Development of posaconazole nanocrystalline solid dispersion: preparation, characterization and in vivo evaluation.

OBJECTIVE: Posaconazole (PCZ) is an antifungal drug, which acts by inhibiting the lanosterol-14α-demethylase enzyme. It is a biopharmaceutical classification system class II drug with its bioavailability being limited by poor aqueous solubility. The aim of this study was to improve the oral bioavailability of PCZ by preparing nanocrystalline solid dispersion (NCS). METHODS: PCZ-NCS was prepared by a combination of precipitation and high-pressure homogenization followed by freeze-drying. Several different surfactants and polymers were screened to produce NCS with smaller particle size and higher stability. RESULTS: The optimized NCS formulation containing 0.2% Eudragit S100 and 0.2% SLS was found to provide the average particle size of 73.31 ± 4.7 nm with a polydispersity index of 0.23 ± 0.03. Scanning electron microscopy revealed the preparation of homogeneous and rounded particles. Differential scanning calorimetry and X-ray diffraction confirmed crystalline nature of NCS. Nanonization increased the saturation solubility of PCZ by about 18-fold in comparison with the neat drug. Intrinsic dissolution study showed 93% dissolution of PCZ within the first 10 min. In vivo pharmacokinetic study in Wistar rats showed that Cmax and AUCtotal of PCZ-NCS increased by 2.58- and 2.64-fold compared to the marketed formulation. CONCLUSION: PCZ-NCS formulation presents a viable approach for enhancing the oral bioavailability of PCZ.

A pH-sensitive silica nanoparticles for colon-specific delivery and controlled release of catechin: Optimization of loading efficiency and in vitro release kinetics.

Catechin is a naturally occurring flavonoid of the flavan-3-ol subclass with numerous biological functions; however, these benefits are diminished due to several factors, including low water solubility and degradation in the stomach's harsh environment. So, this study aimed to develop an intelligent catechin colon-targeting delivery system with a high loading capacity. This was done by coating surface-decorated mesoporous silica nanoparticles with a pH-responsive enteric polymer called Eudragit®-S100. The pristine wormlike mesoporous silica nanoparticles (< 100 nm) with high surface area and large total pore volume were effectively synthesized and modified with the NH2 group using the post-grafting strategy. Various parameters, including solvent polarity, catechin-carrier mass ratio, and adsorption time, were studied to improve the loading of catechin into the aminated silica nanoparticles. Next, the negatively charged Eudragit®-S100 was electrostatically coated onto the positively charged aminated nanocarriers to shield the loaded catechin from the acidic environment of the stomach (pH 1.9) and to facilitate site-specific delivery in the acidic environment of the colon (pH 7.4). The prepared nanomaterials were evaluated using several methods, including The Brauner-Emmett-Teller, surface area analyzer, zeta sizer, Field Emission Scanning Electron Microscope, Powder X-Ray Diffraction, Fourier Transform Infrared Spectroscopy, Energy-Dispersive X-ray Spectroscopy, and Differential Scanning Calorimetry. In vitro dissolution studies revealed that Eudragit®-S100-coated aminated nanomaterials prevented the burst release of the loaded catechin in the acidic environment, with approximately 90% of the catechin only being released at colonic pH (pH > 7) with a supercase II transport mechanism. As a result, silica nanoparticles coated with Eudragit®-S100 would provide an innovative and promising approach in targeted nanomedicine for the oral delivery of catechin and related medicines for treating diseases related to the colon, such as colorectal cancer and irritable bowel syndrome.

Colon-Targeted Delivery of Indole Acetic Acid Helps Regulate Gut Motility by Activating the AHR Signaling Pathway.

