Water-insoluble Drugs Research Articles

Drug release kinetics from in-situ modulated agar/chitosan-bacterial cellulose patches for differently soluble drugs.

Bacterial cellulose (BC) stands out as a promising candidate for novel drug delivery systems due to its micro-mesoporous nanofibrous interconnected structure. However, its performance is limited by the burst release of hydrophilic drugs and lower incorporation of the less water-soluble or insoluble drugs. In this study, we explored its potential as a drug carrier for two distinct types of drugs: Diclofenac sodium and Simvastatin, representing water-soluble and water insoluble compounds, respectively. To tune the morphology and drug-BC interaction, agar and chitosan were introduced into the culture medium during BC synthesis for in-situ modification. These modulated BCs are characterized and further analyzed through drug release studies and mathematical modeling to understand the mechanisms and key factors controlling the drug release behavior. Incorporating agar and chitosan into the BC network results in changes to its microstructure and crystallinity, which in turn affects the overall swelling, drug loading and release properties. Our results revealed that the BC followed a first-order quasi-Fickian kinetics for water-soluble drug and non-Fickian release mechanism for water-insoluble drug. In contrast, agar-modulated BC (A-MBC) demonstrated a non-Fickian first-order diffusion kinetics, with slow release for water-soluble drug and sustained release for the water-insoluble drug due to the higher density which impedes drug release. Chitosan-modulated BC (C-MBC) exhibited non-Fickian first-order kinetics, with slower release for water soluble drug. Further, C-MBC exhibited extended release for water insoluble drug to over 14 days, following first-order kinetics for the first 12 h, then transitioning to zero-order kinetics with a Case II release mechanism, attributed to drug-matrix interactions. These findings successfully demonstrate the possibility to tailor BC thus the release kinetics for both water-soluble and less soluble or insoluble drugs.

Lipid-Based Nanoformulations for Drug Delivery: An Ongoing Perspective

Oils and lipids help make water-insoluble drugs soluble by dispersing them in an aqueous medium with the help of a surfactant and enabling their absorption across the gut barrier. The emergence of microemulsions (thermodynamically stable), nanoemulsions (kinetically stable), and self-emulsifying drug delivery systems added unique characteristics that make them suitable for prolonged storage and controlled release. In the 1990s, solid-phase lipids were introduced to reduce drug leakage from nanoparticles and prolong drug release. Manipulating the structure of emulsions and solid lipid nanoparticles has enabled multifunctional nanoparticles and the loading of therapeutic macromolecules such as proteins, nucleic acid, vaccines, etc. Phospholipids and surfactants with a well-defined polar head and carbon chain have been used to prepare bilayer vesicles known as liposomes and niosomes, respectively. The increasing knowledge of targeting ligands and external factors to gain control over pharmacokinetics and the ever-increasing number of synthetic lipids are expected to make lipid nanoparticles and vesicular systems a preferred choice for the encapsulation and targeted delivery of therapeutic agents. This review discusses different lipids and oil-based nanoparticulate systems for the delivery of water-insoluble drugs. The salient features of each system are highlighted, and special emphasis is given to studies that compare them.

CONSIDERING DIMETHYL SULFOXIDE SOLVENT TOXICITY TO MAMMALIAN CELLS AND ITS BIOLOGICAL EFFECTS.

Dimethyl sulfoxide (DMSO) is a common solvent in biological and medical research for dissolving water-insoluble compounds and drugs. However, the impact of DMSO goes beyond its primary function. High-throughput and in vitro assays have uncovered various effects of DMSO in mammalian cells. The present article highlights the biological effects of DMSO on normal and cancerous mammalian cells.

Bulking up: the impact of polymer sterics on emulsion stability.

