RSC Pharmaceutics最新文献

Eutectic mixtures are often used in drug design and delivery. Herein, thermodynamic and kinetic analyses of the melting process of S-ketoprofen (KTP)/lidocaine (LDC) mixtures were performed by using differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) measurements to trace the composition and melting process of KTP/LDC mixtures. In the binary solid–liquid phase diagram, a constant melting point of 294 K was observed, which is lower than the theoretical eutectic point of 304 K. It is believed that the hydrogen-bonding interactions between KTP and LDC caused a further decrease in the melting point. Melting at 304 K resulted from a eutectic reaction, whereas melting at 294 K was interpreted as the preliminary melting step. A kinetic analysis of the melting process was made possible by performing singular value decomposition (SVD) on a dataset of the FTIR spectra. The principal component vector indicating the magnitude of the contribution of the preliminary melting step reflects the time change in which the molten KTP signal increases after the molten LDC signal increases, which fits the sequential reaction equation. This confirms the preliminary melting stage at 294 K, as indicated by the binary solid–liquid phase diagram obtained by DSC. The activation energy was determined from the reaction rate constant, and a scenario for forming a eutectic mixture was proposed based on the mole fractions of KTP and LDC.

Fungal infections have been a concern for decades, yet effective and approved antifungal agents are limited. We recently developed a potential method to enhance the antifungal activity of a small chitin-binding domain (LysM) from Pteris ryukyuensis chitinase A (PrChiA) by the site-specific introduction of a palmitoyl (C16) group catalyzed by microbial transglutaminase (MTG). Herein, we attempted the conjugation of a series of lipid–peptide substrates with LysM genetically fused with a C-terminal MTG-reactive Q-tag (LysM-Q) to yield LysM-lipid conjugates (LysM-lipids) with different lengths (LysM-C12, -C14, and -C16) and different numbers of alkyl chains [LysM-(C12)₂, -(C14)₂, and -(C16)₂]. The enzymatic conjugation proceeded smoothly for all LysM-lipids, except for LysM-(C16)₂ because of the low aqueous dispersibility of the hydrophobic (C16)₂ lipid–peptide substrate. The combination of amphotericin B (AmB) with LysM-C14 or LysM-C16 exhibited the highest antifungal performance against Trichoderma viride whereas alterations in the number of alkyl chains were not effective in enhancing the antifungal activity of the LysM-lipids. Fluorescent microscopic analysis showed that the fungal cell wall was stained with C14- and C16-modified LysM-muGFP fusion proteins when combined with AmB, suggesting a suitable lipid length to enhance the antifungal action. All LysM-lipids showed minimum cytotoxicity toward mammalian cells, suggesting that LysM-lipids could be a safe additive in the development of new antifungal formulations.

Carvedilol nanosuspension loaded microneedles patch was formulated and characterized by particle size,  zeta potential, solubility, Transmission Electron Microscopy, X-Ray Diffraction, in-vitro release and in-vivo pharmacokinetic studies A nanosuspension-loaded microneedle patch was successfully prepared and characterized by optical microscopy, scanning electron microscopy, axial fracture force, in vitro dissolution study, % drug content, in vitro drug-release study, ex vivo studies, an in vivo study, and stability studies. The particle size, PDI, and zeta potential of the carvedilol nanosuspension were found to be 179.6 ± 1.15 nm, 0.163 ± 0.01, and −14.2 ± 0.55 mV, respectively. There was a 9.21-fold increase in the saturation solubility of the carvedilol nanosuspension. Nanosuspension-loaded microneedles contained 98.78 ± 0.12% carvedilol. The relative bioavailability of the carvedilol from the microneedle patch was found to be 2.82-fold higher compared to the marketed formulation. The drug release from the microneedles followed zero-order kinetics, which is desirable in the case of transdermal delivery. The stability study indicated that the prepared formulation was stable under the storage conditions used. Thus, the developed transdermal microneedle patch containing the carvedilol nanosuspension seems to be a promising approach to foster greater patient compliance for the management of hypertension.

Glaucoma is a leading cause of irreversible blindness, and controlling intraocular pressure is imperative for good clinical outcomes. It is important to use natural stimuli to trigger the release of the drug when it is linked to a nanoparticle/nanocomposite, particularly in ophthalmic applications to maintain sustained release. Herein the preparation and investigation of biocompatible, mucoadhesive dual drug-loaded chitosan (CS)–graphene quantum dot (GQD) nanocomposites are reported. Drug release from the nanocomposite was controlled by the presence of a natural lacrimal fluid enzyme, lysozyme (Lyz). Lyz is efficient at cleaving the β-1,4 glycosidic linkages of CS, thereby releasing the drug of interest. A biocompatible, fluorescent nanomaterial i.e., GQDs, was employed to track drug loading by using simple photoluminescent spectral studies. The optimized nanocomposite encapsulation efficiencies (EEs) were 94.51% and 74.08% for latanoprost (LP) and timolol (TM) and delivered 32.68% and 66.61% of drugs, respectively, in 72 h. Dual drug delivery through the cleavage of β-1,4 glycosidic linkages of CS in the presence of Lyz was confirmed through ¹H-NMR and FE-SEM studies. An increase in the particle size from 490 nm to 1584 nm in the presence of mucin supports the mucoadhesiveness of the nanocomposite. The in vitro cytocompatibility and live/dead staining assays against human corneal epithelial (HCE) cells showed ≥80% cell viability. Ex vivo tests proved that the nanocomposite was non-irritant, and histopathological studies showed normal growth of blood vessels. Molecular docking studies showed the hydrogen bonding and electrostatic interactions between the drug and CS. Hence the developed nanocomposite could be used as an ocular suspension or nanocomposite for further preclinical studies on glaucoma management.