Intestinal peristalsis is vital for gastrointestinal physiology and host homeostasis and is frequently dysregulated in intestinal disorders. Gut microbiota can regulate gut motility, especially through the tryptophan metabolism pathway. However, the role of indoles as microbial tryptophan metabolites in colonic function requires further exploration. Here, we show that the delivery of indole acetic acid (IAA) targeting the colon can improve gut motility by activating the aryl hydrocarbon receptor (AHR). To achieve colon-targeted delivery, Eudragit S-100 (ES) and chitosan (CS) were used as drug carriers. After optimisation, IAA-loaded ES-coated CS nanoparticles exhibited an encapsulation efficiency of 83% and a drug-loading capacity of 16%. These nanoparticles exhibited pH-dependent characteristics and remained stable in acidic conditions and the upper intestine. In simulated intestinal fluid (pH 7.4) and colonic lumen, considerable amounts of IAA were released after approximately 4 h. Compared with free IAA, the nanoparticles exerted enhanced therapeutic effects on gut movement disorders induced by loperamide. The efficacy of IAA treatment was attributable to the activation of the AHR signalling pathway and increased levels of AHR agonists. Furthermore, the oral administration of IAA-loaded nanoparticles promoted serotonin secretion and maintained the intestinal barrier function. The experimental outcomes demonstrate the efficiency of the proposed colon-specific delivery system and highlight the role of IAA, produced by gut microbiota metabolism, in regulating gut peristalsis through AHR activation.

Formulation Of Benzoyl Peroxide Microsponge-Based Transdermal Gel For Acne Infection And Its Evaluation.

BACKGROUND: Benzoyl peroxide is a peroxide with antibacterial, irritating, keratolytic, comedolytic, and anti-inflammatory properties. When benzoyl peroxide is applied topically, it breaks down and releases oxygen, which kills the germs of Propionibacterium acnes. Benzoyl peroxide's irritating impact causes an increase in epithelial cell turnover, which causes the skin to peel and aids in the healing of comedones. Treatment for acne vulgaris involves the use of benzoyl peroxide. OBJECTIVE: The research is aimed at studying the formulation of Microsponge gel preparation of benzoyl peroxide by using Carbopol 934 as a gelling agent and evaluation of microsponge gel formulation for its physicochemical properties. METHODS: Microsponges of Anti-acne agent benzoyl peroxide drug were prepared by quasi-emulsion method, and in-vitro drug release using a suitable membrane model using a simple diffusion cell. RESULT: Prior to drying, the microsponge was filtered and rinsed using distilled water. Formulation containing benzoyl peroxide and Eudragit RS100 with a ratio of 1:4 showed a high 87.5% drug content and 78.20 % yield. The drug content of the microsponge gel was found to be 84%. Microbiological study on S. aureus was conducted by the cylinder cup method and found good results. The in-vitro diffusion of microsponge formulations was sustained for 8 hours. The drug release rate for Eudragit RS-100 was reported to be 88.87% after 8 hours based on the polymer: drug ratio (4:1). CONCLUSION: The quasi-emulsion solvent diffusion method was used to successfully prepare benzoyl peroxide microsponges using Eudragit RS100, Ethyl Cellulose, and HPMC K4M as polymers. The formulations with the highest medication concentration were made with the porous polymer Eudragit RS100.

Enhancing oral delivery of plant-derived vesicles for colitis.

Plant-derived vesicles (PDVs) are attractive for therapeutic applications, including as potential nanocarriers. However, a concern with oral delivery of PDVs is whether they would remain intact in the gastrointestinal tract. We found that 82% of cabbage PDVs were destroyed under conditions mimicking the upper digestive tract. To overcome this limitation, we developed a delivery method whereby lyophilized Eudragit S100-coated cabbage PDVs were packaged into a capsule (Cap-cPDVs). Lyophilization and suspension of PDVs did not have an appreciable impact on PDV structure, number, or therapeutic effect. Additionally, packaging the lyophilized Eudragit S100-coated PDVs into capsules allowed them to pass through the upper gastrointestinal tract for delivery into the colon better than did suspension of PDVs in phosphate-buffered saline. Cap-cPDVs showed robust therapeutic effect in a dextran sulfate sodium-induced colitis mouse model. These findings could have broad implications for the use of PDVs as orally delivered nanocarriers of natural therapeutic plant compounds or other therapeutics.

Polymer Encapsulated Liposomes for Oral Co-Delivery of Curcumin and Hydroxytyrosol.

