Long-Acting Heterodimeric Paclitaxel-Idebenone Prodrug-Based Nanomedicine Promotes Functional Recovery after Spinal Cord Injury.

After spinal cord injury (SCI), successive systemic administration of microtubule-stabilizing agents has been shown to promote axon regeneration. However, this approach is limited by poor drug bioavailability, especially given the rapid restoration of the blood-spinal cord barrier. There is a pressing need for long-acting formulations of microtubule-stabilizing agents in treating SCI. Here, we conjugated the antioxidant idebenone with microtubule-stabilizing paclitaxel to create a heterodimeric paclitaxel-idebenone prodrug via an acid-activatable, self-immolative ketal linker and then fabricated it into chondroitin sulfate proteoglycan-binding nanomedicine, enabling drug retention within the spinal cord for at least 2 weeks and notable enhancement in hindlimb motor function and axon regeneration after a single intraspinal administration. Additional investigations uncovered that idebenone can suppress the activation of microglia and neuronal ferroptosis, thereby amplifying the therapeutic effect of paclitaxel. This prodrug-based nanomedicine simultaneously accomplishes neuroprotection and axon regeneration, offering a promising therapeutic strategy for SCI.

Excipients for Novel Inhaled Dosage Forms: An Overview.

Pulmonary drug delivery is a form of local targeting to the lungs in patients with respiratory disorders like cystic fibrosis, pulmonary arterial hypertension (PAH), asthma, chronic pulmonary infections, and lung cancer. In addition, noninvasive pulmonary delivery also presents an attractive alternative to systemically administered therapeutics, not only for localized respiratory disorders but also for systemic absorption. Pulmonary delivery offers the advantages of a relatively low dose, low incidence of systemic side effects, and rapid onset of action for some drugs compared to other systemic administration routes. While promising, inhaled delivery of therapeutics is often complex owing to factors encompassing mechanical barriers, chemical barriers, selection of inhalation device, and limited choice of dosage form excipients. There are very few excipients that are approved by the FDA for use in developing inhaled drug products. Depending upon the dosage form, and inhalation devices such as pMDIs, DPIs, and nebulizers, different excipients can be used to provide physical and chemical stability and to deliver the dose efficiently to the lungs. This review article focuses on discussing a variety of excipients that have been used in novel inhaled dosage forms as well as inhalation devices.

Detrimental Impacts of Pharmaceutical Excipient PEG400 on Gut Microbiota and Metabolome in Healthy Mice.

Polyethylene glycol 400 (PEG400) is a widely used pharmaceutical excipient in the field of medicine. It not only enhances the dispersion stability of the main drug but also facilitates the absorption of multiple drugs. Our previous study found that the long-term application of PEG400 as an adjuvant in traditional Chinese medicine preparations resulted in wasting and weight loss in animals, which aroused our concern. In this study, 16S rRNA high-throughput sequencing technology was used to analyze the diversity of gut microbiota, and LC-MS/MS Q-Exactive Orbtriap metabolomics technology was used to analyze the effect of PEG400 on the metabolome of healthy mice, combined with intestinal pathological analysis, aiming to investigate the effects of PEG400 on healthy mice. These results showed that PEG400 significantly altered the structure of gut microbiota, reduced the richness and diversity of intestinal flora, greatly increased the abundance of Akkermansia muciniphila (A. muciniphila), increased the proportion of Bacteroidetes to Firmicutes, and reduced the abundance of many beneficial bacteria. Moreover, PEG400 changed the characteristics of fecal metabolome in mice and induced disorders in lipid and energy metabolism, thus leading to diarrhea, weight loss, and intestinal inflammation in mice. Collectively, these findings provide new evidence for the potential effect of PEG400 ingestion on a healthy host.

Polyenylphosphatidylcholine as bioactive excipient in tablets for the treatment of liver fibrosis.

