Piperine liposome-embedded in hyaluronan hydrogel as an effective platform for prevention of postoperative peritoneal adhesion.

This study aimed to prepare piperine (PIP) loaded liposomes in hyaluronic acid (HA) hydrogel to provide a hybrid superstructure for postoperative adhesion prevention. Liposomes were prepared using thin-film hydration method. The optimised formulation was characterised by size, SEM, TEM, FTIR, encapsulation efficiency (EE)% (w/w), and release pattern. Liposome-in-hydrogel formulation was investigated by rheology, SEM, and release studies. The efficacy was evaluated in a rat peritoneal abrasion model. EE% (w/w) increased with increasing lipid concentration from 10 to 30; however, a higher percentage of Chol reduced EE% (w/w). The optimised liposome (EE: 68.10 ± 1.71% (w/w), average diameter: 513 ± 8 nm, PDI: 0.15 ± 0.04) was used for hydrogel embedding. No sign of adhesion in 5/8 rats and no collagen deposition confirmed the in vivo effectiveness of the optimised formulation. Overall, providing a sustained delivery of PIP, the developed liposome-in-hydrogel formulation can be a promising carrier to prevent postoperative adhesion.

Piperine-loaded electrospun nanofibers, an implantable anticancer controlled delivery system for postsurgical breast cancer treatment.

Tumorectomy followed by radiotherapy, hormone, and chemotherapy, are the current mainstays for breast cancer treatment. However, these strategies have systemic toxicities and limited treatment outcomes. Hence, there is a crucial need for a novel controlled release delivery system for implantation following tumor resection to effectively prevent recurrence. Here, we fabricated polycaprolactone (PCL)-based electrospun nanofibers containing piperine (PIP), known for chemopreventive and anticancer activities, and also evaluated the impact of collagen (Coll) incorporation into the matrices. In addition to physicochemical characterization such as morphology, hydrophilicity, drug content, release properties, and mechanical behaviors, fabricated nanofibers were investigated in terms of cytotoxicity and involved mechanisms in MCF-7 and 4T1 breast tumor cell lines. In vivo antitumor study was performed in 4T1 tumor-bearing mice. PIP-PCL75-Coll25 nanofiber was chosen as the optimum formulation due to sustained PIP release, good mechanical performance, and superior cytotoxicity. Demonstrating no organ toxicity, animal studies confirmed the superiority of locally administered PIP-PCL75-Coll25 nanofiber in terms of inhibition of growth tumor, induction of apoptosis, and reduction of cell proliferation compared to PIP suspension, blank nanofiber, and the control. Taken together, we concluded that PIP-loaded nanofibers can be introduced as a promising treatment for implantation upon breast tumorectomy.

Curcumin polymeric membranes for postoperative peritoneal adhesion: Comparison of nanofiber vs. film and phospholipid-enriched vs. non-enriched formulations.

Intra-abdominal adhesion remains a major postoperative problem and is able to place individuals at lifelong risk of serious complications. Among available approaches, insertion of a barrier membrane at the site of injury partially inhibited adhesion formation. Moreover, the local administration of an anti-adhesive agent showed some favorable effects. In this study, we aimed to prepare and fully characterize polycaprolactone (PCL)-based film casts and electrospun nanofibers (NFs) containing a natural anti-inflammatory agent, curcumin (CUR), with extended-release properties. We also compared their efficiencies in preventing tissue adhesions. Additionally, the impact of soy phosphatidylcholine (SPC) enrichment on adhesion prevention was investigated. Prepared membranes were evaluated in terms of surface morphology (SEM, AFM), surface wettability, CUR release profiles, structural properties (FTIR, XRD, DSC), and mechanical behaviors. To further analyze the anti-adhesion effectiveness, a cecal abrasion model was performed on rats. SEM and AFM images showed a smoother surface in SPC-containing films. Concerning NFs, uniform bead-free fibers were observed and SPC containing NFs showed higher conductivity and lower viscosity and therefore, smaller fibers. All formulations exhibited sustained drug release over 4 weeks. In vivo findings revealed the superior performance of films compared to NFs and phospholipid-enriched formulations over non-enriched ones. Among all film formulations and in comparison to the positive control (Seprafilm®), CUR-SPC-PCL films significantly reduced peritoneal adhesions, as evidenced by gross examination, histological evaluation and immunohistochemical (IHC) analysis. The remarkable in vivo anti-adhesion activity together with suitable in vitro properties have made CUR-SPC-PCL films a promising system for postoperative anti-adhesion purposes in the clinic.

Nanoformulation strategies for improving intestinal permeability of drugs: A more precise look at permeability assessment methods and pharmacokinetic properties changes.

The therapeutic efficacy of orally administered drugs is often restricted by their inherent limited oral bioavailability. Low water solubility, limited permeability through the intestinal barrier, instability in harsh environment of the gastrointestinal (GI) tract and being substrate of the efflux pumps and the cytochrome P450 (CYP) can impair oral drug bioavailability resulting in erratic and variable plasma drug profile. As more drugs with low membrane permeability are developed, new interest is growing to enhance their intestinal permeability and bioavailability. A wide variety of nanosystems have been developed to improve drug transport and absorption. Sufficient evidence exists to suggest that nanoparticles are able to increase the transepithelial transport of drug molecules. However, key questions remained unanswered. What types of nanoparticles are more efficient? What are preclinical (or clinical) achievements of each type of nanoformulation in terms of pharmacokinetic (PK) parameters? Addressing this issue in this paper, we have reviewed the current literature regarding permeability enhancement, permeability assessment methods and changes in PK parameters following administration of various nanoformulations. Although permeability enhancement by various nanoformulations holds great promise for oral drug delivery, many challenges still need to be addressed before development of more clinically successful nanoproducts.