Curcumin (Cur) is a hydrophobic polyphenol from the rhizome of Curcuma spp., while hydroxytyrosol (HT) is a water-soluble polyphenol from Olea europaea. Both show outstanding antioxidant properties but suffer from scarce bioavailability and low stability in biological fluids. In this work, the co-encapsulation of Cur and HT into liposomes was realized, and the liposomal formulation was improved using polymers to increase their survival in the gastrointestinal tract. Liposomes with different compositions were formulated: Type 1, composed of phospholipids and cholesterol; Type 2, also with a PEG coating; and Type 3 providing an additional shell of Eudragit® S100, a gastro-resistant polymer. Samples were characterized in terms of size, morphology, ζ-potential, encapsulation efficiency, and loading capacity. All samples were subjected to a simulated in vitro digestion and their stability was investigated. The Eudragit®S100 coating demonstrated prevention of early releases of HT in the mouth and gastric phases, while the PEG shell reduced bile salts and pancreatin effects during the intestinal digestion. In vitro antioxidant activity showed a cumulative effect for Cur and HT loaded in vesicles. Finally, liposomes with HT concentrations up to 40 µM and Cur up to 4.7 µM, alone or in combination, did not show cytotoxicity against Caco-2 cells.

Fat fighting liraglutide based nano-formulation to reverse obesity: Design, development and animal trials.

Obesity is a metabolic disease, which is one of the major causes of morbidity and mortality, where therapeutic options are limited. Treatment of obesity is necessary as it is associated with fatal complications like diabetes mellitus, cardiovascular disease, non-alcoholic fatty liver disease, osteoarthritis, and many more. Liraglutide (Lir), a synthetic analogue of Glucagon-like Peptide-1 (GLP-1), is the FDA approved anti-obesity drug, however, its major limitation is its clinical application which needs frequent parenteral injections. To address the issue of regular injection, we have synthesized a fat fighting oral nano-formulation of liraglutide with a sustained release feature, which was evaluated against high fat diet (HFD) induced obesity in mice. Experimental obesity was induced in mice by feeding HFD for 26 weeks. Lir nanoparticles (NP) were fabricated with chitosan via ion-gelation technique and were coated with Eudragit@S100 to protect the drug in harsh gastric conditions. Physiochemical characterization of Eu-Lir-Cs-NP demonstrated a small particle size of 253.1 ± 1.21 nm with âˆ¼ 9.74 % loading and âˆ¼ 72.11 % encapsulation efficiency of the drug. In-vitro studies showed successful cellular uptake of NP in Caco-2 cells and were stable in various enteric fluid pH conditions. Eudragit@S100 coated chitosan NP were able to protect the drug from harsh gastric pH conditions with more than âˆ¼ 74% of recovery. Treatment of two weeks of liraglutide Eu-Lir-Cs-NP (0.1, 0.2 and 0.4 mg/kg, orally; twice daily) moderately reduces obesity in mice as evidenced by a reduction in the body weight, blood glucose, serum total cholesterol, serum triglyceride, serum resistin and serum insulin level of mice. In addition, significant reduction of liver weight, abdominal white adipose tissue, and hepatic oxidative stress were noted. Our results suggest that chitosan-based NP of liraglutide can be an effective and convenient formulation for the management of obesity.

Piperine-loaded nanoparticles incorporated into hyaluronic acid/sodium alginate-based membranes for the treatment of inflammatory skin diseases.

Piperine is an alkaloid mostly found in the fruits of several species of the Piper genus, and its anti-inflammatory potential is already known. However, its therapeutic applications still need to be better explored due to the low aqueous solubility of this active. To overcome this drawback, the objective of this work was to evaluate the efficiency of the nanoencapsulation of the compound as well as its incorporation into hyaluronic acid/alginate-based biomembranes. Polymeric nanoparticles composed of Eudragit S100 and Poloxamer 188 were obtained by the nanoprecipitation technique, obtaining spherical nanosized particles with an average diameter of 122.1 ± 2.0 nm, polydispersity index of 0.266, and encapsulation efficiency of 76.2 %. Hyaluronic acid/sodium alginate membranes were then prepared and characterized. Regarding permeation, a slow passage rate was observed until the initial 14 h, when an exponential increase in the recovered drug concentration began to occur. The in vivo assay showed a reduction in inflammation up to 43.6 %, and no cytotoxicity was observed. The results suggested the potential of the system developed for the treatment of inflammatory skin diseases.