Liver fibrosis is a condition characterized by the accumulation of extracellular matrix (ECM) arising from the myofibroblastic transdifferentiation of hepatic stellate cells (HSCs) occurring as the natural response to liver damage. To date, no pharmacological treatments have been specifically approved for liver fibrosis. We recently reported a beneficial effect of polyenylphosphatidylcholines (PPCs)-rich formulations in reverting fibrogenic features of HSCs. However, unsaturated phospholipids' properties pose a constant challenge to the development of tablets as preferred patient-centric dosage form. Profiting from the advantageous physical properties of the PPCs-rich Soluthin® S 80 M, we developed a tablet formulation incorporating 70% w/w of this bioactive lipid. Tablets were characterized via X-ray powder diffraction, thermogravimetry, and Raman confocal imaging, and passed the major compendial requirements. To mimic physiological absorption after oral intake, phospholipids extracted from tablets were reconstituted as protein-free chylomicron (PFC)-like emulsions and tested on the fibrogenic human HSC line LX-2 and on primary cirrhotic rat hepatic stellate cells (PRHSC). Lipids extracted from tablets and reconstituted in buffer or as PFC-like emulsions exerted the same antifibrotic effect on both activated LX-2 and PRHSCs as observed with plain S 80 M liposomes, showing that the manufacturing process did not interfere with the bioactivity of PPCs.

Review of Applications of Cyclodextrins as Taste-Masking Excipients for Pharmaceutical Purposes.

It is widely recognized that many active pharmaceutical ingredients (APIs) have a disagreeable taste that affects patient acceptability, particularly in children. Consequently, developing dosage forms with a masked taste has attracted a lot of interest. The application of cyclodextrins as pharmaceutical excipients is highly appreciated and well established, including their roles as drug delivery systems, solubilizers and absorption promoters, agents that improve drug stability, or even APIs. The first work describing the application of the taste-masking properties of CDs as pharmaceutical excipients was published in 2001. Since then, numerous studies have shown that these cyclic oligosaccharides can be effectively used for such purposes. Therefore, the aim of this review is to provide insight into studies in this area. To achieve this aim, a systematic evaluation was conducted, which resulted in the selection of 67 works representing both successful and unsuccessful works describing the application of CDs as taste-masking excipients. Particular attention has been given to the methods of evaluation of the taste-masking properties and the factors affecting the outcomes, such as the choice of the proper cyclodextrin or guest-host molar ratio. The conclusions of this review reveal that the application of CDs is not straightforward; nevertheless, this solution can be an effective, safe, and inexpensive method of taste masking for pharmaceutical purposes.

Topical delivery systems containing clotrimazole for the management of candidiasis: Effect of different excipients and enhanced antifungal activity of nanovesicles.

WHO classified Candida albicans as one of the four critical priority fungi for public health worldwide in 2022. Conventional topical formulations commercially available for the treatment of cutaneous candidiasis are associated with low drug bioavailability at the infection site and the lack of a sustained therapeutic effect. The main objectives of this work were to develop new topical administration systems of clotrimazole (CLT) and study the influence of surfactants on the antifungal inhibitory efficacy. Therefore, the minimum concentration of CLT required to inhibit 50 % of growth (MIC50) was determined, obtaining a value of approximately 15 ng/mL. A non-ionic emulsion type 1, Beeler base cream, hydrogel and liposomes containing CLT were designed, prepared, characterized and their antifungal activity against C. albicans was tested. CLT loaded liposomes were small in size (102 nm), homogeneous (polydispersity index = 0.3) and uncharged (+0.07 mV), showing higher antifungal activity against C. albicans than that of the commercially available cream Canesten®. Furthermore, the antifungal activity of CLT was reduced in combination with surfactants such as Tween-80/Span-80 or Brij-S10. Sodium lauryl sulphate showed a fungicidal effect that disappeared when formulated as part of the Beeler base cream.

Cell membrane-based biomimetic vehicles for effective central nervous system target delivery: Insights and challenges.

Central nervous system (CNS) disorders, including brain tumor, ischemic stroke, Alzheimer's disease, and Parkinson's disease, threaten human health. And the existence of the blood-brain barrier (BBB) hinders the delivery of drugs and the design of drug targeting delivery vehicles. Over the past decades, great interest has been given to cell membrane-based biomimetic vehicles since the rise of targeting drug delivery systems and biomimetic nanotechnology. Cell membranes are regarded as natural multifunction biomaterials, and provide potential for targeting delivery design and modification. Cell membrane-based biomimetic vehicles appear timely with the participation of cell membranes and nanoparticles, and raises new lights for BBB recognition and transport, and effective therapy with its biological multifunction and high biocompatibility. This review summarizes existing challenges in CNS target delivery and recent advances of different kinds of cell membrane-based biomimetic vehicles for effective CNS target delivery, and deliberates the BBB targeting mechanism. It also discusses the challenges and possibility of clinical translation, and presents new insights for development.

