Co-delivery of gemcitabine and salinomycin in PEGylated liposomes for enhanced anticancer efficacy against colorectal cancer.

Colorectal cancer remains one of the major causes of morbidity and mortality in both developed and emerging countries. Cancer stem cells (CSCs) are a subpopulation of cells within the tumor mass harboring stem cell characteristics, considered responsible for tumor initiation, growth, relapse, and treatment failure. Lately, it has become clear that both CSCs and non-CSCs have to be eliminated for the successful eradication of cancer. Drug delivery systems have been extensively employed to enhance drug efficacy. In this study, salinomycin (SAL), a selective anti-CSC drug, and gemcitabine (GEM), a conventional anticancer drug, were co-loaded in liposomes and tested for optimal therapeutic efficacy. We employed the Design of Experiments approach to develop and optimize a liposomal delivery system for GEM and SAL. The antiproliferative effect of the liposomes was evaluated in SW-620 human colorectal cancer cells. The GEM and SAL-loaded liposomes exhibited adequate size, polydispersity, zeta potential, and drug content. The in vitro release study showed a sustained release of GEM and SAL from the liposomes over 72 h. Moreover, no sign of liposome aggregation was seen over 1 month and in a biological medium (FBS). The in vitro cytotoxic effects of the co-loaded liposomes were superior to that of single GEM either in free or liposomal form. The combination therapy using GEM and SAL co-loaded in liposomes could be a promising strategy for tackling colorectal cancer.

Curcumin-Loaded Microspheres Are Effective in Preventing Oxidative Stress and Intestinal Inflammatory Abnormalities in Experimental Ulcerative Colitis in Rats.

Curcumin's role in the treatment of ulcerative colitis (UC) has been proven by numerous studies, but its preventive administration, with the aim of reducing the remission episodes that are characteristic of this disease, must be further investigated. This study investigates the effects of a novel curcumin-loaded polymeric microparticulate oral-drug-delivery system for colon targeting (Col-CUR-MPs) in an experimental model of UC. Male Wistar rats (n = 40) were divided into five groups (n = 8), which were treated daily by oral gavage for seven days with a 2% aqueous solution of carboxymethylcellulose sodium salt (CMCNa) (healthy and disease control), free curcumin powder (reference), Col-CUR-MPs (test) and prednisolone (reference) prior to UC induction by the intrarectal administration of acetic acid (AA), followed by animal sacrification and blood and colonic samples' collection on the eighth day. Col-CUR-MPs exhibited an important preventive effect in the severity degree of oxidative stress that resulted following AA intrarectal administration, which was proved by the highest catalase (CAT) and total antioxidant capacity (TAC) levels and the lowest nitrites/nitrates (NOx), total oxidative status (TOS) and oxidative stress index (OSI) levels. Biochemical parameter analysis was supported by histopathological assessment, confirming the significant anti-inflammatory and antioxidant effects of this novel colon-specific delivery system in AA-induced rat models of UC. Thus, this study offers encouraging perspectives regarding the preventive administration of curcumin in the form of a drug delivery system for colon targeting.

Improved pharmacokinetics and reduced side effects of doxorubicin therapy by liposomal co-encapsulation with curcumin.

The goal of the current study was to investigate the pharmacokinetic profile, tissue distribution and adverse effects of long-circulating liposomes (LCL) with curcumin (CURC) and doxorubicin (DOX), in order to provide further evidence for previously demonstrated enhanced antitumor efficacy in colon cancer models. The pharmacokinetic studies were carried out in healthy rats, following the i.v. injection of a single dose of LCL-CURC-DOX (1 mg/kg DOX). For the tissue distribution study, DOX concentration in tumours, heart and liver were measured after the administration of two i.v. doses of LCL-CURC-DOX (2.5 mg/kg DOX and 5 mg/kg CURC) to Balb/c mice bearing C26 colon tumours. Markers of murine cardiac and hepatic oxidative status were determined to provide additional insights into the benefit of co-encapsulating CURC and DOX in LCL over DOX-induced adverse effects in these organs. The current study demonstrated that the liposomal association of CURC and DOX effectively improved the pharmacokinetics and biodistribution of DOX, limiting its side effects, via CURC-dependent antioxidant effects.