Redox responsive poly(allylamine)/eudragit S-100 nanoparticles for dual drug delivery in colorectal cancer.

Herein, we report redox responsive, colon cancer targeting poly(allylamine) (PA)/eudragit S-100 (EU) nanoparticles (PAEU NPs) (≈59 nm). These disulfide crosslinked PAEU NPs are developed via air oxidation of thiolated PA and thiolated EU, eliminating the need of any external crosslinking agent for dual drug delivery. PAEU NPs can effectively encapsulate both hydrophilic doxorubicin (DOX) and hydrophobic curcumin (Cur) drug with ≈85 % and ≈97 % encapsulation efficiency respectively. Here, the combination of drugs having different anticancer mechanism offers the possibility of developing nanosystem with enhanced anticancer efficacy. The developed PAEU NPs show good colloidal stability and low drug release under physiological conditions, while high DOX (≈98 %) and Cur (≈93 %) release is observed in reducing environment (10 mM GSH). Further, DOX and Cur loaded PAEU NPs exhibit higher cancer cell killing efficiency as compared to individual free drugs. In vivo biodistribution studies with Balb/C mice display the retention of PAEU NPs in the colon region up to 24 h presenting the developed approach as an efficient way for colorectal cancer therapy.

Development of melatonin-loaded, human-serum-albumin nanoparticles formulations using different methods of preparation for ophthalmic administration.

The use of proteins such as human serum albumin (HSA) to form nanometric systems seems very promising since they are non-toxic, biodegradable and have no antigenic activity. This molecule is ideal to transport insoluble drugs such as melatonin (Mel), which has antiapoptotic and antioxidant properties and appears promising for the treatment of neurodegenerative eye diseases. The objective of this study was to obtain nanoparticulate systems loaded with Mel, improving the conventional desolvation method. Systems were stabilised using two different strategies: one through the use of Eudragit S100 as a cross-linking agent and the other through thermal stabilisation. The systems thus obtained (Np-HSA-Eu-Mel and Np-HSA-Mel, respectively) were characterised and compared in terms of physicochemical and pharmacotechnical parameters. Whitish colloidal dispersions of nanometric size (≈170 nm), spherical shape, and monodisperse population were obtained. Besides, the pH was close to neutrality reaching 20 % drug encapsulation whereas the process performance was higher than 80 %. In FT-IR studies, thermal analysis and X-ray diffraction (XRD), the incorporation of the drug in the cavities of the nanoparticles could be evidenced. Regarding the physical stability of nanoparticles, for Np-HSA-Eu-Mel instability was observed at pH > 7. However, Np-HSA-Mel was able to remain stable at different pH levels. Mel release from these systems was consequently affected, where the former released faster than the active compared to the last. On the other hand, it was observed that the drying process (lyophilization in this case) applied to the nanoparticles suspensions does not affect their original properties after redispersion over a three months period. Likewise, the formulation did not produce irritation when administered topically, whereas when administered subconjunctivally, only slight irritation was observed 24 h after administration. According to the result of this study, the Np-HSA-Mel formulation could achieve advantageous properties as a vehicle for the transport of insoluble drugs for the treatment of neurodegenerative diseases at the ocular level.

pH-Responsive Inorganic/Organic Nanohybrids System for Controlled Nicotinic Acid Drug Release.

Although nicotinic acid (NA) has several clinical benefits, its potency cannot be fully utilized due to several undesirable side effects, including cutaneous flushing, GIT-associated symptoms, etc. To overcome such issues and improve the NA efficacy, a new inorganic-organic nanohybrids system was rationally designed. For making such a hybrid system, NA was intercalated into LDH through a coprecipitation technique and then coated with Eudragit® S100 to make the final drug delivery system called Eudragit® S100-coated NA-LDH. The as-made drug delivery system not only improved the NA release profile but also exhibited good bio-compatibility as tested on L929 cells. Such an inorganic-organic nanohybrid drug delivery agent is expected to reduce the undesirable side effects associated with NA and hopefully improve the pharmacological effects without inducing any undesirable toxicity.

Development of microparticles for oral administration of Periplaneta americana extract to treat ulcerative colitis.

