Current Drug Delivery - Volume 22, Issue 5, 2025

Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is one of the leading causes of death and an immense financial burden on healthcare systems. Rifaximin (RFX) has good antibacterial activity against MRSA, but its clinical application is limited due to its poor oral absorption.

In order to improve the oral bioavailability of rifaximin and expand the clinical application of RFX for MRSA pneumonia, this study developed a RFX-loaded myristic acid solid lipid nanoparticles (RFX-SLNs).

This study first screened the formula of RFX-SLNs through single factor screening. After that, the particle size, zeta potential and polydispersity index (PDI) of the RFX-SLNs were measured, the morphology of RFX-SLNs was observed by transmission electron microscopy, and the encapsulation efficiency (EE) and drug loading capacity (LC) of RFX-SLNs were detected by high performance liquid chromatography. Then, the sustained release ability and oral bioavailability of RFX-SLNs were studied through in vitro release and pharmacokinetics. Finally, the therapeutic effect of RFX-SLNs on MRSA pneumonia infection was studied by using a mouse MRSA pneumonia infection model.

The optimal formulation of RFX-SLNs was 1% RFX with a water (3% PVA) and oil (myristic acid) ratio of 1:19. RFX-SLNs were spherical shape with a smooth surface and uniform size. The EE and LC of three different batches of RFX-SLNs were 89.35±2.47%, 90.45±3.69%, 88.72±1.18%, and 9.50 ± 0.01%, 10.09±0.01%, and 9.68±0.00%, respectively. In vitro release and pharmacokinetic studies showed that the myristic acid solid lipid nanoparticles showed excellent sustained release as expected and increased the oral bioavailability of RFX by 2.18 times. RFX-SLNs showed a good therapeutic effects in a mouse MRSA pneumonia infection model.

This study indicates that the myristic acid solid lipid nanoparticles might be an effective way to enhance the oral absorption and therapy effects of RFX and other insoluble drugs.

Zeolitic imidazolate frameworks (ZIFs) play a crucial role among metal-organic frameworks due to their highly desirable properties, including high surface area, appropriate pore size, and excellent thermal and chemical stability.

In this study, ZIF-8 loaded with aspirin and coated using pectin (ZIF-8/Asp@Pectin) was utilized as a suitable and effective platform for the drug delivery system. The preparation of this coated MOF followed environmentally friendly methods, and aspirin was successfully loaded.

Characterization of the obtained ZIF-8/Asp@Pectin was performed using X-ray diffraction (XRD), scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), Fourier Transform Infrared (FT-IR) spectroscopy, and BET analysis.

The release of aspirin from ZIF-8/Asp@Pectin was studied using UV–Vis spectroscopy at 258 nm under in vitro conditions in HCl and PBS buffer solutions.

Traditional Chinese medicine formulations often contain hydrophobic components with limited solubility and stability, leading to low oral bioavailability. Self-assembled nanoparticles (SANs) have shown promise in enhancing oral bioavailability of these components. However, whether un-decocted Chinese herbal pellets can generate SANs and the impact of SANs formed by multiple components on pharmacokinetic parameters remains unexplored.

In this study, single-factor approach was employed to determine the optimal separation method of nano-emulsion phase of XiaoYao pill (N-XY). Morphological and particle size analyses confirmed the nanoscale nature of N-XY. High-performance liquid chromatography (HPLC) fingerprint analysis was conducted to compare the distribution of active ingredients among three different phases of XiaoYao pill (XY pill). In vitro release studies were performed to evaluate the release mechanism of four ingredients from N-XY. Additionally, in vivo pharmacokinetics and tissue distribution behaviors were investigated in rats.

N-XY exhibited uniform and stable characteristics as a water-in-oil (O/W) nano-emulsion. Fingerprint analysis identified 25 characteristic peaks and 8 key ingredients in N-XY, with the highest peak areas. In vitro release studies showed a sustained release behavior of N-XY. The pharmacokinetics study showed that the ferulic acid of N-XY had a 1.37-fold higher AUC, 1.44-fold lower Vd/F, 1.39-fold lower CL/F, and a prolonged t1/2 than A-XY, indicating enhanced bioavailability due to reduced elimination. Furthermore, the tissue distribution revealed that the levels of paeoniflorin and ferulic acid from N-XY significantly increased in liver, spleen, lungs, uterus and ovaries, exhibiting targeting characteristics.

This study comprehensively explored the formation, characterization, and pharmacokinetics of nano-emulsion in XY pill, introducing novel perspectives and initiating preliminary research on potential SANs in un-decocted traditional Chinese medicine formulations. It also emphasized the importance of enhancing pharmacokinetics of hydrophobic components in Chinese herbal formulations and laid the foundation for future nano-formulation research for XY pill.

Although lignin is one of the most naturally abundant biopolymers, the overall status of its utilization has long been subpar. The ability of Lignin to readily self-assemble into nanoparticles, along with its good biocompatibility and minimal toxicity, makes it a perfect agent for nanocarriers and drug delivery.