Encapsulation of hydrophobic active ingredients is critical for targeted drug delivery as water-insoluble drugs dominate the pharmaceutical marketplace. We previously demonstrated hexadecane-in-water emulsions stabilized with a pH-tunable polymer, poly(acrylic acid) (PAA), via a steric layer preventing particle aggregation. Using vibrational sum frequency scattering spectroscopy (VSFSS), here we probe the influence of steric hindrance on emulsion colloidal stability by tailoring the molecular weight of PAA and by adding an additional methyl group to the polymer backbone via poly(methacrylic acid) (PMAA) at pH 2, 4, and 6. At low polymer molecular weight (2 and 10 kDa), PAA adsorption is entropy driven and akin to surfactant-mediated stabilization. With 450 kDa PAA, the longer polymer chain emphasizes enthalpically favored polymer-oil interactions to initially coat the surface, and forms layers at increasing molecular weight (1000 and 4000 kDa). PMAA exhibits better oil-solubility than PAA at low concentrations but cannot accommodate the steric hindrance at higher concentrations leading to disorder. Finally, we connect our molecular-level understanding of PAA ordering with temperature-dependent dynamic light scattering experiments and observe that emulsions coated with PAA at pH 2 and 4 maintain colloidal stability from 0-90 °C, making PAA a promising polymer for hydrophobic drug delivery.

Spectrophotometric quantification of trace levels of cyanide in water-insoluble drug substances and confirmation of specificity through an orthogonal comparison approach

Some pharmaceutical ingredients use cyanide in their synthesis, and this impurity must be controlled as per ICH, FDA and EDQM regulatory compliance. Spectrophotometric approaches for measuring cyanide levels are confined to water or water-soluble compounds with poor solution stability and low sensitivity. No method is available for the cyanide in water-insoluble drug substances through spectrophotometry. To address this gap, our study proposed a spectrophotometric approach for measuring trace cyanide in water-insoluble drugs such as Primidone and Clobazam. This method utilizes chloramine-T, which reacts with cyanide to form cyanogen chloride (CNCl), consequently reacting with pyridine-barbituric acid to produce a coloured derivative (C13H10N4O6, MW: 318.06 g/mol). This protocol also involves the selection of a suitable solvent and optimizing the pH for sensitive/accurate quantification of cyanide impurity. Mass spectrometry confirms cyanide derivatization as part of the orthogonal procedure comparison of ICH Q2 (R2). Method validation follows ICH Q2 (R2) guidelines in determining specificity, LOD (0.396 ppm), LOQ (1.200 ppm), linearity (1.2-45 ppm), and recovery (91-99% with %RSD<10%) of the method. The stability of the pyridine-barbituric acid reagent and derivatized compound was also evaluated. This approach effectively measures cyanide in water-insoluble drugs, meeting essential regulatory standards.

Advancements in Micellar Formulation: Drug Delivery Vehicle for Water-Insoluble Drugs

: Micellar systems, particularly polymeric micelles, have emerged as a promising drug delivery vehicle for water-insoluble compounds. Polymeric micelles, self-assembled nanostructures made from amphiphilic block copolymers, have emerged as a promising drug delivery vehicle for water-insoluble compounds. These micelles offer high drug loading capacity, stability, and the ability to solubilize large amounts of hydrophobic drugs, making them an attractive option for delivering drugs with limited solubility and bioavailability. Their small size allows for efficient delivery and targeting of specific tissues or cells, reducing off-target effects and improving therapeutic outcomes. This review provides a brief overview of drug delivery system challenges, solutions, techniques of micelle formation, factors affecting micelle stability and drug loading, applications, pharmacokinetics and pharmacodynamics of micellar formulations, toxicological considerations, limitations, recent advancements, and clinical trials of micelles in drug delivery. By addressing these key aspects, this review seeks to provide a comprehensive understanding of the current status and prospects of polymeric micelles as a promising drug delivery system.

