Due to their broad spectrum of biological activities and attractive pharmacological properties, flavonoids are very promising molecules for application in skin care products. In this study, phloridzin and naringin medium- and long-chain fatty acid esters were enzymatically synthesized in reaction with natural oils (coconut and linseed oil) and transdermal delivery of synthesized esters through artificial Strat-M membrane was investigated. Experimental results were succesfully fitted using Peppas and Sahlin model which includes the phase. Release kinetics of all examined flavonoid esters from gel emulsions through the membrane depended on both diffusion and polymer relaxation effect (0.5< < 1). The estimated effective diffusion coefficients ranged from 0.168·10 to 6.149·10 cm s for phloridzin esters and from 0.116·10 to 4.210·10 cm s for naringin esters. The effective diffusion coefficients decreased with the increase in ester molecular weight indicating the size-dependent diffusion. All formulation showed good stability, excellent hydration effect, and excellent dermatological compatibility without irritating effect. It can be concluded that gel emulsions with a mixture of flavonoid esters enzymatically synthesized in reaction with vegetable oils can be effectively topically applied as a skin care products.

Polymeric micelles were prepared for the delivery of donepezil, a leading Alzheimer's disease drug, to enhance its transport across the blood-brain barrier (BBB). Poly(ethylene glycol)--poly(-butyl methacrylate) amphiphilic block copolymers were synthesized reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers were characterized by gel permeation chromatography and nuclear magnetic resonance spectroscopy. Empty and donepezil loaded polymer micelles were formed using the dialysis method and characterized by dynamic light scattering and transmission electron microscopy. Drug loading efficiency and release behavior were monitored using UV/Vis spectroscopy, and cytotoxicity was evaluated colorimetric tests and impedance measurements. Additionally, the permeability of the nanocarriers across an BBB culture model was assessed. Drug-loaded micelles demonstrated similar permeability to free donepezil but offered sustained release and improved stability. This micellar delivery system holds significant potential for improving therapeutic outcomes in Alzheimer's treatment by enhancing donepezil's delivery across the BBB. Improved BBB permeability and sustained drug release could lead to more effective concentration of the drug in the brain, potentially reducing peripheral cholinergic side effects, such as nausea and vomiting, often observed with traditional donepezil administration. This could result in better patient compliance and improved cognitive outcomes, making this nanocarrier system a promising alternative for Alzheimer's therapy.

This work aimed to develop fenbendazole nanocrystals to evaluate their effects on the energetic metabolism of cysticerci, following an intracranial inoculation in mice.

This study aimed to provide an alternative and effective delivery system to combat polymyxin B (PMB) toxicity and bacterial resistance through inhalation therapy. PMB was formulated as liposomal dry powder for inhalation using thin-film hydration and spray-dried methods. PMB formulations were characterized physically. The aerodynamic properties were determined using next-generation impactor (NGI). drug release was done in a phosphate buffer pH 7.4 for 2 h. Cytotoxicity was evaluated by the MTT cell viability assay. Antimicrobiological activities were done using bioassay and flow cytometry. Particle sizes of the spay-dried formulations were between 259.83 ± 9.91 and 518.73 ± 27.08 nm while the zeta potentials ranged between 3.07 ± 0.27 and 4.323 ± 0.36 mV. The Fourier-transform infrared spectroscopy shows no interaction between PMB and other excipients. Differential scanning calorimetry thermograms revealed amorphousness of the formulated powders and SEM revealed spherical PMB formulations. Similarly, mass media aerodynamic diameter results were 1.72-2.75 nm, and FPF was 25%-26%. The cumulative release of the PMB formulations was 90.3 ± 0.6% within 2 h. The killing kinetics revealed total cell death at 12 and 24 h for and , respectively. The PMB inhalation liposome showed better activity and was safe for lung-associated cell lines.

