are calculated based on COMSO-RS thermodynamic model and group contribution approach. The analysis includes outlier detection via Cook's distance, normalization with a min-max scaler, and feature selection through L1-based methods. Three regression models—Gaussian Process Regression (GPR), Passive Aggressive Regression (PAR), and Polynomial Regression (PR)—are employed, with hyperparameter optimization achieved using Transient Search Optimization (TSO). The results indicate that for δd, the PAR model outperforms others with an R2 score of 0.885, RMSE of 0.607, MAE of 0.524, and a maximum error of 1.294. The GPR model shows slightly lower performance with an R2 of 0.872, RMSE of 0.816, MAE of 0.579, and a maximum error of 2.755 for δd. The PR model performs on δd with an R2 of 0.814, RMSE of 0.923, MAE of 0.597, and a maximum error of 2.814. For δp, the GPR model provides the best performance, achieving an R2 score of 0.821, RMSE of 1.693, MAE of 1.391, and a maximum error of 3.457. The PAR model performs on δp with an R2 of 0.740, RMSE of 2.025, MAE of 1.980, and a maximum error of 6.609. Also, The PR model predicts δp with a R2 of 0.7, RMSE of 2.329, MAE of 2.02, and maximum error of 6.366. Similarly, for δh, the GPR model again shows superior performance with an R2 score of 0.983, RMSE of 1.243, MAE of 1.005, and a maximum error of 2.577. The PAR model also accurately predicts δh with a R2 of 0.924, RMSE of 2.713, MAE of 2.416, and maximum error of 6.307. Additionally, the PR model predicts δh with a R2 of 0.927, RMSE of 2.757, MAE of 2.334, and maximum error of 8.064. These results highlight the efficacy of the chosen models and optimization techniques in accurately predicting the specified outputs, demonstrating significant potential for application in relevant predictive modeling tasks.

PEGylation in Pharmaceutical Development: Current Status and Emerging Trends in Macromolecular and Immunotherapeutic Drugs.

The purpose of the research is to examine the advantages and difficulties of target-site drug delivery methods, with an emphasis on the application of polyethylene glycol (PEG) to enhance drug solubility, bioavailability, and immune response characteristics. It has been demonstrated that this method lowers immunogenicity, enhances pharmacokinetics, and helps drugs pass the blood-brain barrier while reducing reticuloendothelial system clearance. PEG and its derivatives are being used more and more to alter therapeutic substances, offering an escape from some of the drawbacks of conventional medication formulations. In the review, different PEGylation tactics are examined, including cutting-edge methods for reversing multi-drug resistance in nanocarriers. PEGylation has a number of benefits, but there are still drawbacks, including the immunogenic reaction to PEG, which is sometimes referred to as "anti-PEG antibodies," and stability problems that call for the creation of countermeasures. The study devotes a large amount of its space to listing FDA-approved PEGylated medications, emphasizing their therapeutic advantages and clinical uses in a range of medical specialties. The research also explores the regulatory environment that surrounds PEG, closely examining its effectiveness and safety in medication compositions. The review goes beyond PEGylation and includes lipid-based nanocarriers, including liposomes, nanostructured lipid carriers (NLCs), and solid lipid nanoparticles (SLNs). Because these nanocarriers can target specific tissues or cells, improve bioavailability, and encapsulate pharmaceuticals, they are becoming more and more significant in drug delivery systems. The Target Product Profile (TPP) and Quality by Design (QbD) principles serve as the foundation for the creation and characterization of these lipid-based systems. These tools direct the methodical assessment of material properties and risk assessments during the formulation phase. This method guarantees that the finished product satisfies the appropriate requirements for efficacy, safety, and quality. The regulatory status and safety profile of nano lipid carriers are covered in the paper's conclusion, which emphasizes the importance of careful examination and oversight in bringing these cutting-edge products to market. Overall, this thorough analysis highlights the revolutionary potential of lipid-based nanocarriers and PEGylation in improving drug delivery and therapeutic efficacy, but it also draws attention to the continued difficulties and legal issues that need to be resolved in order to fully reap the benefits of these technologies in biomedicine.