Invasive fungal infections kill more than 1.7 million and affect over a billion people each year; however, their devastating impact on human health is not widely appreciated and frequently neglected by public health authorities. In 2022, the WHO highlighted the urgent need for efficient diagnostic tests as well as safe and effective new compounds, drugs, and vaccines. Our hypothesis was that the naturally occurring polymer chitosan (CS) could be combined with molecular polyoxometalates (POMs) to produce POM@CS hybrid materials to promote broad-spectrum activity and habilitate synergic effects, which will ultimately help to prevent the appearance of resistances. Here we report the synthesis, characterisation, and antimicrobial activity of POM@CS hydrogels. Spectroscopic (FT-IR & EDS) and electron microscopy (SEM & TEM) techniques revealed the structural composition and morphology of the hybrid materials, whilst dynamic mechanical analysis demonstrated that the mechanical properties of the hydrogels were stable between pH 2 and 10 and were highly resistant to acidic conditions. The POM@CS hydrogels were active against Gram-positive Bacillus subtilis and Gram-negative Escherichia coli bacteria, and proved to completely reduce fungal growth of Aspergillus niger and Cladosporium cladosporioides. Furthermore, the antimicrobial activity of the hydrogels could be enhanced through the inclusion of naturally occurring antimicrobial agents such as eugenol and cinnamaldehyde. Altogether, the development of such surface-active antimicrobial hydrogels pave the way to functional materials that can prevent biofilm formation in health and environmental applications and contribute to reducing the spread of antimicrobial resistance.

Targeting therapeutic agents to the brain to treat central nervous system (CNS) diseases is a major challenge due to the blood–brain barrier (BBB). In this study, an attempt was made to deliver a model drug such as doxorubicin (DOX), to the brain in a mouse model through DOX-Polysorbate 80 (DOX-PS80) conjugates. DOX was successfully conjugated with the non-ionic surfactant Polysorbate 80 (PS80) by carbamate linkage and the conjugate was characterized by different spectroscopic techniques, such as FTIR, UV-Visible and NMR. The DOX conjugation efficacy was found to be 43.69 ± 4.72%. The in vitro cumulative release of DOX from the conjugates was found to be 4.9 ± 0.8% in PBS of pH 7.3 and 3.9 ± 0.6% in simulated cerebrospinal fluid (CSF) of pH 7.3 at the end of 10 days. An in vitro BBB permeability assay was carried out using bEnd.3 cells and DOX-PS80 conjugate showed a 3-fold increase in BBB permeability compared with controls. In vitro cytotoxicity assay using U251 human glioblastoma cells showed an IC₅₀ value of 38.10 μg mL⁻¹ for DOX-PS80. Cell uptake studies revealed that DOX-PS80 was effectively taken up (90%) by the bEnd.3 and U251 cells and localized in cytoplasm at the end of 24 h. Pharmacokinetic parameters for DOX-PS80 were evaluated using in silico studies. Tumor spheroid assay and in vivo experiments in Swiss albino mouse demonstrated the possibility of DOX-PS80 conjugate crossing the BBB and delivering the drug molecules to the target site for treating CNS disorders.

The objective of the present study was to synthesize pH-sensitive gum ghatti-cl-poly (acrylic acid)/GO hydrogels for the drug delivery and controlled combined release of metformin hydrochloride and sodium diclofenac. Gum ghatti (Gg) and acrylic acid (AA) were free radicals copolymerized using N,N‘-methylenebisacrylamide (MBA) and tetramethyl ethylenediamine as cross-linkers and ammonium persulfate (APS) as an initiator. The structure and surface morphology of the composite hydrogel were determined using FTIR and SEM analyses, respectively. The FTIR studies confirmed the successful acrylic acid and graphene oxide grafting and drug binding onto the backbone of the synthesized hydrogel. Drug-release kinetics and mechanisms were investigated using zero- and first-order kinetic models as well as the Korsmeyer–Peppas model, Higuchi model, and Hixson–Crowell model. Drug-release experiments revealed the important characteristics related with physiologically expected pH levels, including a high release rate at pH 9.2. At pH 9.2, metformin HCl drug release increased from 4.68% to 37.46%, whereas sodium diclofenac release increased from 3.25% to 54.75%. However, at pH 9.2, both metformin hydrochloride and sodium diclofenac showed non-Fickian transport mechanisms. In summary, combining drugs may reduce the efficacy of a single medication while influencing metabolic rescue mechanisms.