Povidone-iodine (PVP-I) is widely used as an antiseptic in medical applications. However, its effectiveness is limited by certain drawbacks, such as low solubility in water and high volatility. Therefore, a formulation of a stable solid PVP-I is desirable. In this study, complexes of molecular PVP-I with polyethylene glycol-polyvinyl alcohol copolymer (PEG-PVA copolymer) were considered water-soluble iodophors. Two different methods were used to prepare the solids: physical mixtures and kneading. The physical characteristics of the obtained solids were evaluated using several spectroscopic methods. The presence of iodine was confirmed by a potentiometric titration and antimicrobial activity was tested. The results showed that the PEG-PVA copolymer interacted with povidone primarily through hydrogen bonding between the hydroxyl part of the PEG-PVA copolymer and the amide part of povidone with an estimated binding energy of 3.2 kcal/mol. The amide groups polarity in povidone made them more likely to form hydrogen bonds with the PEG-PVA copolymer. Also, the protonated pyrrolidone bonded to the triiodide anions by intermolecular hydrogen bonds, which increased PVP-I solubility in water. The kneading method provided a faster dissolution rate than physical mixing and pure PVP-I. The iodine contents were within an acceptable range (10-12%), and the antimicrobial activity proved effective against , , and .

Exendin-4 (ex-4) is a peptide molecule that regulates blood glucose levels without causing hypoglycemia by providing insulin secretion from beta cells in the pancreas. Self-nanoemulsifying drug delivery systems (SNEDDS) attract attention for oral administration of therapeutic peptide/proteins because they protect therapeutic peptide/proteins from the gastric environment, reduce changes due to food effects, are easy to prepare and scale-up. Ex-4 has no commercial form that can be administered orally. In this study, the cytotoxicity, cellular uptake, and insulin secretion of ex-4 and ex-4/chymostatin (chym) SNEDDS were investigated on INS-1E rat pancreatic beta cells. The effect of ex-4 and ex-4/chym SNEDDS on cell viability in INS-1E cells increased when the dilution ratio higher. Ex-4 and ex-4/chym SNEDDS increased insulin levels in 2.8 mM (low-dose) glucose-induced INS-1E cells 2.21-fold and 2.17-fold compared to control, respectively. Ex-4 and ex-4/chym SNEDDS increased insulin levels in 16.7 mM (high dose) glucose-induced INS-1E cells compared to control, respectively. In cellular uptake studies, coumarin-6 solution penetrated the apical membrane of INS-1E cells and remained in the cytoplasm, while coumarin-6 loaded SNEDDS were visualized in the nuclei of the cell. These findings will likely be useful in the development of new formulations for the oral administration of peptides/proteins.

Deep eutectic solvents (DESs) are green alternatives to ionic liquids with wide applications in organic synthesis and catalysis. DESs are characterized by being easily prepared, biodegradable, nontoxic, and noninflammable. When one or more of the DES components is active pharmaceutical ingredient (API), the eutectic mixtures are named as therapeutic deep eutectic solvents (THEDESs). THEDESs are prepared in order to improve the solubility and/or the permeability of the APIs. This review presents a brief summary of the most important THEDESs reported to date having antimicrobial and/or anticancer activities. The challenges and limitations of THEDES preparation were also discussed. The work presented here indicated the importance of THEDES as a promising drug delivery system that can overcome the bioavailability problems while retaining or enhancing the biological activity of its components.

Formononetin (FNT) has limited application due to poor water solubility and substantial phase II metabolism. In the present study, we used phospholipid complex (PC) containing FNT and UDP-glucuronosyltransferase (UGT1A1) inhibitor piperine (PIP) to overcome FNT limitations. We characterized and compared both FNT-PC and FNT-PIP-PC complexes. Our data showed both groups improved FNT water solubility and oil-water partition coefficient. NMR, DSC, and SEM were performed to identify the interaction and the geometrical nature of complex. When compared, FNT-PIP-PC released more FNT in release and permeation through Caco-2 monolayer than FNT-PC and pure FNT. data was consistent with the pharmacokinetic profile that showed increased, C and AUC by 7.16 and 23.33-fold and 29.65 and 23.33-fold at 5 and 10 mg/kg in FNT-PIP-PC, compared to pure FNT. Additionally, co-treatment of PIP and FNT improved pharmacological action in dexamethasone-induced osteoporosis. Thus, our study showed addition of PIP in FNT-PC further increases FNT water solubility and protects it from phase II metabolism, leading to enhanced bioavailability with improved pharmacological activity.