An insight into pharmaceutical challenges with ionic liquids: where do we stand in transdermal delivery?

Ionic liquids (ILs) represent an exciting and promising solution for advancing drug delivery platforms. Their unique properties, including broad chemical diversity, adaptable structures, and exceptional thermal stability, make them ideal candidates for overcoming challenges in transdermal drug delivery. Despite encountering obstacles such as side reactions, impurity effects, biocompatibility concerns, and stability issues, ILs offer substantial potential in enhancing drug solubility, navigating physiological barriers, and improving particle stability. To propel the use of IL-based drug delivery in pharmaceutical innovation, it is imperative to devise new strategies and solvents that can amplify drug effectiveness, facilitate drug delivery to cells at the molecular level, and ensure compatibility with the human body. This review introduces innovative methods to effectively address the challenges associated with transdermal drug delivery, presenting progressive approaches to significantly improve the efficacy of this drug delivery system.

Development, Characterization, and Cellular Toxicity Evaluation of Solid Dispersion-Loaded Hydrogel Based on Indomethacin.

Indomethacin (IND) as a non-selective cyclooxygenase 1 and 2 inhibitor administered orally causes numerous adverse effects, mostly related to the gastrointestinal tract. Moreover, when applied exogenously in topical preparations, there are obstacles to its permeation through the stratum corneum due to its low water solubility and susceptibility to photodegradation. In this work, solid dispersions (SDs) of IND with low-substituted hydroxypropyl cellulose (LHPC) were developed. The IND-SDs were incorporated into a hydroxypropyl guar (HPG) hydrogel to enhance drug solubility on the skin. The hydrogels were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD), Fourier-transform infrared spectroscopy (FTIR), viscosity, drug release, and unspecific cytotoxicity in mammalian cells. SEM showed a highly porous structure for SD hydrogels. DSC and XRPD studies showed that amorphous IND species were formed; therefore, these hydrogels exhibited superior drug release in comparison with IND raw material hydrogels. FTIR evidenced the presence of the hydrogen bond in the SD hydrogel. The rheology parameter viscosity increased across gels formulated with SDs in comparison with hydrogels with pure IND. In addition, IND-SD hydrogels combine the advantages of a suitable viscosity for dermal use and no potentially hazardous skin irritation. This study suggests that the formulated IND-SD hydrogels represent a suitable candidate for topical administration.

Molecular insights into the interactions between PEG carriers and drug molecules from Celastrus hindsii: a multi-scale simulation study

Efficient drug delivery is crucial for the creation of effective pharmaceutical treatments, and polyethylene glycol (PEG) carriers have been emerged as promising candidates for this purpose due to their bio-compatibility, enhancement of drug solubility, and stability. In this study, we utilized molecular simulations to examine the interactions between PEG carriers and selected drug molecules extracted from Celastrus hindsii: Hindsiilactone A, Hindsiiquinoflavan B, Maytenfolone A, and Celasdin B. The simulations provided detailed insights into the binding affinity, stability, and structural properties of these drug molecules when complexed with PEG carriers. A multi-scale approach combining density functional theory (DFT), extended tight-binding (xTB), and molecular dynamics (MD) simulations was conducted to investigate both unbound and bound states of PEG/drug systems. The results from DFT and xTB calculations revealed that the unbound complex has an unfavorable binding free energy, primarily due to negative contributions of delta solvation free energy and entropy. The MD simulations provided more detailed insights into the interactions between PEG and drug molecules in water solutions. By integrating the findings from the multi-scale simulations, a comprehensive picture of the unbound and bound states of PEG and drug systems were obtained. This information is valuable for understanding the molecular mechanisms governing the binding of drugs in PEG-based delivery platforms, and it contributes to the rational design and optimization of these systems.