Ultrasound waves are sound waves with frequencies higher than the human audible frequencies and application of these waves in biomedical science is explored in this article. A novel approach that involved the use of ultrasound was discovered in around 1950 and since then, it is experimented on to obtain various applications like gene/drug delivery, diagnosis, theranostics, tissue engineering, etc. Ultrasound waves are sound waves travelling at frequencies above human audible frequencies and are further classified into three types: high frequency, medium frequency and low frequency, each showing different therapeutic applications. Ultrasound has shown its application in various fields like dentistry, wastewater management, etc. Apart from therapeutic use, ultrasound is also implemented in synthesis, extraction, tissue engineering, gene delivery and many more applications. This article mentions the recent applications of ultrasound as a non-invasive route for the treatment of several diseases also due to its enhanced penetration of cells which helped greatly in the delivery of drugs/genes, in the extraction of various essential biological components from plants, in the synthesis of several compounds, in the field of theranostics – a combination of diagnosis and therapy, in tissue engineering, etc.

The present study aimed to develop miconazole nitrate solid lipid nanoparticle (SLN) loaded polymeric microneedle (MN) patches (SPs) via the vacuum micromolding approach. The SLNs were fabricated through melt emulsification of stearic acid using Tween 80. SPs were prepared using chitosan, gelatin (as base materials) and polyethylene glycol 400 (as a plasticizer). The prepared formulations were evaluated for various physicochemical parameters, including particle size, polydispersity index, encapsulation efficiency, loading capacity (in the case of SLNs), folding endurance, % swelling and insertion ability (in the case of SPs). Scanning electron microscopy and differential scanning calorimetry (DSC) studies were carried out for morphological and thermal analysis, respectively. Phase analysis was carried out via X-ray diffraction (XRD). In vitro tensile strength, drug release, anti-biofilm activity and in vivo anti-biofilm activity were studied to assess the efficiency of the SLN loaded polymeric formulation. Miconazole nitrate containing SLNs appeared as smooth-surfaced aggregates and displayed a particle diameter of ∼224 nm, polydispersity index of ∼0.32, encapsulation efficiency of ∼88.88% and loading capacity of ∼8.88%. SPs exhibited evenly aligned, uniform-surfaced, sharp-tipped projections, with an acceptable folding endurance of ∼300 and % swelling of ∼359%. DSC and XRD results confirmed the incorporation of the drug within the solidified lipid matrix as an amorphous solid. The miconazole nitrate lipidic nanoparticle containing polymeric formulation exhibited a tensile strength ∼1.35 times lower than the pure drug loaded counterpart. During in vitro studies, SPs released ∼94% miconazole nitrate within 150 minutes and reduced the mass of the Candida albicans (C. albicans) biofilm by ∼79%. After 10 days of treatment with SPs, C. albicans infected wounds were healed, confirming that the prepared formulations can be used for the management of fungal biofilms.

Epigallocatechin-3-gallate (EGCG) is a key bio-active component of green tea and has demonstrated significant antidepressant activity in laboratory animals. Nano-particulate drug delivery offers great potential to overcome drawbacks associated with EGCG i.e. its low solubility and stability by transforming it into effective deliverable drugs. In the current study, nano-formulations of EGCG alone and with piperine were synthesized using antisolvent precipitation methodology followed by evaluation of their in vivo antidepressant effect in unstressed and stressed Swiss male albino mice. The mice were exposed to distinct stressors i.e. tail pinch, induction of immobilization, etc. throughout a span of three weeks. Zein, a protein nanocarrier, was nano-encapsulated with EGCG (25 mg) and EGCG + piperine (25 mg + 5 mg). For a continuous three weeks, the mice were administered EGCG-loaded nanosuspensions (25 mg kg⁻¹) and EGCG–piperine nanocomplexes (25 mg kg⁻¹). To determine the impact of various medication treatments on stressed and unstressed mice, the tail suspension test (TST) was employed as a behavioural paradigm. Mice exposed to various drug treatments were also evaluated for the effect on locomotor activity. The animals were euthanized followed by further estimation of plasma corticosterone, plasma nitrite, brain malondialdehyde, brain MAO-A, brain reduced glutathione, and brain catalase levels. The EGCG–piperine nanocomplex (25 mg kg⁻¹) and paroxetine HCl (10 mg kg⁻¹) per se significantly reduced immobility time in unstressed and stressed mice as compared to their respective control groups treated with a vehicle. However, in the case of locomotor activity, no significant effect was observed. EGCG loaded nanosuspension, EGCG–piperine nanocomplex and paroxetine HCl significantly decreased plasma nitrite, and brain MAO-A, brain malondialdehyde and brain catalase levels. However, these drug treatments significantly increased plasma corticosterone and brain reduced glutathione levels in unstressed and stressed mice as compared to their respective control groups treated with a vehicle. So, the intraperitoneal administration of nanoformulations synthesized using EGCG alone and along with piperine significantly improves the antidepressant-like behavior in mice.