Formulation and evaluation of salicylic acid hydrogel based on hydrotropic solubility enhancement technique

Background and objective: Salicylic acid (SA) has keratolytic activities and it is used topically to treat dandruff and seborrheic dermatitis. The hydrotropic phenomenon in pharmaceutical preparations is utilized to enhance the solubility of water-insoluble drug molecules that promoted to prepare the salicylic acid as a hair gel for local effect and it can extend its keratolytic action for a longer period compared to the salicylic acid solution. Methods: Preformulation study was performed to exclude any unwanted chemical interaction between SA and excipients using Fourier-transform infrared spectroscopy (FTIR). The solubility of SA was determined separately in sodium acetate and sodium citrate solutions at a concentration of 1, 3, and 5 %w/v, using distilled water as a solvent. An optimum gel formulation was developed and it was used to prepare the SA gel formulation. Characterizations were performed in terms of physical appearance, viscosity, pH, and spreadability, in-vitro studies were performed in physiological pH, and ex-vivo diffusion studies were performed utilizing rats’ skin. Results: FTIR did not show any chemical interaction between the drug and sodium citrate. The hydrotropic solution of sodium citrate with a concentration of 5% w/v increased the solubility of SA by 28 folds, while the sodium acetate solutions with a concentration of 5% w/v increased the solubility of SA by 19 folds. The optimum gel formula (F1) with a drug content of 97% showed a slow dissolution rate and minimum diffusion through the skin. Conclusion: The hydrotropic solubilization technique significantly influenced the solubilization of salicylic acid in the water and the highest solubility rate was achieved from 5% w/v sodium citrate solution. The formulated hydrogels using carbopol 971P as gelling agent decreased the diffusion rate of SA.

Low concentration dimethyl sulfoxide (DMSO) modulates epileptiform synchronization in the 4-aminopyridine in vitro model

Dimethyl sulfoxide (DMSO) is commonly used to dissolve water-insoluble drugs due to its dipolar and aprotic properties. It also serves as a vehicle in many pharmacological studies. However, it has been reported that DMSO can induce seizures in human patients, lower seizure threshold in vivo, and modulate ion receptors activities in vitro. Therefore, we investigated here the effect of 0.03 % and 0.06 % DMSO, which are 10–50 times lower than what usually employed in previous studies, in the 4-aminopyridine (4AP) model of epileptiform synchronization in male mouse brain slices. We found that 0.03 % and 0.06 % DMSO increase 4AP-induced ictal discharge rate, while 0.06 % DMSO decreases ictal discharge duration. Our results suggest that the effects of DMSO on neuronal excitability deserve further analysis and that investigators need to be aware of its confounding effect as a solvent, even at very low concentrations.

Refined tamoxifen administration in mice by encouraging voluntary consumption of palatable formulations

Drug administration in preclinical rodent models is essential for research and the development of novel therapies. Compassionate administration methods have been developed, but these are mostly incompatible with water-insoluble drugs such as tamoxifen or do not allow for precise timing or dosing of the drugs. For more than two decades, tamoxifen has been administered by oral gavage or injection to CreERT2–loxP gene-modified mouse models to spatiotemporally control gene expression, with the numbers of such inducible models steadily increasing in recent years. Animal-friendly procedures for accurately administering tamoxifen or other water-insoluble drugs would, therefore, have an important impact on animal welfare. On the basis of a previously published micropipette feeding protocol, we developed palatable formulations to encourage voluntary consumption of tamoxifen. We evaluated the acceptance of the new formulations by mice during training and treatment and assessed the efficacy of tamoxifen-mediated induction of CreERT2–loxP-dependent reporter genes. Both sweetened milk and syrup-based formulations encouraged mice to consume tamoxifen voluntarily, but only sweetened milk formulations were statistically noninferior to oral gavage or intraperitoneal injections in inducing CreERT2-mediated gene expression. Serum concentrations of tamoxifen metabolites, quantified using an in-house-developed cell assay, confirmed the lower efficacy of syrup- as compared to sweetened milk-based formulations. We found dosing with a micropipette to be more accurate than oral gavage or injection, with the added advantage that the method requires little training for the experimenter. The new palatable solutions encourage voluntary consumption of tamoxifen without loss of efficacy compared to oral gavage or injections and thus represent a refined administration method.

Phytofabricated ZnO-NPs mediated by Hibiscus tiliaceus leaf extract and its potential as a diosgenin delivery vehicle.