The present study evaluates the sticking propensity of Uncoated steel, and chromium nitride (CrN), zirconium nitride (ZrN), titanium nitride (TiN) and Ultracoat punch coatings during the tableting process of microcrystalline cellulose (MCC) conducted on a Manesty F3 single station tableting press.

Traditional chemotherapeutic drugs lack optimal efficacy and invoke severe adverse effects in cancer patients. Polydatin (PD), a phytomedicine, has gradually gained attention due to its antitumor activity. However, its low solubility and poor bioavailability are still cornerstone issues. The present study aimed to fabricate and develop hyaluronic acid/lactoferrin-double coated PD/PLGA nanoparticles a layer-by-layer self-assembly technique for active targeting of CD44 receptors in lung cancer. Different molecular weights (M.wt.) of HA (32 and 110 kDa) were exploited to study the relationship between the HA M.wt. and the NPs targeting efficacy. The optimized formulations were fully characterized. Their cytotoxicity and cellular uptake were investigated against A549 cell line by CCK-8 kit and fluorescence imaging, respectively. Finally, HA110/Lf-coated PD/PLGA NPs (F9) were subjected to a competitive inhibition study to prove internalization through CD44 overexpressed receptors. The results verified the fabrication of F9 with a particle size of 174.87 ± 3.97 nm and a zeta potential of -24.37 ± 1.19 mV as well as spherical NPs architecture. Importantly, it provoked enhanced cytotoxicity (IC = 0.57 ± 0.02 µg/mL) and superior cellular uptake efficacy. To conclude, the current investigation lays the foundation for the prospective therapeutic avenue of F9 for active targeting of CD44 receptors in lung cancer.

Erectile dysfunction (ED), is a common and multidimensional sexual disorder, which comprises changes among any of the processes of the erectile response such as organic, relational, and psychological. However, both endocrine and nonendocrine causes of ED produce substantial health implications including depression and anxiety due to poor sexual performance, eventually affecting man's life eminence. Marginally invasive interventions following ED consist of lifestyle modifications, oral drugs, injections, vacuum erection devices, etc. Nevertheless, these conventional treatment regimens follow certain drawbacks such as efficacy and safety issues, and navigate to the development of novel therapeutic approaches such as nanomedicine for ED management. Nanotechnology-centred drug delivery platforms are being explored to minimize these limitations with better and effectiveness. Moreover, nanomedicine and nanocarrier-linked approaches are rapidly developing science in the nanoscale range, which contributes to site-specific delivery in a controlled manner and has generated considerable interest prominent to their potential to enhance bioavailability, decrease side effects, and avoidance of first-pass metabolism. This review provides an overview of recent discoveries regarding various nanocarriers and nano-delivery methods, along with current trends in the clinical aspects of ED. Additionally, strategies for clinical translation have been incorporated.

Oral candidiasis is often challenging due to limited effectiveness of topical treatments. This study aimed to develop novel caspofungin formulations for administration onto the oral mucosa to enhance drug retention and efficacy.