Ulcerative colitis (UC) is a chronic disease, which can result the inflammation of the rectum, mucosa of the colon, and submucosa. The active component such as polypeptide in Periplaneta americana, which is one of the most common insects in the nature, can be extracted to treat UC. However, the active components in Periplaneta americana extract (PAE) can be degraded in the stomach due to its extreme acidic environment and enzyme. In this study, we developed a pH-dependent drug delivery method using polymer cellulose acetate (Eudragit S100) as a carrier to deliver high concentration PAE to inflamed colon. Both in vitro and in vivo results showed the PAE-Eudragit-S100 could treat UC through delivering active drug components to colon without degradation.

Colon targeted chitosan-melatonin nanotherapy for preclinical Inflammatory Bowel Disease.

Inflammatory Bowel (IBD) is an umbrella term which includes Crohn's Disease (CD) and Ulcerative Colitis (UC). At present, therapies available for management of the UC includes, corticosteroid, immuno-suppressants and antibiotics are used for mild to moderate UC conditions which can cause nephrotoxicity, hepatotoxicity and cardiotoxicity. Hence, a novel therapeutic candidate having potent anti-inflammatory effect is urgently warranted for the management of UC. Melatonin has emerged as a potent anti-inflammatory agent. However, poor solubility limits its therapeutic potential. Therefore, colon targeted Eudragit-S-100 coated chitosan nanoparticles have been demonstrated to improve melatonin therapeutic efficacy. It was found that melatonin loaded chitosan and colon targeted chitosan nanoparticles had promising anti-inflammatory efficacy in terms of NO scavenging activity in an in-vitro LPS challenged macrophages. Also, colon targeted oral chitosan nano-formulation exhibited remarkable protection in an in vivo UC mice model by improving gross pathological parameters, histo-architectural protection, goblet cell depletion, and immune cells infiltration which can be extrapolated to clinical studies.

Formulation of Polymers-Based Methotrexate Patches and Investigation of the Effect of Various Penetration Enhancers: In Vitro, Ex Vivo and In Vivo Characterization.

The present study aimed to prepare methotrexate-loaded transdermal patches with different blends of hydrophobic and hydrophilic polymers (Eudragit S-100 and hydroxypropyl methylcellulose) at different concentrations. The polymers employed in transdermal patches formulations served as controlled agent. Transdermal patches were prepared using the solvent casting technique. The suitable physicochemical properties were obtained from the formulation F5 (HPMC and Eudragit S-100 (5:1). Various penetration enhancers were employed in different concentrations to investigate their potential for enhancing the drug permeation profile from optimized formulations. A preformulation study was conducted to investigate drug-excipient compatibilities (ATR-FTIR) and the study showed greater compatibility between drug, polymers and excipients. The prepared patches containing different penetration enhancers at different concentrations were subjected for evaluating different physicochemical parameters and in vitro drug release studies. The obtained data were added to various kinetic models, then formulated patch formulations were investigated for ex vivo permeation studies, in vivo studies and skin drug retention studies. The prepared patches showed elastic, smooth and clear nature with good thickness, drug content, % moisture uptake and weight uniformity. The prepared transdermal patches showed % drug content ranging from 91.43 ± 2.90 to 98.37 ± 0.56, % swelling index from 36.98 ± 0.19 to 75.32 ± 1.21, folding endurance from 61 ± 3.14 to 78 ± 1.54 and tensile strength from 8.54 ± 0.18 to 12.87 ± 0.50. The formulation F5, containing a greater amount of hydrophilic polymers (HPMC), showed increased drug release and permeation and drug retention when compared to other formulated transdermal patch formulations (F1-F9). No significant change was observed during a stability study for a period of 60 days. The rabbit skin samples were subjected to ATR-FTIR studies, which revealed that polymers and penetration enhancers have affected skin proteins (ceramides and keratins). The pharmacokinetic profiling of optimized formulation (F5) as well as formulations with optimized concentrations of penetration enhancers revealed Cmax ranged 167.80 ng/mL to 178.07 ± 2.75 ng/mL, Tmax was 8 h to 10 h, and t1/2 was 15.9 ± 2.11 to 21.49 ± 1.16. From the in vivo studies, it was revealed that the formulation F5-OA-10% exhibited greater skin drug retention as compared to other formulations. These results depicted that prepared methotrexate transdermal patches containing different blends of hydrophobic and hydrophilic polymers along with different penetration enhancers could be safely used for the management of psoriasis. The formulated transdermal patches exhibited sustained release of drug with good permeations and retention profile. Hence, these formulated transdermal patches can effectively be used for the management of psoriasis.