Liposomal Curcumin Enhances the Effect of Naproxen in a Rat Model of Migraine.

BACKGROUND Curcumin is an antioxidant that reduces inflammation and pain. This study aimed to assess the effect of pretreatment with naproxen and liposomal curcumin compared with naproxen and curcumin solution on oxidative stress parameters and pain in a rat model of migraine. MATERIAL AND METHODS Sixty-three male Wistar rats included a control group (n=9) and a rat model of migraine (n=54) induced by intraperitoneal injection of nitroglycerin (1 mg/0.1 kg). The rat model group was divided into an untreated control group (n=9), a group pretreated with naproxen alone (2.8 mg/kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with curcumin solution (1 mg/0.1 kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with curcumin solution (2 mg/0.1 kg) (n=9), a group pretreated with naproxen (2.8 mg/kg) combined with liposomal curcumin solution (1 mg/0.1 kg) (n=9) a group pretreated with naproxen (2.8 mg/kg) combined with liposomal curcumin solution (2 mg/0.1 kg) (n=9). Spectroscopy measured biomarkers of total oxidative status and nociception was tested using an injection of 1% of formalin into the rat paw. RESULTS Expression of biomarkers of oxidative stress and enhanced nociception were significantly increased following pretreatment with combined naproxen and liposomal curcumin compared with curcumin solution or naproxen alone (P<0.001). Combined curcumin solution and naproxen were more effective at a concentration of 2 mg/0.1kg for the first nociceptive phase (P<0.005). CONCLUSIONS In a rat model of migraine, combined therapy with liposomal curcumin and naproxen showed an improved antioxidant effect and anti-nociceptive effect.

Liposomal Curcumin is Better than Curcumin to Alleviate Complications in Experimental Diabetic Mellitus.

Curcumin (CC) is known to have anti-inflammatory and anti-oxidative properties and has already been tested for its efficiency in different diseases including diabetes mellitus (DM). New formulations and route administration were designed to obtain products with higher bioavailability. Our study aimed to test the effect of intraperitoneal (i.p.) administration of liposomal curcumin (lCC) as pre-treatment in streptozotocin(STZ)-induced DM in rats on oxidative stress, liver, and pancreatic functional parameters. Forty-two Wistar-Bratislava rats were randomly divided into six groups (seven animals/group): control (no diabetes), control-STZ (STZ-induced DM -60 mg/100g body weight a single dose intraperitoneal administration, and no CC pre-treatment), two groups with DM and CC pre-treatment (1mg/100g bw-STZ + CC1, 2 mg/100g bw-STZ + CC2), and two groups with DM and lCC pre-treatment (1 mg/100g bw-STZ + lCC1, 2 mg/100g bw-STZ + lCC1). Intraperitoneal administration of Curcumin in diabetic rats showed a significant reduction of nitric oxide, malondialdehyde, total oxidative stress, and catalase for both evaluated formulations (CC and lCC) compared to control group (p < 0.005), with higher efficacy of lCC formulation compared to CC solution (p < 0.002, excepting catalase for STZ + CC2vs. STZ + lCC1when p = 0.0845). The CC and lCC showed hepatoprotective and hypoglycemic effects, a decrease in oxidative stress and improvement in anti-oxidative capacity status against STZ-induced DM in rats (p < 0.002). The lCC also proved better efficacy on MMP-2, and -9 plasma levels as compared to CC (p < 0.003, excepting STZ + CC2 vs. STZ + lCC1 comparison with p = 0.0553). The lCC demonstrated significantly better efficacy as compared to curcumin solution on all serum levels of the investigated markers, sustaining its possible use as adjuvant therapy in DM.

A Novel Concept of Nano-Enhanced Phase Change Material.