Ionic liquids (ILs) are considered salt in liquid state, which is composed of organic cations and anions with low melting points (<100 °C). ILs have become a major scientific area with an extensive range of applications including chemistry, electrochemistry, and pharmaceutics. ILs have received great research interest in the pharmaceutical field as solvents, anti-solvents, co-solvents, and reagents in synthesis and formulation. While therapeutic ILs have been investigated for oral and trans-dermal drug delivery systems showing promising compatibility with a wide range of therapeutics, enhanced drug permeation through the skin, and cell membrane solvation to open channels to facilitate molecular passage, their potential to cross the challenging blood-brain barrier (BBB) remains an unanswered question. IL-based therapies could potentially be a game changer for improving drug delivery to cellular targets both at and across the BBB. In this review, we discuss (1) the tunable physicochemical properties of ILs; (2) the vast and various applications of ILs in the development and improvement of drug delivery systems; and (3) ILs as a potential approach for increasing drug accumulation in the brain tissue.

Asthma and Chronic Obstructive Pulmonary Disease (COPD) are major global health concerns, with inhalation therapy being a primary treatment method. Dry powder inhalers (DPIs) often face challenges related to particle aggregation, which can diminish drug delivery efficiency. This study investigates particle aggregation and aims to optimize the cohesion-adhesion balance to improve inhalation efficiency. Advanced techniques like atomic force microscopy and Raman imaging were used to analyze particle interactions, focusing on lactose ratios, particle morphology, and drug-drug interactions. The therapeutic efficacy of optimized formulations containing budesonide (BUD) and Arformoterol (AFT) was assessed using an asthma model, showing significant improvements in sRAW, neutrophil count, and tidal volume compared to the positive control, with -values below 0.01. AFT exhibited comparable efficacy to Formoterol at half the dose. Additionally, pharmacokinetic studies demonstrated similar in vivo behavior between the drugs, confirming the therapeutic advantage of AFT, with -values for AUC and Cmax of .646 and .153, respectively. The fine particle fractions for AFT and BUD were 39.4% and 50.6%, respectively, indicating improved drug delivery efficiency and potential for better clinical outcomes in asthma and COPD patients.

Erythropoietin (EPO) is a pivotal hormone that regulates red blood cell production, predominantly synthesized by the kidneys and also produced by the liver. Since the introduction of recombinant human EPO (rh-EPO) in 1989 through recombinant DNA technology, the therapeutic landscape for anemia has been improved. rh-EPO's market expansion has been substantial, with its application extending across various conditions such as chronic kidney disease, cancer-related anemia, and other disorders. Despite its success, significant concerns remain regarding the stability of EPO, which is critical for preserving its biological activity and ensuring therapeutic efficacy under diverse environmental conditions. Instability issues, including degradation and loss of biological activity, challenge both drug development and treatment outcomes. Factors contributing to EPO instability include temperature fluctuations, light exposure, and interactions with other substances. To overcome these challenges, pharmaceutical research has focused on developing innovative strategies such as stabilizing agents, advanced formulation techniques, and optimized storage conditions. This review article explores the multifaceted aspects of EPO stability, examining the impact of instability on clinical efficacy and drug development. It also provides a comprehensive review of current stabilization strategies, including the use of excipients, lyophilization, and novel delivery systems.

Microneedles have the potential for minimally invasive drug delivery. However, they are constrained by absence of rapid, scalable fabrication methods to produce intricate arrays and serrations for enhanced adhesion. 3D printing techniques like stereolithography (SLA) are fast, scalable modalities but SLAs require non-degradable and stiff resins. This work attempts to overcome this limitation by utilizing a poly (ethylene glycol diacrylate) (PEGDA, F3) resin and demonstrating its compatibility with a commercial SLA printer. FESEM images showed high printing efficiency of customized bioinks (F3) similar to commercial resins using SLA 3D printer. Mechanical endurance tests of whole MNA showed that MNs array printed from F3 resin (485 ± 5.73 N) required considerably less force than commercial F1 resin (880 ± 32.4 N). Penetration performance of F1 and F3 was found to be 10.8 ± 2.06 N and 0.705 ± 0.03 N. In-vitro degradation study in PBS showed that MNs fabricated from F3 resin exhibited degradation after 7 days, which was not observed with the commercial F1 resin provided by the manufacturer. The histology of porcine skin exhibited formation of triangular pores with pore length of 548 μm and efficient penetration into the deeper dermal layer. In conclusion, PEGDA can be used as for fabricating degradable, serrated solid MNs over commercial resin.