Advances in the colon-targeted chitosan based multiunit drug delivery systems for the treatment of inflammatory bowel disease.

Chitosan is the polymer of choice for delivery of the active moieties to the colon due to its cationic nature that enables strong mucosal attachment. Chitosan is explored for formulations such as pellets, beads, microspheres, nanoparticles and drug-polymer conjugates for colon targeting of various therapeutic agents in inflammatory bowel disease (IBD). The major challenge in the colonic delivery of drugs in IBD is altered physiological pH, which can be addressed via chitosan containing multiparticulate drug delivery systems owing to their biodegradability in the colon. Its ionic interaction with anionic polymers forms gastro-resistant multi-unit systems that ensures safe delivery of payloads to the colon. In contrast to commercial grade gastro-resistant polymers, chitosan has GRAS (generally regarded as safe) status that ensures safety for long-term therapy in case of chronic diseases such as IBD. Here, we review in detail essential properties of chitosan and chitosan based multiunit formulations for treatment/mitigation of IBD.

An Insight into Eudragit S100 Preserving Mechanism of Cinnarizine Supersaturation.

Generally, supersaturation of weakly basic drug solution in the gastrointestinal tract can be followed by precipitation, and this can compromise the bioavailability of drugs. The purpose of this study was to evaluate the effect of Eudragit® S100 on the pH-induced supersaturation of cinnarizine and to examine the preserving mechanism of cinnarizine supersaturation by Eudragit®. Variables, including pH of media, ionic strength, and degree of supersaturation, were studied to investigate the effects of these parameters on cinnarizine supersaturation in the presence and absence of Eudragit®. The size of the Eudragit® aggregate in solution using dynamic light scattering was determined. The effect of Eudragit® on the transport of cinnarizine through the Caco-2 membrane was also investigated. The particle size study of Eudragit® aggregates showed that the size of these aggregates become large when the pH was lowered. Supersaturation experiments also demonstrated that Eudragit® preserved higher cinnarizine supersaturation with increasing ionic strength of the solution. The phase separation behavior of cinnarizine solution as a function of the degree of the supersaturation could be readily explained by considering the drug amorphous solubility. In vitro permeation studies revealed that the rate of cinnarizine permeation across Caco-2 cells increased in the presence of Eudragit®. According to the obtained results, the aggregation status of Eudragit® and nonspecific hydrophobic cinnarizine-Eudragit® interactions seemed to be essential in determining the effect of Eudragit® on cinnarizine supersaturation.

Formulation and Characterization of Doxycycline-Loaded Polymeric Nanoparticles for Testing Antitumor/Antiangiogenic Action in Experimental Colon Cancer in Mice.

Nanotherapeutics can enhance the characteristics of drugs, such as rapid systemic clearance and systemic toxicities. Polymeric nanoparticles (PRNPs) depend on dispersion of a drug in an amorphous state in a polymer matrix. PRNPs are capable of delivering drugs and improving their safety. The primary goal of this study is to formulate doxycycline-loaded PRNPs by applying the nanoprecipitation method. Eudragit S100 (ES100) (for DOX-PRNP1) and hydroxypropyl methyl cellulose phthalate HP55 (for DOX-PRNP2) were tested as the drug carrying polymers and the DOX-PRNP2 showed better characteristics and drug release % and was hence selected to be tested in the biological study. Six different experimental groups were formed from sixty male albino mice. 1,2,-Dimethylhydrazine was used for 16 weeks to induce experimental colon cancer. We compared the oral administration of DOX-PRNP2 in doses of 5 and 10 mg/kg with the free drug. Results indicated that DOX-PRNP2 had greater antitumor activity, as evidenced by an improved histopathological picture for colon specimens as well as a decrease in the tumor scores. In addition, when compared to free DOX, the DOX-PRNP2 reduced the angiogenic indicators VEGD and CD31 to a greater extent. Collectively, the findings demonstrated that formulating DOX in PRNPs was useful in enhancing antitumor activity and can be used in other models of cancers to verify their efficacy and compatibility with our study.

