Fabrication of rosuvastatin-loaded polymeric nanocapsules: a promising modality for treating hepatic cancer delineated by apoptotic and cell cycle arrest assessment.

Nanotechnology has provided several advantages for the treatment of cancer. Polymeric nanocapsules (PNCs) were proven promising in the treatment of different cancer types, such as hepatic cancer. Meanwhile, the exploration of novel indications of old molecules with the purpose of cancer treatment has been widely reported. Among the promising therapeutic moieties, rosuvastatin (RV) was delineated as a potential anticancer drug. Hence, the target of the presented manuscript was to develop PNCs loaded with RV to overcome its delivery challenges and augment its anticancer activity. RV PNCs were fabricated by the nanoprecipitation method using poly-lactide-co-glycolide (PLGA) polymer, and were characterized for the size, polydispersity index (PDI), charge, entrapment efficiency EE%, in vitro release, stability, and morphology. Furthermore, their anticancer activity was tested on HepG2 cells using MTT assay, followed by elucidating the cytotoxic activity using flow cytometry. Results showed that RV PNCs displayed particle size ranging from 186 to 239 nm, average PDI, and negative zeta potential with sufficient stability for 3 months. PNCs were able to load RV at high EE% reaching 82.6% and sustain its release for eight hours. RV PNCs were superior in their anticancer activity on HepG2 cells, as delineated from the viability study and further elucidated by enhanced apoptosis in addition to cell cycle arrest at G2/M phase, suggesting their promise in treatment of hepatic cancer.

Passively Targeted Curcumin-Loaded PEGylated PLGA Nanocapsules for Colon Cancer Therapy In Vivo.

Clinical applications of curcumin for the treatment of cancer and other chronic diseases have been mainly hindered by its short biological half-life and poor water solubility. Nanotechnology-based drug delivery systems have the potential to enhance the efficacy of poorly soluble drugs for systemic delivery. This study proposes the use of poly(lactic-co-glycolic acid) (PLGA)-based polymeric oil-cored nanocapsules (NCs) for curcumin loading and delivery to colon cancer in mice after systemic injection. Formulations of different oil compositions are prepared and characterized for their curcumin loading, physico-chemical properties, and shelf-life stability. The results indicate that castor oil-cored PLGA-based NC achieves high drug loading efficiency (≈18% w(drug)/w(polymer)%) compared to previously reported NCs. Curcumin-loaded NCs internalize more efficiently in CT26 cells than the free drug, and exert therapeutic activity in vitro, leading to apoptosis and blocking the cell cycle. In addition, the formulated NC exhibits an extended blood circulation profile compared to the non-PEGylated NC, and accumulates in the subcutaneous CT26-tumors in mice, after systemic administration. The results are confirmed by optical and single photon emission computed tomography/computed tomography (SPECT/CT) imaging. In vivo growth delay studies are performed, and significantly smaller tumor volumes are achieved compared to empty NC injected animals. This study shows the great potential of the formulated NC for treating colon cancer.

Novel green-based polyglycerol polymeric nanoparticles loaded with ferulic acid: A promising approach for hepatoprotection.

In the pursuit of eco-friendly and sustainable materials, polyglycerol diacid polymers hold immense promise for drug delivery compared to those derived from fossil fuels. Harnessing this potential, we aimed to prepare nanoparticles (NPs) derived from sustainable polymers, loaded with ferulic acid (FA), a natural polyphenolic compound known for its shielding effect against liver-damaging agents, including carbon tetrachloride (CCl4). Glycerol was esterified with renewable monomers, such as succinic acid, adipic acid, and/or FA, resulting in the creation of a novel class of polyglycerol diacid polymers. Characterization via Fourier-transform infrared spectroscopy and nuclear magnetic resonance confirmed the successful synthesis of these polymers with <7 % residual monomers. FA-loaded NPs were fabricated using the newly synthesized polymers. To further augment their potential, the NPs were coated with chitosan. The chitosan-coated NPs boasted an optimal PS of 290 ± 5.03 nm, showing superior physical stability, and a commendable EE% of 58.79 ± 0.43%w/v. The cytotoxicity was examined on fibroblast cells using the SRB assay. In-vivo experiments employing a CCl4-induced liver injury model yielded compelling evidence of the heightened hepatoprotective effects conferred by chitosan-coated particles. This demonstrates the benefits of incorporating sustainable polymers into innovative composites for efficient drug delivery, indicating their potential for creating versatile platforms for various therapeutic applications.

Gamma oryzanol loaded into micelle-core/chitosan-shell: from translational nephroprotective potential to emphasis on sirtuin-1 associated machineries.