In the actual context of growing concerns over sustainability and energy efficiency, Phase Change Materials (PCMs) have gained attention as promising solutions for enhancing energy storage and release efficiency. On another hand, materials based on graphene oxide (GO) have proven antibacterial activity, biocompatibility, efficiency in microbial growth inhibition, and pollutant removal. Integrating nanoparticles into PCMs and creating Nano-Enhanced Phase Change Materials (NEPCMs) have opened new horizons for optimizing the performance of these systems and sustainable development. The key objective of this work is to gain insight into NECPMs, which are used in solar wall systems to enhance solar energy storage. Paraffin RT31 was mixed with Cu nanoparticles, graphene oxide (GO), and Cu-decorated GO (Cu@GO) at loading ratios ranging from 1% to 4% (w/w nanoparticles with respect to RT31). The compositions were characterized through Differential Scanning Calorimetry (DSC) and rheology tests. The decoration of the carbon-based nanoparticles was performed using the ultrasonication procedure, and the decoration efficiency was confirmed through X-ray Photoelectron Spectroscopy (XPS). The rheologic measurements were performed to correlate the flow behavior of the NEPCM with their composition at various temperatures. The study methodically investigated these composites' latent heat values, phase change peak temperatures, and solidification phase change temperatures. Compared to pure paraffin, the solidification of the formulations obtained using Cu@GO exhibits the largest increase in latent heat, with a 12.07% growth at a concentration of 2%. Additionally, at a 4% concentration of NEPCM, the largest increase in thermal conductivity was attained, namely 12.5%.

Exploring Vacuum Compression Molding as a Preparation Method for Flexible-Dose Pediatric Orodispersible Films.

In recent years, solid dosage forms have gained interest in pediatric therapy because they can provide valuable benefits in terms of dose accuracy and stability. Particularly for orodispersible films (ODFs), the literature evidences increased acceptability and dose flexibility. Among the various available technologies for obtaining ODFs, such as solvent casting, hot-melt extrusion, and ink printing technologies, the solvent-free preparation methods exhibit significant advantages. This study investigated Vacuum Compression Molding (VCM) as a solvent-free manufacturing method for the preparation of flexible-dose pediatric orodispersible films. The experimental approach focused on selecting the appropriate plasticizer and ratios of the active pharmaceutical ingredient, diclofenac sodium, followed by the study of their impacts on the mechanical properties, disintegration time, and drug release profile of the ODFs. Additional investigations were performed to obtain insights regarding the solid-state properties. The ODFs obtained by VCM displayed adequate quality in terms of their critical characteristics. Therefore, this proof-of-concept study shows how VCM could be utilized as a standalone method for the production of small-scale ODFs, enabling the customization of doses to meet the individual needs of pediatric patients.

A quality by design approach to optimise disulfide-linked hyaluronic acid hydrogels.

In this study, the disulfide-linked hyaluronic acid (HA) hydrogels were optimised for potential application as a scaffold in tissue engineering through the Quality by Design (QbD) approach. For this purpose, HA was first modified by incorporating the cysteine moiety into the HA backbone, which promoted the formation of disulfide cross-linked HA hydrogel at physiological pH. Utilising a Design of Experiments (DoE) methodology, the critical factors to achieve stable biomaterials, i.e. the degree of HA substitution, HA molecular weight, and coupling agent ratio, were explored. To establish a design space, the DoE was performed with 65 kDa, 138 kDa and 200 kDa HA and variable concentrations of coupling agent to optimise conditions to obtain HA hydrogel with improved rheological properties. Thus, HA hydrogel with a 12 % degree of modification, storage modulus of ≈2321 Pa and loss modulus of ≈15 Pa, was achieved with the optimum ratio of coupling agent. Furthermore, biocompatibility assessments in C28/I2 chondrocyte cells demonstrated the non-toxic nature of the hydrogel, underscoring its potential for tissue regeneration. Our findings highlight the efficacy of the QbD approach in designing HA hydrogels with tailored properties for biomedical applications.