Recent trends and updates on ultradeformable and elastic vesicles in ocular drug delivery.

Ocular drug delivery is enigmatic on account of various physiological precorneal barriers that ultimately hinder efficient drug penetration and corneal absorption. Ultradeformable vesicles embody non-ionic surfactants, edge activators and vesicular builders that provide enormous elasticity and deformability. The elastic vesicles can cross the ocular barriers owing to their peculiar squeezability and distorting ability and, thus, establish an infallible shot for ocular delivery. This review provides an overview of the recent advancements and updates of elastic vesicles as effective ocular drug delivery vehicles.

Novel food drug interaction mechanism involving acyclovir, chitosan and endogenous mucus.

Drug absorption from drug products may be affected by pharmaceutical excipients and/or food additives through different mechanisms. Chitosan is a recognized nutraceutical, with potential as an excipient due to its permeability enhancer properties. While chitosan properties have been evaluated in in vitro and pre-clinical models, studies in humans are scarce. Unexpectedly, a controlled clinical trial showed chitosan actually reduced acyclovir bioavailability. The effect seems to be related to an interaction with gastrointestinal mucus that prevents further absorption, although more in depth research is needed to unravel the mechanism. In this paper, we propose a mechanism underlying this excipient effect. The mucus - chitosan interaction was characterized and its effect on acyclovir diffusion, permeation and bioaccessibility was investigated. Further, pharmacokinetic modeling was used to assess the clinical relevance of our findings. Results suggest that in situ coacervation between endogenous mucus and chitosan rapidly entrap 20-30% of acyclovir dissolved dose in the intestinal lumen. This local reduction of acyclovir concentration together with its short absorption window in the small intestine would explain the reduction in acyclovir Cmax and AUC. This study highlights the importance of considering mucus in any biorelevant absorption model attempting to anticipate the effect of chitosan on drug absorption.

Skin permeation of curcumin nanocrystals: Effect of particle size, delivery vehicles, and permeation enhancer.

Nanocrystals are characterized by high drug loading, low carrier toxicity, and great structural stability. Therefore, they are a promising and versatile strategy for enhancing the local delivery of insoluble drugs. They achieve this by improving skin adhesion, concentration gradients, and hair follicle accumulation, as well as generating corona diffusion (which forms through the overlap of dissolved drug molecules around a nanocrystal). The development of suitable formulations for enhancing the passive diffusion and/or follicular targeting of nanocrystals is of great importance to clinical practice. We sought to elucidate the influence of particle size, a penetration enhancer, and delivery vehicles on the follicular accumulation and passive dermal permeation of nanocrystals. For this purpose, curcumin nanocrystals (particle size: 60, 120, and 480 nm) were incorporated into xanthan gum gels (delivery vehicles) with propylene glycol (penetration enhancer). This evaluation was performed in a porcine skin model. The results showed that xanthan gum reduced the follicular penetration and passive skin accumulation of curcumin nanocrystals. The propylene glycol enhanced the skin penetration and retention of curcumin nanocrystals in vitro for 24 h. The curcumin nanocrystals of smaller particle size (i.e., 60 and 120 nm) displayed higher passive skin penetration versus those with larger particle size (i.e., 480 nm); however, the latter type showed deeper follicular accumulation. In conclusion, the delivery vehicles, penetration enhancer, and particle sizes examined in this study affect the dermal penetration and accumulation of curcumin nanocrystals. Hence, their effects should be adequately considered when designing formulations of such nanocrystals.

Study on the preparation of EGCG-γ-Cyclodextrin inclusion complex and its drug-excipient combined therapeutic effects on the treatment of DSS-induced acute ulcerative colitis in mice.

In this study, γ-cyclodextrins (γ-CD) and epigallocatechin-3-gallate (EGCG) were designed to form an inclusion complex (EGCG-γ-IC) for ulcerative colitis (UC) treatment. The drug-excipient combined therapeutic potential of γ-CD and EGCG was verified, when stability and compliance were also achieved. EGCG-γ-IC effectively inhibited the secretions of NO, TNF-α, and IL-6 and the intracellular ROS in RAW264.7 cells. The effectiveness of EGCG-γ-IC in treating DSS-induced acute UC in mice was observed including improving the histological conditions of the colon, reducing the levels of IL-1ß, IL-6, and TNF-α in serum, and restoring MPO, GSH, and sIgA levels in intestinal tissues. Moreover, EGCG-γ-IC had a more prominent effect on regulating bacterial dysbiosis caused by DSS than EGCG and γ-CD alone. Therefore, EGCG-γ-IC designed here displayed UC treating capacity with safety in the long-term application and promised an industrial production potential due to its excellent storage stability.