Zinc oxide nanoparticles (ZnO-NPs) have provided promising potential in the biomedical field, including the ability to overcome various health problems. Diosgenin is used to treat multiple health disorders but has very low solubility in water. Using ZnO-NPs as a diosgenin delivery vehicle was expected to increase the solubility of diosgenin, which would affect its bioavailability. This study demonstrates phytofabrication and characterization of ZnO-NPs, loading of diosgenin onto the ZnO-NPs, characterization of the product (ZnO-NPs/diosgenin), and evaluations of diosgenin release. Phytofabrication of the ZnO-NPs was carried out with zinc precursors and Hibiscus tiliaceus leaf extract (HLE) obtained with various extraction solvents. To explore the potential of using the ZnO-NPs as a diosgenin delivery vehicle, diosgenin release from the ZnO-NPs/diosgenin was studied. Based on the X-ray fluorescence (XRF) and X-ray diffraction (XRD) results, ZnO-NPs with high purity have been successfully fabricated. Nano-sized particles were detected using scanning electron microscopy (SEM) and confirmed by transmission electron microscopy (TEM), revealing the smallest particle size of 45.924 ± 27.910 nm obtained from the methanol extract with the zinc acetate precursor. The ZnO-NPs had hexagonal wurtzite and rod-like structures. Diosgenin was successfully added to the ZnO-NPs with loadings of 79.972% for ZnO-HLMEA-D500 (ZnO-NPs/diosgenin produced by doping with a 500 μg mL-1 of diosgenin solution) and 39.775% for ZnO-HLMEA-D1000 (ZnO-NPs/diosgenin produced by doping with a 1000 μg mL-1 of diosgenin solution). The solubilities of diosgenin from ZnO-HLMEA-D500 and ZnO-HLMEA-D1000 were higher than that of free diosgenin, confirming that ZnO-NPs have potential as delivery vehicles for diosgenin and conceivably other water-insoluble drugs.

Solubility and Dissolution Enhancement of Rosuvastatin Calcium by Using HPMC &amp; Guar Gum Polymers and Formulated into Capsule Dosage Form

The main objective of the current study was to prepare the solid dispersions of Rosuvastatin calcium and formulated into capsule dosage form with the combination of different polymers. Solid dispersions are prepared by fusion method by using combination of polymers in different concentrations such as HPMC and Guar gum. Solid dispersion technique will be selected as an efficient means for improving the solubility, dissolution rate and improves the bioavailability of water insoluble drugs. Solid dispersion of Rosuvastatin by the above mentioned method increases the dissolution rate of Rosuvastatin. These solid dispersions will be evaluated by parameters such as drug content, solubility, X-RD, percentage yield, DSC and in-vitro dissolution profile. The stability study of the formulations as per ICH guideline Q1A in stability chamber both at intermediate and accelerated conditions ascertained that the formulations are stable at wide range of storage conditions.

Platelet Membrane-Coated Curcumin-PLGA Nanoparticles Promote Astrocyte-Neuron Transdifferentiation for Intracerebral Hemorrhage Treatment.

Intracerebral hemorrhage (ICH) is a hemorrhagic disease with high mortality and disability rates. Curcumin is a promising drug for ICH treatment due to its multiple biological activities, but its application is limited by its poor watersolubility and instability. Herein, platelet membrane-coated curcumin polylactic-co-glycolic acid (PLGA) nanoparticles (PCNPs) are prepared to achieve significantly improved solubility, stability, and sustained release of curcumin. Fourier transform infrared spectra and X-ray diffraction assays indicate good encapsulation of curcumin within nanoparticles. Moreover, it is revealed for the first time that curcumin-loaded nanoparticles can not only suppress hemin-induced astrocyte proliferation but also induce astrocytes into neuron-like cells in vitro. PCNPs are used to treat rat ICH by tail vein injection, using in situ administration as control. The results show that PCNPs are more effective than curcumin-PLGA nanoparticles in concentrating on hemorrhagic lesions, inhibiting inflammation, suppressing astrogliosis, promoting neurogenesis, and improving motor functions. The treatment efficacy of intravenously administered PCNPs is comparable to that of in situ administration, indicating a good targeting effect of PCNPs on the hemorrhage site. This study provides a potent treatment for hemorrhagic injuries and a promising solution for efficient delivery of water-insoluble drugs using composite materials of macromolecules and cell membranes.