Development, Characterization, and Investigation of In Vivo Targeted Delivery Efficacy of Luteolin-Loaded, Eudragit S100-Coated mPEG-PLGA Nanoparticles.

Luteolin (Lu) is a kind of flavonoid that has been proved to treat non-alcoholic fatty liver disease by alleviating intestinal microbiota disorder. In this study, luteolin was coated with methoxy poly(ethylene glycol)-poly(dl-lactide-co-glycolic acid) (mPEG-PLGA) using an emulsion solvent evaporation method, and the optimum preparation process was determined by a single-factor experiment combined with response surface methodology (RSM). Methacrylic acid-methyl methacrylate (1:2) copolymer (Eudragit S100) was then used to coat the surface of Lu/mPEG-PLGA nanoparticles. The physical parameters of Eudragit S100-coated Lu/mPEG-PLGA nanoparticles (Lu-NPs), such as appearance, particle size, potential, particle size distribution and drug release, and stability in vitro, were evaluated. In addition, its cytotoxicity in vitro, pharmacokinetics, tissue distribution, and toxicity in vivo were also studied. The results showed that the prepared Lu-NPs had uniform particle size distribution, high encapsulation efficiency, and good stability. Normal colonic epithelial cells showed good tolerance to Lu-NPs. After oral administration, the blood concentration of luteolin peaked at 8 h, and the main tissue distribution was within the colon, confirming its colon-targeted profile. Safety assessments also indicated that no significant changes were observed in main organs after administration of Lu-NPs. The use of Eudragit S100-coated Lu/mPEG-PLGA nanoparticles is a new strategy for colon-targeted delivery of luteolin that encourages luteolin to fulfill its role in the colon.

pH-sensitive nanoparticles containing 5-fluorouracil and leucovorin as an improved anti-cancer option for colon cancer.

Background: Parenteral administration of chemotherapeutic drugs, 5-fluorouracil (5-FU) and leucovorin (LV), is commonly used to treat large bowel carcinomas such as colon cancer (CC) and colorectal carcinoma (CRC). Aim: Our study aims to design a novel nanoparticulate drug-delivery vehicle for oral use capable of colon-specific release. Methods: A modified double-emulsion solvent evaporation method was used in the preparation of pH-responsive Eudargit® S100 polymeric nanoparticles, loaded with 5-FU/LV combination (5-FU/LV-loaded Eudargit S100 NPs). Results: Our optimized drug-loaded NP showed a pH-responsive drug release and exhibited significantly more cytotoxic actions in cancer-cell lines than free drugs. Conclusion: These findings open the way for conducting clinical trials for colon malignancies treated with nanoparticles.

Toltrazuril-Loaded Polymeric Nanocapsules as a Promising Approach for the Preventive Control of Coccidiosis in Poultry.

Coccidiosis is a disease caused by intracellular protozoan parasites of the genus Eimeria that affect the intestinal tract of poultry. However, strain resistance and drug residue in the carcass have drawn the attention of the productive sector. The nanotechnology can improve the biological effect of drugs, reducing of administered doses and toxic effects. Due to this, toltrazuril-load polymeric nanoparticles based on Eudragit® S100 (NCt) or poly-ε-caprolactone (LNCt) were developed to prevent coccidiosis in broilers. Nanoformulations were produced and showed homogeneous particle diameter distribution in the nanometer range (z-average and D (4.3) < 200 nm), negative zeta potential (<-8.93 mV), drug content ~100%, and encapsulation efficiency >90%. Cell viability assays using avian fibroblasts showed that LNCt presented no relevant toxicity up to 72 h. LNCt was then prophylactically administrated to chicken followed by challenge with Eimeria oocysts. The evaluation of the small intestine and cecum showed that the treatment with LNCt (3.5 mg/kg/day) in drinking water reduced the lesion scores and oocysts excretion, similar to the reference medicine containing toltrazuril (Baycox®, 7 mg/kg/day). The current study shows the potential protective use of nanoencapsulating anticoccidial drugs as a promising approach for the control of coccidiosis in poultry.