The Assessment of Skin Homeostasis Changes after Using Different Types of Excipients in Healthy Individuals.

Excipients are used as vehicles for topical treatments; however, there are not many studies that evaluate the impact of different excipients themselves. The aim of this research is to assess skin homeostasis changes in healthy individuals after using water/oil (W/O), oil/water (O/W), Beeler base, foam and Vaseline excipients. A within-person randomized trial was conducted that included healthy individuals without previous skin diseases. Skin barrier function parameters, including stratum corneum hydration (SCH), transepidermal water loss (TEWL), pH, temperature, erythema, melanin and elasticity (R0, R2, R5 and R7), were measured on the volar forearm before and after using each excipient. Sixty participants were included in the study, with a mean age of 32 years. After applying w/o excipient erythema decreased by 25 AU, (p < 0.001) and elasticity increased by 6%. After using the o/w excipient, erythema decreased by 39.36 AU (p < 0.001) and SCH increased by 6.85 AU (p = 0.009). When applying the Beeler excipient, erythema decreased by 41.23 AU (p < 0.001) and SCH increased by 15.92 AU (p < 0.001). Foam and Vaseline decreased TEWL and erythema. Excipients have a different impact on skin barrier function. Knowing the effect of excipients on the skin could help to develop new topical treatments and help specialists to choose the best excipient according to the pathology.

The effect of surfactant type on characteristics, skin penetration and anti-aging effectiveness of transfersomes containing amniotic mesenchymal stem cells metabolite products in UV-aging induced mice.

Transfersome has been developed to enhance dermal delivery of amniotic mesenchymal stem cell metabolite products (AMSC-MP). AMSC-MP contains many growth factors for managing skin aging, thus improving the quality of an adjusted life year. This study aims to determine the effect of surfactant types acting as the edge activator on transfersome-loading AMSC-MP. Transfersome was prepared by thin-layer hydration method and composed of l-α-phosphatidylcholine as a phospholipid and three types of surfactants, namely; cationic (stearylamine), anionic (sodium cholate), and nonionic surfactant (Tween 80) at a weight ratio of 85:15, respectively. Transfersomes were evaluated for physical characteristics, penetration, effectiveness, and safety. The results showed that sodium cholate, an anionic surfactant, produced the smallest transfersome particle size, i.e., 144.2 ± 3.2 nm, among all formulas. Trans-SA containing stearylamine had a positive charge of 41.53 ± 6.03 mV compared to Trans-SC and Trans-TW, whose respective charges were -56.9 ± 0.55 mV and -41.73 ± 0.86 mV. The small particle size and low negative value of zeta potential enabled high dermal penetration by transfersomes containing AMSC-MP, while the positive charge of stearylamine hindered its penetration of deeper skin layers. Trans-SC and Trans-TW produced higher collagen density values at 77.11 ± of 4.15% and 70.05 ± of 6.95%, than that of Trans-SA. All the AMSC-MP transfersomes were relatively safe with 0.5-1.0 macrophage cell numbers invaded the dermis per field of view. In conclusion, sodium cholate, an anionic surfactant, demonstrated considerable capacity as the edge activator of transfersome-loading AMSC-MP for skin anti-aging therapy.

Sex-specific effects of excipients on oral drug bioavailability.