Ruxolitinib-Loaded Imprinted Polymeric Drug Reservoir for the Local Management of Post-Surgical Residual Glioblastoma Cells.

(1) Background: The current limitations of glioblastoma (GBM) chemotherapy were addressed by developing a molecularly imprinted polymer (MIP)-based drug reservoir designed for the localized and sustained release of ruxolitinib (RUX) within the tumor post-resection cavity, targeting residual infiltrative cancerous cells, with minimum toxic effects toward normal tissue. (2) Methods: MIP reservoirs were synthesized by precipitation polymerization using acrylamide, trifluoromethacrylic acid, methacrylic acid, and styrene as monomers. Drug release profiles were evaluated by real-time and accelerated release studies in phosphate-buffered solution as a release medium. The cytotoxicity of polymers and free monomers was evaluated in vitro on GBM C6 cells using the Alamar Blue assay, optical microscopy, and CCK8 cell viability assay. (3) Results: Among the four synthesized MIPs, trifluoromethacrylic acid-based polymer (MIP 2) was superior in terms of loading capacity (69.9 µg RUX/mg MIP), drug release, and efficacy on GBM cells. Accelerated drug release studies showed that, after 96 h, MIP 2 released 42% of the loaded drug at pH = 7.4, with its kinetics fitted to the Korsmeyer-Peppas model. The cell viability assay proved that all studied imprinted polymers provided high efficacy on GBM cells. (4) Conclusions: Four different drug-loaded MIPs were developed and characterized within this study, with the purpose of obtaining a drug delivery system (DDS) embedded in a fibrin-based hydrogel for the local, post-surgical administration of RUX in GBM in animal models. MIP 2 emerged as superior to the others, making it more suitable and promising for further in vivo testing.

A Quality by Design Approach in Pharmaceutical Development of Non-Viral Vectors with a Focus on miRNA.

Cancer is the leading cause of death worldwide. Tumors consist of heterogeneous cell populations that have different biological properties. While conventional cancer therapy such as chemotherapy, radiotherapy, and surgery does not target cancer cells specifically, gene therapy is attracting increasing attention as an alternative capable of overcoming these limitations. With the advent of gene therapy, there is increasing interest in developing non-viral vectors for genetic material delivery in cancer therapy. Nanosystems, both organic and inorganic, are the most common non-viral vectors used in gene therapy. The most used organic vectors are polymeric and lipid-based delivery systems. These nanostructures are designed to bind and protect the genetic material, leading to high efficiency, prolonged gene expression, and low toxicity. Quality by Design (QbD) is a step-by-step approach that investigates all the factors that may affect the quality of the final product, leading to efficient pharmaceutical development. This paper aims to provide a new perspective regarding the use of the QbD approach for improving the quality of non-viral vectors for genetic material delivery and their application in cancer therapy.

Salinomycin-Based Drug Delivery Systems: Overcoming the Hurdles in Cancer Therapy.

Cancer stem cells (CSCs) are reportedly responsible for the initiation and propagation of cancer. Since CSCs are highly resistant to conventional chemo- and radiotherapy, they are considered the main cause of cancer relapse and metastasis. Salinomycin (Sali), an anticoccidial polyether antibiotic, has emerged as a promising new candidate for cancer therapy, with selective cytotoxicity against CSCs in various malignancies. Nanotechnology provides an efficient means of delivering Sali to tumors in view of reducing collateral damage to healthy tissues and enhancing the therapeutic outcome. This review offers an insight into the most recent advances in cancer therapy using Sali-based nanocarriers.

Statins in risk-reduction and treatment of cancer.