The extent and rate of release of active substances from topical products must be sufficient to ensure their effectiveness, which depends on selecting the most appropriate formulation. This study examined allantoin emulsions and gel formulations. In water-in-oil (W/O) and oil-in-water (O/W) emulsions, the main emulsifier was varied, while the same gelling agent was used in all formulations to test the effects of oil phase presence and emulsifier type on allantoin release, as well as the formulations' rheological and textural characteristics. O/W emulsions exhibited similar release rates and the overall amount released over six hours (11-14.8%), while the highest amount of allantoin (20.9%) was released from the gel formulation. Conversely, the amount of allantoin released from the W/O emulsion (0.77%) was insufficient. Experimental data generally fit best with the Higuchi model kinetics. The formulations demonstrated shear-thinning thixotropic behavior. The greatest deviation from the Newtonian type of flow, with the smallest value of constant n (0.106-0.13) and the largest thixotropic loop area (6602.67-8140 Pas) were shown by O/W emulsions. The W/O emulsion exhibited the highest constant n (0.70) and smaller hysteresis area (991.23 Pas). Firmness and consistency values increased in the order: gel < W/O emulsion  < O/W emulsions. The O/W emulsions showed similarity in microstructure and textural characteristics, likely explaining their similar release behavior.

Drug administration to the central nervous system (CNS) has become a great obstacle because of several biological barriers, such as the blood-brain barrier, therefore, brain targeting insights are a light for scientists to move forward for treating neurogenerative diseases using advanced non-invasive methods. The current demand is to use a potential direct route as the nasal administration to transport drugs into the brain enhancing the BBB permeability and hence, increasing the bioavailability. Interestingly, recent techniques have been implanted in formulating nanocarriers-based therapeutics for targeting and treating ischemic stroke using lipid or polymeric-based materials. Nanoparticulate delivery systems are set as an effective platform for brain targeting as polymeric nanoparticles and polymeric micelles or nanocarriers based on lipids for preventing drug efflux to promote optimal therapeutic medication concentration in the brain-diseased site. In recent years, there has been a notable increase in research publications and ongoing investigations on the utilization of drug-loading nanocarriers for the treatment of diverse CNS diseases. This review comprehensively depicts these dangerous neurological disorders, drug targeting challenges to CNS, and potential contributions as novel intranasal nano-formulations are being used to treat and regulate a variety of neurological diseases.

Amino acids have attracted attention as a potential functional excipient for optimizing biopharmaceutics characteristics of poorly soluble drugs. The amino acids are a diverse class with many functional groups, natural compounds, biocompatible, and low-molecular-weight substances. Two amino acids serine and arginine were investigated with meloxicam. Meloxicam has extremely low solubility; being NSAIDs, gastric upset, and ulcer are common side effects. Solid dispersions were produced by precipitation and physical mixing techniques. The produced combinations underwent dissolution, docking, DSC, FTIR, XRD, solubility, and gastric ulcer formation studies. Docking indicated ion pair/salt formation between the basic amino acid arginine and meloxicam. Both solubility and dissolution rates were increased by up to 3000-fold and 12-fold, respectively. DSC, FTIR an XRD supported these findings. Rats treated with meloxicam showed loss of surface gastric epithelium integrity and ulceration. The animal group received meloxicam: arginine showed intact gastric mucosa with the surface epithelium and gastric glands well organized and nearly similar to the untreated control. Arginine with the guanidine group that was capable of preserving gastric mucosa after repeated administration for 10 days. This study highlighted the role of arginine as a functional excipient that did not only improve solubility and dissolution rates but ameliorated the long-standing gastric side effects attributed to meloxicam.