The mechanism of action of excipients eliciting sex differences in drug bioavailability is poorly understood. In this study, the excipients Cremophor RH 40 (PEG 40 hydrogenated castor oil), Poloxamer 188 (2-methyloxirane) and Tween 80 (polyoxyethylene (80) sorbitan monooleate) were screened at 0.07 - 5% concentrations for their effect on ranitidine bioavailability in male and female Wistar rats. We show that all excipient concentrations significantly increased ranitidine bioavailability in male, but not female, rats. The effect of these excipients on the intestinal efflux transporters P-glycoprotein (P-gp), breast cancer resistant protein (BCRP) and multi-drug resistant protein 2 (MRP2) were also monitored. Measured by ELISA assay, in male rats, peak reductions in intestinal P-gp protein expression occurred in the presence of 1% Cremophor RH 40 and Poloxamer 188 and 0.5% Tween 80. In contrast, no distinct changes were observed in female intestinal P-gp expression. Unlike P-gp, all excipients had a positive effect on MRP2 protein expression - albeit only in males - in a concentration-dependent manner. The excipients did not modulate intestinal BCRP protein expression in either sex. Endogenous hormones and a nuclear receptor (testosterone, oestradiol and pregnane X receptor; PXR) that are purported to regulate intestinal efflux membrane transporter expression were also quantified. In the presence of all excipients, testosterone levels significantly elevated in males, although PXR levels reduced at similar rates in both sexes. No significant effects were identified in oestradiol levels in male and female rats. It is clear that excipients are not inert and their pathway for modulating drug response is multi-dimensional and specific between sexes. This study showed that excipients increased drug bioavailability of a P-gp drug substrate due to its reductive effect on intestinal P-gp expression; we propose that this link may be due to the excipients modulating fundamental testosterone levels. Understanding the implication of excipients on intestinal physiology and hormone levels can therefore improve pharmaceutical design, clinical efficacy and instigate next generation personalised, sex-specific formulations.

Physical and barrier changes in gastrointestinal mucus induced by the permeation enhancer sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC).

Drug delivery systems (DDS) for oral delivery of peptide drugs contain excipients that facilitate and enhance absorption. However, little knowledge exists on how DDS excipients such as permeation enhancers interact with the gastrointestinal mucus barrier. This study aimed to investigate interactions of the permeation enhancer sodium 8-[(2-hydroxybenzoyl)amino]octanoate (SNAC) with ex vivo porcine intestinal mucus (PIM), ex vivo porcine gastric mucus (PGM), as well as with in vitro biosimilar mucus (BM) by profiling their physical and barrier properties upon exposure to SNAC. Bulk mucus permeability studies using the peptides cyclosporine A and vancomycin, ovalbumin as a model protein, as well as fluorescein-isothiocyanate dextrans (FDs) of different molecular weights and different surface charges were conducted in parallel to mucus retention force studies using a texture analyzer, rheological studies, cryo-scanning electron microscopy (cryo-SEM), and single particle tracking of fluorescence-labelled nanoparticles to investigate the effects of the SNAC-mucus interaction. The exposure of SNAC to PIM increased the mucus retention force, storage modulus, viscosity, increased nanoparticle confinement within PIM as well as decreased the permeation of cyclosporine A and ovalbumin through PIM. Surprisingly, the viscosity of PGM and the permeation of cyclosporine A and ovalbumin through PGM was unaffected by the presence of SNAC, thus the effect of SNAC depended on the regional site that mucus was collected from. In the absence of SNAC, the permeation of different molecular weight and differently charged FDs through PIM was comparable to that through BM. However, while bulk permeation of neither of the FDs through PIM was affected by SNAC, the presence of SNAC decreased the permeation of FD4 and increased the permeation of FD150 kDa through BM. Additionally, and in contrast to observations in PIM, nanoparticle confinement within BM remained unaffected by the presence of SNAC. In conclusion, the present study showed that SNAC altered the physical and barrier properties of PIM, but not of PGM. The effects of SNAC in PIM were not observed in the BM in vitro model. Altogether, the study highlights the need for further understanding how permeation enhancers influence the mucus barrier and illustrates that the selected mucus model for such studies should be chosen with care.

Bacterial nanocellulose patches as a carrier for hydrating formulations to improve the topical treatment of nail diseases.

Bacterial nanocellulose has been widely investigated for wound healing applications, mainly due to its moisturizing capabilities and biocompatibility. Even though the topical therapy of nail diseases could benefit from these properties, this application has not yet been investigated. Therefore, actively hydrating nail patches based on bacterial nanocellulose were developed to improve the delivery of ciclopirox olamine and Boswellia serrata extract through the nail plate. The nanocellulose matrix was used to enable the application of hydration enhancing solutions based on glycerol and urea as a mechanically stable patch. While the favorable mechanical characteristics of the material remained unchanged, an increase of the incorporated glycerol concentration enhanced the transparency and wetting capacity of the patches. A biphasic drug release from the patches could be observed for drug and extract with a faster release for the hydrophilic ciclopirox olamine. High glycerol concentrations correlated with increased cumulative release and permeation through keratin films for drug and extract, demonstrating the hydration driven permeation enhancement. Patches containing ciclopirox olamine showed strong antimycotic effects against relevant pathogens for onychomycosis. The present finding proposed the combination of bacterial nanocellulose with glycerol, urea and different drug as a promising platform for the local treatment of nail diseases.