Statins, which are competitive inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, reduce cholesterol blood levels and the risk of developing cardiovascular diseases and their related complications. In addition to this main activity, statins show pleiotropic effects such as antioxidant, anti-inflammatory and antiproliferative properties, with applications in many pathologies. Based on their antiproliferative properties, in vitro and in vivo studies have investigated their effects on various types of cancer (i.e., breast cancer, prostate cancer, colorectal cancer, ovarian cancer, lung cancer) with different genetic and molecular characteristics. Many positive results were obtained, but they were highly dependent on the physiochemical properties of the statins, their dose and treatment period. Combined therapies of statins and cytotoxic drugs have also been tested, and synergistic or additive effects were observed. Moreover, observational studies performed on patients who used statins for different pathologies, revealed that statins reduced the risk of developing various cancers, and improved the outcomes for cancer patients. Currently, there are many ongoing clinical trials aimed at exploring the potential of statins to lower the mortality and the disease-recurrence risk. All these results are the foundation of new treatment directions in cancer therapy.

Development of a Curcumin-Loaded Polymeric Microparticulate Oral Drug Delivery System for Colon Targeting by Quality-by-Design Approach.

The purpose of this study was to apply the quality-by-design (QbD) approach for the development of colon-targeted curcumin-loaded polymeric microparticles (Col-CUR-MPs). The proportion of the enterosoluble polymer (Eudragit® FS) in the polymeric matrix, curcumin concentration, and the concentration of the polymer mixture (Eudragit® FS-polycaprolactone) were identified as potential risk factors for the quality of the final product following risk assessment. The influence of these variables on the critical quality attributes (CQAs) of Col-CUR-MPs was investigated. Therefore, a central composite face experimental design was used in order to determine the functional relationships between variables and product CQAs. The obtained regression model and contour plots were used to establish the design space. Finally, the model was validated by preparing two microparticulate formulations, one corresponding to the robust setpoint from within the design space and one outside the established design space, and calculating the percentage bias between the experimental and predicted values. The in vivo study, which was conducted on a fluorescein-loaded formulation that corresponded to the robust setpoint determined by QbD and that contained a mixture of polycaprolactone and Eudragit® FS (60:40, w/w), confirmed the colon-targeting qualities of this formulation.

Co-delivery of curcumin and doxorubicin in PEGylated liposomes favored the antineoplastic C26 murine colon carcinoma microenvironment.

Our recent studies have demonstrated that the antitumor efficacy of doxorubicin (DOX), administered in long-circulating liposomes (LCL), could be considerably improved after its co-encapsulation with curcumin (CURC). Thus, the question addressed within this article is whether LCL-CURC-DOX can be exploited more efficiently than liposomal DOX for future colorectal cancer therapy. Therefore, we investigated the physicochemical and biological properties of LCL-CURC-DOX and the mechanisms of its antitumor activity in C26 murine colon carcinoma in vivo. Our results proved that the developed nanoformulation based on the co-encapsulation of CURC and DOX met the requirements of a modern drug delivery system for future cancer therapy, demonstrating enhanced antitumor activity on C26 colon carcinoma in vivo. The antitumor efficacy of LCL-CURC-DOX relied on suppressive effects on main protumor processes such as angiogenesis, inflammation, oxidative stress, invasion and resistance to apoptosis, and on the dysregulation of Th1/Th2 cell axis which favored the antineoplastic phenotype of cells in tumor microenvironment (TME). The development of multitargeted strategies aiming at stimulating antitumor effects within the tumor milieu and counteracting the escape mechanisms of cancer cells would be beneficial in the management of colon cancer in the future.

Solid Lipid Nanoparticles: Vital Characteristics and Prospective Applications in Cancer Treatment.

Cancer nanotechnology is a new field of interdisciplinary research cutting across biology, chemistry, engineering, and medicine, aiming to lead to major advances in cancer treatment. Over the past several years, solid lipid nanoparticles (SLNs) have attracted the interest of researchers due to their ability to overcome the limitations of classic chemotherapeutics. We reviewed the most recent data on the therapeutic use of SLNs in oncology, presenting their main advantages and disadvantages, along with various production methods and different routes of administration. In accordance with these aspects, the long-term physical stability, the controlled release of the loaded drugs, and the efficient targeted delivery of drugs as methods of surpassing the pharmaceutical limitations of anticancer drugs, natural products and gene therapy have been discussed. In addition, we have also emphasized briefly the crosstalk between SLNs and the new trend in oncology, immunotherapy, as future possible antineoplastic treatment, especially in melanoma. This review highlights the potential of SLNs in providing very positive perspectives for future cancer treatment by improving the efficiency of present chemotherapy and reducing its side effects. SLNs allow targeted delivery of anticancer drugs and could improve the efficiency of current chemotherapy in neoplasia.