The Controlled Preparation of a Carrier-Free Nanoparticulate Formulation Composed of Curcumin and Piperine Using High-Gravity Technology.

Carrier-free nanoparticulate formulations are an advantageous platform for the oral administration of insoluble drugs with the expectation of improving their bioavailability. However, the key limitation of exploiting carrier-free nanoparticulate formulations is the controlled preparation of drug nanoparticles on the basis of rational prescription design. In the following study, we used curcumin (Cur) and piperine (Pip) as model water-insoluble drugs and developed a new method for the controlled preparation of carrier-free drug nanoparticles via multidrug co-assembly in a high-gravity environment. Encouraged by the controlled regulation of the nucleation and crystal growth rate of high-gravity technology accomplished by a rotating packed bed, co-amorphous Cur-Pip co-assembled multidrug nanoparticles with a uniform particle size of 130 nm were successfully prepared, exhibiting significantly enhanced dissolution performance and in vitro cytotoxicity. Moreover, the hydrogen bonding interactions between Cur and Pip in nanoparticles provide them with excellent re-dispersibility and storage stability. Moreover, the oral bioavailability of Cur was dramatically enhanced as a result of the smaller particle size of the co-assembled nanoparticles and the effective metabolic inhibitory effect of Pip. The present study provides a controlled approach to preparing a carrier-free nanoparticulate formulation through a multidrug co-assembly process in the high-gravity field to improve the oral bioavailability of insoluble drugs.

Cocrystal Prediction of Nifedipine Based on the Graph Neural Network and Molecular Electrostatic Potential Surface.

Nifedipine (NIF) is a dihydropyridine calcium channel blocker primarily used to treat conditions such as hypertension and angina. However, its low solubility and low bioavailability limit its effectiveness in clinical practice. Here, we developed a cocrystal prediction model based on Graph Neural Networks (CocrystalGNN) for the screening of cocrystals with NIF. And scoring 50 coformers using CocrystalGNN. To validate the reliability of the model, we used another prediction method, Molecular Electrostatic Potential Surface (MEPS), to verify the prediction results. Subsequently, we performed a second validation using experiments. The results indicate that our model achieved high performance. Ultimately, cocrystals of NIF were successfully obtained and all cocrystals exhibited better solubility and dissolution characteristics compared to the parent drug. This study lays a solid foundation for combining virtual prediction with experimental screening to discover novel water-insoluble drug cocrystals.

Designing of fucosylated dendrimers as a biocompatible carrier for the targeted delivery of chrysin to human lung cancer cells

Dendrimers, a polymeric macromolecule, have been explored for improving the solubility of water-insoluble drugs, and PAMAM is the most explored dendrimer in nanomedicine. But amine-terminated PAMAM dendrimers confer toxicity to healthy cells. Chrysin (CRY) is a plant-derived phenolic component with anticancer properties and has emerged as a safer drug for the treatment of various cancers, including lung cancer. However, its limited aqueous solubility and poor in vivo stability are the major hurdles to its development as a potential anticancer molecule. In the present work, generation 4 PAMAM dendrimers were functionalized with fucose to overcome the toxicity of dendrimers, enhance the aqueous solubility of CRY, and improve drug targeting to cancer cells. The prepared CRY-loaded fucosylated PAMAM dendrimers (CRY-FUC-PAMAM) were found to have high aqueous solubility and sustained drug release. In the in-vitro studies, CRY-FUC-PAMAM showed improved cytotoxicity with a lower IC50 value at both 24 h and 48 h (1.8 μg/mL and 0.7 μg/mL, respectively), resulting from increased apoptosis and cellular uptake of FUC-PAMAM in A549 human lung cancer cells in comparison to free CRY, whereas FUC-PAMAM was found to be non-toxic. Overall, this biocompatible fucosylated dendrimer could be used as a nanocarrier for the delivery of CRY as a targeted nanomedicine for lung cancer.