3D printing hybrid materials using fused deposition modelling for solid oral dosage forms.

3D printing in the pharmaceutical and healthcare settings is expanding rapidly, such as the rapid prototyping of orthotics, dental retainers, drug-loaded implants, and pharmaceutical solid oral dosage forms. Through 3D printing, we have the capability to precisely control dose, release kinetics, and several aesthetic features of dosage forms such as colour, shape, and texture. Additionally, polypills can be created with combinations of medications in one solid dosage form at completely customisable strengths that would be extremely difficult to obtain commercially. As the technology and formulations developed through 3D printing are expanding, the development of new hybrid materials to obtain superior formulations are also gaining momentum. In this review we collate data on the importance of developing hybrid formulations of polymers, drugs and excipients necessary to produce reliable and high-quality 3D printed dosage forms with a special emphasis on fused deposition modelling (FDM). FDM technology is one of the most widely used forms of 3D printing and has demonstrated compatibility with unique polymer-based hybrids to allow for enhanced drug delivery, protection of thermolabile drugs, modifiable release kinetics, and more. The data collated covers different categories of hybrids as well as the methods used to fabricate them, and their respective effects on the properties of 3D printed solid oral dosage forms. Therefore, this review will provide an overview of upcoming and emerging trends in pharmaceutical 3D printing formulation compositions.

Anti-Fatigue Effects of Lycium barbarum Polysaccharide and Effervescent Tablets by Regulating Oxidative Stress and Energy Metabolism in Rats.

The purpose of this study was to investigate the anti-fatigue effect of natural Lycium barbarum polysaccharide (LBP) during exercise, develop a functional anti-fatigue effervescent tablet by applying LBP to practical products, and help patients who have difficulty swallowing conventional tablets or capsules. LBP was extracted with water, and DEAE-52 cellulose was used for purification. The chemical structure and monosaccharide composition of LBP by Fourier transform infrared spectroscopy (FI-IR) and ion chromatography (IC). Lycium barbarum polysaccharide effervescent tablets (LBPT) were prepared by mixing LBP and an excipient. Animal experiments showed that LBP and LBPT significantly increased the exhaustive swimming time in rats. LBP and LBPT improved biochemical markers in rat serum, such as lactic acid and creatine kinase, enhanced the antioxidant capacity of rat muscle, and reversed the decrease in serum glucose, ATP and glycogen content caused by exercise. Transmission electron microscopy showed that LBP and LBPT increased the density of mitochondria in rat liver. In addition, molecular experiments showed that LBP and LBPT could improve oxidative stress caused by exercise by regulating the Nrf2/HO-1 signaling pathway and regulating energy metabolism via the AMPK/PGC-1α signaling pathway.

Effect and Mechanism of Pharmaceutical Excipients on Berberine to Alleviate Ulcerative Colitis via Regulating Gut Microbiota.

BACKGROUND: Various potential effect of drugs on alleviating diseases by regulating intestinal microbiome as well as the pharmaceutical excipients on gut microbiota has been revealed. However, the interaction between them is rarely investigated. METHODS: Histological analysis, immunohistochemistry analysis, enzyme-linked immunosorbent assay (ELISA) analysis, RT-qPCR, and 16S rRNA analysis were utilized to explore the effect mechanism of the five excipients including hydroxypropyl methylcellulose (HPMC) F4M, Eudragit (EU) S100, chitosan (CT), pectin (PT), and rheum officinale polysaccharide (DHP) on berberine (BBR) to cure UC. RESULTS: The combined BBR with PT and DHP group exhibited better therapeutic efficacy of UC with significantly increased colon length, and decreased hematoxylin-eosin (H&E) scores than other groups. Furthermore, the expression of tight junction ZO-1 and occludin in colon tissue were upregulated, and claudin-2 was downregulated. Ultimately, the serum content of tumor necrosis (TNF)-α, interleukin (IL)-1ß, and IL-6 was decreased. Moreover, the combined BBR with PT significantly promoted the restoration of gut microbiota. The relative abundance of Firmicutes and Lactobacillus was significantly increased by the supplement of PT and DHP, and the relative abundance of Proteobacteria was downregulated. CONCLUSIONS: Our study may provide a new perspective that the selection of pharmaceutical excipients could be a crucial factor affecting the drugs' therapeutic efficiency outcome.