A Quality by Design (QbD) approach to the development of a gradient high-performance liquid chromatography for the simultaneous assay of curcuminoids and doxorubicin from long-circulating liposomes.

The present study highlights the advantages of using an Analytical Quality by Design (AQbD) approach to the optimization of a high-performance liquid chromatography method for the simultaneous assay of curcumin (CUR), demetoxycurcumin (DMC), bisdemetoxycurcumin (BDMC) and doxorubicin (DOX) co-encapsulated in long circulating liposomes. Within the QbD paradigm, the present study aimed to establish the method operable design region (MODR) for the optimization of the high-performance liquid chromatography-fluorescence (HPLC-FLD) assay by means of Design of Experiments (DOE) and response surface methodology, in order to achieve a good separation and quantification of all analyzed compounds along to an acceptable analysis time. A deep understanding of the quality target product profile (QTPP) and of the analytical target profile (ATP), followed by a risk assessment for variables that affect the efficiency of the method led to the development of a precise, accurate and cost-effective method. The assay was linear over the range of 2-20 µg/ml for all investigated compounds. The intra-and inter-day precision were less than 2%, with accuracies between 97-104% of the true values. The method was successfully applied to the quantification of curcuminoids and DOX from long-circulating liposomes.

Anti-angiogenic and anti-inflammatory effects of long-circulating liposomes co-encapsulating curcumin and doxorubicin on C26 murine colon cancer cells.

BACKGROUND: Emerging treatment options for colon cancer are needed to overcome the limitations regarding the side effects of current chemotherapeutics and drug resistance. The goal of this study was to assess the antitumor actions of PEGylated long-circulating liposomes (LCL) co-delivering curcumin (CURC) and doxorubicin (DOX) on murine colon carcinoma cells (C26). METHODS: The cytotoxicity of CURC and DOX, administered alone or in combination, either in free or LCL form, was evaluated with regard to antiproliferative effects on C26 cells and to protumor processes that might be affected. RESULTS: Our results indicated that PEGylated LCL-CURC-DOX exerted strong antiproliferative effects on C26 cells, slightly exceeding those induced by free CURC-DOX, but higher than either agent administered alone in their free form. These effects of LCL-CURC-DOX were due to the inhibition of the production of angiogenic/inflammatory proteins in a NF-κB-dependent manner, but were independent of ROS production or AP-1 c-Jun activation. Notable, the anti-angiogenic actions of LCL-CURC-DOX appeared to be much stronger than those induced by the co-administration of CURC and DOX in their free form, on C26 colon cancer cells. CONCLUSION: LCL-CURC-DOX demonstrated enhanced cytotoxicity on C26 murine colon cancer cells by inhibiting the production of the majority of factors involved in tumor-associated angiogenesis and inflammation and is now being evaluated in vivo regarding its efficacy towards tumor growth in colon cancer.

The effect of intravenous administration of liposomal curcumin in addition to sumatriptan treatment in an experimental migraine model in rats.