Gamma oryzanol (ORZ) is a nutraceutical that is poorly water soluble with poor intestinal absorption. In the current work, ORZ was nanoformulated into uncoated and chitosan coated micelles based on methoxy-poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) and poly(ε-caprolactone)-b-methoxy-poly(ethylene glycol)-b-poly(ε-caprolactone) (PCL-PEG-PCL) copolymers for augmenting ORZ oral delivery. The physicochemical properties, morphological study, in-vitro release and safety of the nanoplaforms were determined. Importantly, the nephroprotective competence of the nanoplaforms was analyzed against acute kidney injury (AKI) rat model and the sirtuin-1 associated machineries were assessed. The results revealed that the micelles exerted particle size (PS) from 97.9 to 117.8 nm that was markedly increased after chitosan coating. The reversal of zeta potential from negative to highly positive further confirmed efficient coating. In vitro release profiles demonstrated prolonged release pattern. The nanoforms conferred higher cell viability values than free ORZ on Vero cell line. The designed micelles displayed augmented nephroprotection compared to free ORZ with the supremacy of CS coated micelles over uncoated ones in restoring kidney parameters to normal levels. The attenuated AKI was fulfilled via the modulation of sirtuin-1 signaling pathways translated by restoring the histological features, increasing renal antioxidant states, renal autophagy and decreasing renal inflammation and renal apoptosis. These outcomes confirmed that surface modification with chitosan had a considerable leverage on micelles safety, release behavior and in vivo performance.

Nose-to-brain delivery of 18ß-Glycyrrhetinic acid using optimized lipid nanocapsules: A novel alternative treatment for Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder and the most relevant form of dementia affecting people worldwide. AD was reported to be associated with increased oxidative stress ending up with neuronal damage. 18ß-Glycyrrhetinic acid (GA), triterpenoid aglycone of glycyrrhizin, was reported for its powerful antioxidant activities. However, its high molecular weight and lipophilicity are two major obstacles that limit its use and cause very low brain bioavailability. The aim of the present study was to formulate the GA in lipid nanocapsules (LNCs) for enhanced nose-to-brain delivery, as well as to elucidate its potential neuroprotective effect in AD. The optimized GA-loaded LNCs exhibited nanometric size range, good stability over 6 months, sustained drug release over 24 h and high steady state flux and permeability coefficient across nasal mucosa over 8 h. In-vivo studies were conducted on five groups; control, scopolamine (SCOP)-treated, SCOP + GA-LNCs, SCOP + oral GA suspension, and SCOP + intranasal GA suspension groups. Intranasal administration of GA-LNCs, at a reduced dose of 1 mg/kg, improved scopolamine-induced memory impairment in rats evidenced by behavioral testing, histological examination, and oxidative stress markers; catalase and superoxide dismutase. Collectively, GA-loaded LNCs (with 50 times lower dose) may provide a promising remedy for AD patients worldwide.

Ferulic acid nanocapsules as a promising treatment modality for colorectal cancer: Preparation and in vitro/in vivo appraisal.

AIMS: Ferulic acid is a polyphenolic compound with proven anticancer properties, but it suffers from low solubility and bioavailability. In the current work, polymeric and lipidic nanocapsules of ferulic acid were prepared, characterized, and tested on colorectal cancer (CRC) cell lines (HCT-116 and Caco2 cells), with mechanistic anticancer elucidation using flow cytometry. The selected NCs formulation was further tested in vivo on rats after inducing CRC using 1,2 dimethylhydrazine (DMH), followed by biochemical analysis, molecular and histological examinations. KEY FINDINGS: Results revealed that both polymeric and lipidic nanocapsules showed favorable properties, but the latter was smaller in size and presented higher cumulative percent released of FA. The lipidic nanocapsules displayed better anticancer activity than the drug on both cell lines; with apoptosis being the dominant cell death mode. The in vivo study revealed that ferulic acid lipid NCs exhibited significant antioxidant and anti-inflammatory activities. They also downregulated cyclin D1, IGF II, and VEGF, and autoregulated the apoptotic/anti-apoptotic gene BAX/Bcl-2; indicating their apoptotic and anti-angiogenic potential, which was further confirmed by histological examination. SIGNIFICANCE: Findings prove that the proposed ferulic acid lipid nanocapsules are an ideal system for treatment of CRC, and can serve as a preventive measure against metastasis.

Oleuropein as a novel topical antipsoriatic nutraceutical: formulation in microemulsion nanocarrier and exploratory clinical appraisal.

Introduction: Oleuropein is a promising nutraceutical found in abundance in olive leaf, with reported antioxidant and anti-inflammatory properties, and hence could be a valuable treatment for dermatological diseases such as psoriasis.Areas covered: In order to overcome the poor skin penetration of oleuropein, it was formulated in a microemulsion nanocarrier. The selected microemulsion formulation displayed a particle size of 30.25 ± 4.8 nm, zeta potential 0.15 ± 0.08 mV and polydispersity index 0.3 ± 0.08, with storage stability for 1 year in room temperature and total deposition in skin layers amounting to 95.67%. Upon clinical examination in psoriatic patients, the oleuropein microemulsion formulation was proven superior to the marketed Dermovate cream composed of clobetasol propionate, in terms of reduction of Psoriasis Area and Severity Index (PASI) scores, as well dermoscopic imaging and morphometric analysis of the psoriasis lesions, in which oleuropein microemulsion exhibited marked improvement in the clinical manifestations of psoriasis.Expert opinion: The findings of this study further prove the promising role of nutraceuticals, as well as nanoparticles in enhancing the therapeutic outcome of treatments, and open new era of applications in a variety of diseases.