Hence, in this study, we have attempted to examine lignin nanoparticles (LNPs) as an efficient pH-responsive nanocarrier for gastric-irritant oral NSAID, aspirin. Alkali lignin (AL) was extracted from rice straw via alkaline treatment, and the lignin nanoparticles were synthesized from lignin using the acid precipitation method. The average particle size was 201.37 ± 1.20 nm, and the synthesized LNPs exhibited a spherical shape and smooth outer surface along with high polydispersity (PDI= 0.284 ± 0.012). The LNPs showed moderate hemocompatibility during in vitro hemolysis studies. The nanoparticles presented nearly similar chemical structures to the AL from which they were developed, and the FT-IR absorption spectra confirmed the similarity of this chemical structure to the LNPs and AL. Aspirin was successfully loaded into the LNPs with a satisfactory drug loading value of 39.12 ± 1.50 and an excellent encapsulation efficiency value of 91.44 ± 0.59.

Finally, the LNPs were capable of protecting the loaded drug at the acidic pH of the stomach (1.2) with just 29.20% release of the loaded aspirin after 10 h of observation in vitro. Contrarily, the LNPs were capable of rapidly releasing the aspirin at the basic pH of the intestine (7.4) with nearly 90% release of the loaded drug after 10 h observation in vitro. The basic pH of the intestine might lead to gradual dissociation of the LNPs followed by swift release of the loaded cargo.

These findings substantiate that the LNPs carry the potential to be an apt and safe nanocarrier for oral drugs like aspirin as well as parenteral drugs, and LNPs can be utilized as an efficient alternative to enteric coating.

Psoriasis is a chronic inflammatory skin disorder that poses significant challenges regarding effective and targeted drug delivery. Bioactive substances like betulin have shown tremendous utility in treating these conditions; however, they pose limited utility owing to their physicochemical characteristics. Here, we aimed to develop a novel topical dosage form for treating psoriasis, utilising betulin-loaded Nanostructured lipid carriers (NLCs) incorporated into a hydrogel matrix.

The optimization of the formulation was meticulously conducted using a design expert-13 software, and its diverse physicochemical attributes were thoroughly examined. Evaluating betulin's in vitro release pattern from the NLC-hydrogel demonstrated consistent and regulated drug release properties. Additionally, the formulation demonstrated improved skin penetration abilities as determined by in vitro skin permeation experiments employing Franz diffusion cells—furthermore, the therapeutic effectiveness of the betulin-NLC-hydrogel was assessed by an in vivo experiment carried out using an imiquimod-induced psoriasis-like skin inflammation model in BALB/c female mice.

The NLCs exhibited a pH of 5.67±0.86, particle size of 148.16±12.66 nm, and zeta potential of -22.84±2.37 mV, ensuring stability and suitability for topical use. The gel, with a pH of 6.05±0.43 and viscosity of 17550±120 cPs, showed enhanced skin hydration and lipid restoration. Drug release studies indicated a slower release from NLCs and gel, improving skin retention. Stability tests revealed that the formulations were stable at room temperature but not at elevated temperatures. The in vitro safety profile of the formulation revealed no significant adverse effects on HaCaT cell lines. The NLC gel demonstrated significant anti-psoriatic activity, reducing inflammation and cytokine levels.

The betulin-NLC-hydrogel formulation exhibited promising characteristics for the topical treatment of psoriasis, showcasing optimised drug delivery, sustained release, and notable therapeutic efficacy. The findings from this study provide a foundation for the potential clinical translation of this innovative topical dosage form for improved psoriasis management.

Tetrandrine (TET) has multiple pharmacological activities, but its water solubility is poor, which is the main reason for its low bioavailability.

The purpose of this study was to prepare TET nanocrystals (TET-NCs) using a grinding method to enhance the dissolution rate and ultimately improve the bioavailability of TET.

TET-NCs were synthesized via media milling, employing Poloxam 407 (P407) as surface stabilizer and mannitol as a cryoprotectant during freeze-drying. The crystal structure, particle diameter, and zeta potential were characterized using differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The in vitro release behavior and pharmacokinetics of TET-NCs were assessed. The cytotoxicity of TET and TET-NCS on RAW264.7 cells was determined by the CCK-8 method.

The particle size of TET-NCs was 360.0±7.03 nm, PDI was 0.26±0.03, and zeta potential was 6.64±0.22 mV. The cumulative dissolution within 60 minutes was 96.40±2.31%. The pharmacokinetic study showed that AUC0-72 h and Cmax of TET-NCs were significantly enhanced by 3.07 and 2.57 times, respectively, compared with TET (p<0.01). TET-NCs significantly increased the cell inhibition on RAW264.7 cells compared to the TET (P<0.01).

The preparation of TET-NCs enhanced dissolution rate and bioavailability significantly, and it also improved the inhibition effect of RAW264.7 cells.