Anti-Inflammatory Potential of Beclometasone-Loaded Filomicelles on Activated Human Monocytes.

Polymeric micelles with a hydrophobic core represent versatile nanostructures for encapsulation and delivery of water-insoluble drugs. Here, water-insoluble beclometasone dipropionate (BDP) which is a potent anti-inflammatory therapeutic agent but limited to topical applications so far, is encapsulated. Therefore, this work used an amphiphilic block copolymer self-assembling into flexible polymeric filomicelles, which have recently proven to selectively target inflamed areas in patients with inflammatory bowel disease (IBD). The small diameter and flexibility of these filomicelles is considered beneficial for transepithelial passages, while their length minimizes the unspecific uptake into nontargeted cells. This work successfully establishes a protocol to load the water-insoluble BDP into the core of the filomicelles, while maintaining the particle stability to prevent any premature drug release. The anti-inflammatory efficacy of BDP-loaded filomicelles is further investigated on lipopolysaccharide (LPS) stimulated human monocytes. In these ex vivo assays, the BDP-loaded filomicelles significantly reduce TNF-α, IL-6, IL-1ß, IL-12p70, IL-17a, and IL-23 release after 24 h. Additional time course study of drug-loaded filomicelles and their comparison with a common water-soluble and unspecific corticosteroid demonstratepromising results with significant immune response suppression in stimulated monocytes after 2 and 6 h. These findings demonstrate the potential of polymeric filomicelles as a vehicle for potent water-insoluble corticosteroids.

Development and characterization of dexamethasone nanodispersion for the effective treatment of diabetic retinopathy

Diabetic retinopathy is the most common complication of diabetes and remains the leading cause of vision loss worldwide. The potent glucocorticoid based anti-inflammatory drug dexamethasone (DEX) chosen for the present work is long-acting with half-life of 37–72 h extensively metabolized in to 6-hydroxy-dexamethasone (6-OH-DEX). The present work aimed to develop dexamethasone loaded nanodispersion (DEX-ND) by improving its solubility, half-life, and bioavailability in biological system thereby this formulation may be afforded economically. With the concept that polymeric surfactant improves the solubility of challenging water insoluble drug the present work has been hypothesized to improve its solubility using polyvinyl pyrrolidone (PVP-K30) polymer and polysorbate 80 (Tween 80) hydrophilic non-ionic surfactant, thereby the bioavailability is expected to get enhanced. By varying the PVP K30 and Tween 80 concentrations three different formulations were developed. The developed DEX-ND was further characterized for its compatibility, particle size, zeta potential, morphology, and in vitro release behavior. The results of Fourier transform infrared spectrometric analysis indicate the compatibility nature of DEX-ND along with other excipients/drug used in the formulation. The developed formulations showed spherical morphology, particle size ranging from 550.46 ± 107.82 to 3560 ± 284.29 nm, zeta potential ranging from −29.23 ± 1.09 to −7.793 ± 1.01 mV. The amount of DEX present in the DEX-NDs was found to be 0.95–3.93 mg. The in vitro release studies as performed by dialysis bag method showed a sustained release pattern. The results of ex vivo corneal permeation studies indicates that the developed DEX- NDs has some exposure to the posterior segment of the eye.