Intra-articular multifunctional celecoxib loaded hyaluronan nanocapsules for the suppression of inflammation in an osteoarthritic rat model.

Direct intra-articular delivery of drugs to osteoarthritic joints offers the possibility of delivering high drug concentrations at the site of action as well as decreasing long term associated side effects after oral drug delivery. So in the current work, we aimed to improve the osteoarthritic therapeutic efficacy of the non-steroidal anti-inflammatory drug; celecoxib, through the formulation of drug loaded hyaluronan nanocapsules. The proposed formulation aimed to combine the beneficial viscosupplemental properties of hyaluronic acid with the pharmacological, anti-inflammatory, effect of celecoxib in a novel drug carrier for intra-articular delivery. The proposed nanocapsules were prepared by the nanoprecipitation method. Several formulation variables were studied aiming at optimizing the nanocapsules' size, polydispersity index and celecoxib entrapment efficiency %. The optimized hyaluronan nanocapsules formulation showed a size of 254.9 ± 3.06 nm, which is appropriate for the intra-articular delivery of celecoxib, high entrapment efficiency% of 97.98% ± 0.19, and prolonged celecoxib release for almost one week. The transmission electron microscope images revealed spherical shape of the nanocapsules with distinct shell and core structure. The in-vivo evaluation of the anti-osteoarthritic activity of the optimized hyaluronan nanocapsules formulation showed the superiority of the prepared celecoxib nanocapsules compared to celecoxib suspension in a Monoiodoacetate induced osteoarthritic rat model, regarding histological, swelling and immunohistochemical parameters of osteoarthritis.

Novel antipsoriatic fluidized spanlastic nanovesicles: In vitro physicochemical characterization, ex vivo cutaneous retention and exploratory clinical therapeutic efficacy.

Tazarotene (TAZ) is a topical synthetic retinoid used in psoriasis treatment, however, it is extremely lipophilic and exhibits skin irritation. Research is in a state of continuous advancement in the field of nanocarriers fabrication, and in this regard, we investigated the formulation of novel topically oriented nanovesicles; representing a combination of spanlastics and penetration enhancer vesicles, to be termed (fluidized-SNs). TAZ-loaded fluidized SNs were physicochemically characterized, tested for ex vivo cutaneous retention, and the selected formulation was compared with the marketed product Acnitaz® regarding clinical antipsoriatic activity. The selected fluidized-SNs enriched with 1% cineole exhibited high entrapment for TAZ (76.19%), suitable size and zeta potential of 241.5 ±â€¯5.68 nm and -36.10 ±â€¯2.50 mV respectively, and retaining of stability after refrigeration storage for one month. As hypothesized, cineole enriched fluidized-SNs exhibited remarkable TAZ deposition amounting to a total of 81.51% in the different skin layers. Upon clinical assessment, the presented formulation displayed superior traits compared to the marketed product, in terms of dermoscopic imaging, morphometric analysis of psoriatic lesions, and statistical analysis of PASI scores. Results confirmed that the prepared novel fluidized spanlastics formulation holds great promise for the treatment of psoriasis, and its benefit should futuristically be investigated in other topical diseases.

Polyethylene glycol conjugated polymeric nanocapsules for targeted delivery of quercetin to folate-expressing cancer cells in vitro and in vivo.

In this work we describe the formulation and characterization of chemically modified polymeric nanocapsules incorporating the anticancer drug, quercetin, for the passive and active targeting to tumors. Folic acid was conjugated to poly(lactide-co-glycolide) (PLGA) polymer to facilitate active targeting to cancer cells. Two different methods for the conjugation of PLGA to folic acid were employed utilizing polyethylene glycol (PEG) as a spacer. Characterization of the conjugates was performed using FTIR and (1)H NMR studies. The PEG and folic acid content was independent of the conjugation methodology employed. PEGylation has shown to reduce the size of the nanocapsule; moreover, zeta-potential was shown to be polymer-type dependent. Comparative studies on the cytotoxicity and cellular uptake of the different formulations by HeLa cells, in the presence and absence of excess folic acid, were carried out using MTT assay and Confocal Laser Scanning Microscopy, respectively. Both results confirmed the selective uptake and cytotoxicity of the folic acid targeted nanocapsules to the folate enriched cancer cells in a folate-dependent manner. Finally, the passive tumor accumulation and the active targeting of the nanocapsules to folate-expressing cells were confirmed upon intravenous administration in HeLa or IGROV-1 tumor-bearing mice. The developed nanocapsules provide a system for targeted delivery of a range of hydrophobic anticancer drugs in vivo.