BACKGROUND: Curcumin has antioxidative properties that could be useful in various diseases due to its ability to act on multiple targets of various cellular pathways. We aimed to assess the efficacy of liposomal curcumin compared with curcumin solution, when in addition to sumatriptan (ST) treatment, in an experimental migraine model induced with nitroglycerin (NTG) in rats. METHODS: Seven groups of 9 rats each were investigated: control group without migraine (1 mL saline solution intraperitoneal injection [ip]), control group with induced migraine, NTG+ST group (ST), NTG+ST+curcumin1 (CC1) group - 1 mg/100 g body weight (bw), NTG+ST+CC2 - 2 mg/100 g bw, NTG+ST+liposomal curcumin1 (lCC1) group - 1 mg/100 g bw, and NTG+ST+lCC2 (lCC2) group - 2 mg/100 g bw. NTG and ST were administered as 1 mL ip NTG | 1 mg/100 g bw and 1 mL ip ST | 1 mg/100 g bw, respectively. Plasma total oxidative stress (TOS), malondialdehyde (MDA), nitric oxide (NOx), thiol levels, as well as total antioxidative capacity (TAC) were assessed. The nociception process was assessed by counting the number of flinches and shakes after the formalin test. RESULTS: The plasma TOS, MDA, and NOx levels, as oxidative stress parameters, were significantly decreased in the curcumin-treated groups, especially where curcumin was in liposomal form. The thiol and TAC were also improved by the curcumin treatment, with the best results obtained for the liposomal curcumin. The closest number of flinches and shakes to the control group was obtained for the group treated with liposomal curcumin at a dose of 2 mg/100 g bw. CONCLUSION: Liposomal curcumin in a dose of 2 mg/100 g bw when in addition to ST treatment could be an optimum therapeutic strategy for migraine attacks and could represent a base for future clinical research and application.

Cutaneous wound healing using polymeric surgical dressings based on chitosan, sodium hyaluronate and resveratrol. A preclinical experimental study.

Wound healing is a complex and dynamic process that involves modifying the wound environment depending on the patient's health status. Scar formation depends on many factors that influence wound healing, are important to bear in mind because most of the negative factors involved can be stopped by implementing an adequate treatment. The consensus in wound therapy recommends dressings that should keep a moist and alkaline environment thus creating a protective barrier against mechanical stress and secondary infections, in view of promoting granulation. In the current paper, we aimed to synthesize a polymer-based sponge containing chitosan-sodium hyaluronate-resveratrol (CHR) and to evaluate its regenerative potential. The process of synthesizing the CHR polymer was described before microtomography analysis was conducted and the density and porosity of the obtained sponges was assessed. The cytotoxicity was evaluated in vitro. By undertaking the in vivo testing of the CHR polymer, we aimed to determine the CHR sponge's potential to stimulate tissue regeneration after inflicting a controlled, reproducible and measurable skin wound in an animal model. Skin punch biopsies were harvested from the healed area and were subjected to histopathological evaluation. The results obtained in this study confirmed that this polymer accelerates the formation of granulation facilitating wound healing, while also achieving a bacteriostatic outcome.

Development of antiproliferative long-circulating liposomes co-encapsulating doxorubicin and curcumin, through the use of a quality-by-design approach.

The aim of this work was to use the quality-by-design (QbD) approach in the development of long-circulating liposomes co-loaded with curcumin (CUR) and doxorubicin (DOX) and to evaluate the cytotoxic potential of these liposomes in vitro using C26 murine colon carcinoma cell line. Based on a risk assessment, six parameters, namely the phospholipid, CUR and DOX concentrations, the phospholipid:cholesterol molar ratio, the temperature during the evaporation and hydration steps and the pH of the phosphate buffer, were identified as potential risk factors for the quality of the final product. The influence of these variables on the critical quality attributes of the co-loaded liposomal CUR and DOX was investigated: particle size, zeta potential, drug loading and entrapment efficiency. For this, a 26-2 factorial design was employed to establish a proper regression model and to generate the contour plots for the responses. The obtained data served to establish the design space for which different combinations of variables yielded liposomes with characteristics within predefined specifications. The validation of the model was carried out by preparing two liposomal formulations corresponding to the robust set point from within the design space and one outside the design space and calculating the percentage bias between the predicted and actual experimental results. The in vitro antiproliferative test showed that at higher CUR concentrations, the liposomes co-encapsulating CUR and DOX had a greater cytotoxic effect than DOX-loaded liposomes. Overall, this study showed that QbD is a useful instrument for controlling and optimizing the manufacturing process of liposomes co-loaded with CUR and DOX and that this nanoparticulate system possesses a great potential for use in colon cancer therapy.