Conversion of iota carrageenan hydrocolloids to hydrophobic hydrocolloids, by the replacement of potassium to barium ion, for the entrapment of water insoluble drugs

To entrap the water-insoluble medicine, the current innovation provides a cost-effective solution to the increasing need for hydrophobic gel. Improving the bioavailability of a medicine that is poorly soluble begins with entrapping the substance. By only switching out the monovalent ions for divalent ones, the researchers hope to increase the hydrophobicity of their material. In this experiment, barium ions were used instead of potassium ions in the iota carrageenan to make structural, chemical, and physicochemical changes easier during transformation. Hydrophobicity was determined qualitatively by observing the ability to trap small oil particles and repel water, moreover, the quantitative investigation was carried out using the weight loss method to determine the metal ion water isolation value and drug entrapment value within the core of barium linked carrageenan gel. The metal’s weight loss metal water affinity was determined to be 90% after 24 h, but it was only 67% with the synthesized gel coating the metal, this clearly shows that the barium gel had greater water protection activity. Furthermore, the barium-linked gel exhibited three times the entrapment capacity of the parent gel, and it successfully encased the water-insoluble medication with controlled release. The current study shows how the attached ion to the polymer changes its hydrophilic behavior into a hydrophobic one. This is a new and inexpensive way to do things. However, up until this point, the addition of the hydrophobic substrate and the functionalization of the polymer have been utilized. This leads to a plan that shows promise for improving the ability of hydrophobic hydrocolloid gels to hold drugs that do not dissolve in water.

Multifunctional organohydrogels for on-demand controlled drug release

Controlled drug release has sparked much attention in the field of drug delivery by prolonging the duration of drug effectiveness and reducing drug toxicity. However, the development of controlled-release drug delivery systems remains a significant challenge, primarily due to inadequate drug compatibility, low biocompatibility, and low response sensitivity of the drug carriers. Herein, an innovative strategy for fabricating multifunctional organohydrogels as drug carrier systems is designed. 1-Tetradecanol/water emulsions, stabilized by cellulose acetoacetate (CAA), are initially prepared. The organohydrogels are fabricated by the ternary enzyme-mediated polymerization of the monomer- containing emulsion. The amphipathy of CAA ensures the stability of emulsions during polymerization, and CAA participates in polymerization as an initiator. Through the reversible crystallization-melting transition of 1-tetradecanol, the drug can be encapsulated in/released from the organohydrogel. Moreover, 1-tetradecanol enhances the bioavailability of water-insoluble drugs without any additional cosolvent. Therefore, biofriendly organohydrogels can serve as ideal dressings with adjustable mechanical properties, effective temperature regulation, and temperature-triggered drug release ability.

Revolutionizing Knee Osteoarthritis Treatment: Innovative Self-Nano-Emulsifying Polyethylene Glycol Organogel of Curcumin for Effective Topical Delivery.

In the current study, self-nano-emulsifying (SNE) physically cross-linked polyethylene glycol (PEG) organogel (SNE-POG) as an innovative hybrid system was fabricated for topical delivery of water-insoluble and unstable bioactive compound curcumin (CUR). Response surface methodology (RSM) based on Optimal Design was utilized to evaluate the formulation factors. Solid fiber mechanism with homogenization was used to prepare formulations. Pharmaceutical evaluation including rheological and texture analysis, their mathematical correlations besides physical and chemical stability experiments, DSC study, in vitro release, skin permeation behavior, and clinical evaluation were carried out to characterize and optimize the SNE-OGs. PEG 4000 as the main organogelator, Poloxamer 188 (Plx188) and Ethyl Cellulose (EC) as co-gelator/nanoemulsifier agents, and PEG 400 and glycerin as solvent/co-emulsifier agents could generate SNE-POGs in PS range of 356 to 1410 nm that indicated organic base percentage and PEG 4000 were the most detrimental variables. The optimized OG maintained CUR stable in room and accelerated temperatures and could release CUR sustainably up to 72 h achieving high flux of CUR through guinea pig skin. A double-blind clinical trial confirmed that pain scores, stiffness, and difficulty with physical function were remarkably diminished at the end of 8 weeks compared to the placebo (71.68% vs. 7.03%, 62.40% vs. 21.44%, and 45.54% vs. 8.66%, respectively) indicating very high efficiency of system for treating knee osteoarthritis. SNE-POGs show great potential as a new topical drug delivery system for water-insoluble and unstable drugs like CUR that could offer a safe and effective alternative to conventional topical drug delivery system.