Development and characterization of clay facial mask containing turmeric extract solid dispersion.

OBJECTIVE: To develop clay facial mask containing turmeric extract solid dispersion (TESD) for enhancing curcumin water solubility and permeability and to determine suitable clay based facial mask. METHODS: The TESD were prepared by solvent and melting solvent method with various TE to polyvinylpyrrolidone (PVP) K30 mass ratios. The physicochemical properties, water solubility, and permeability were examined. The effects of clay types on physical stability of TESD, water adsorption, and curcumin adsorption capacity were evaluated. RESULTS: The TESD prepared by solvent method with a TE to PVP K30 mass ratio of 1:2 showed physically stable, dry powders, when mixed with clay. When TESD was dissolved in water, the obtained TESD micelles showed spherical shape with mean size of ∼100 nm resulting in a substantial enhancement of curcumin water solubility, ∼5 mg/ml. Bentonite (Bent) and mica (M) showed the highest water adsorption capacity. The TESD's color was altered when mixed with Bent, titanium dioxide (TiO2) and zinc oxide (ZnO) indicating curcumin instability. Talcum (Talc) showed the greatest curcumin adsorption followed by M and kaolin (K), respectively. Consequently, in vitro permeation studies of the TESD mixed with Talc showed lowest curcumin permeation, while TESD mixed with M or K showed similar permeation profile as free TESD solutions. The developed TESD-based clay facial mask showed lower curcumin permeation as compared to those formulations with Tween 80. CONCLUSION: The water solubility and permeability of curcumin in clay based facial mask could be improved using solid dispersion technique and suitable clay base composed of K, M, and Talc.

Mucoadhesive nanostructured lipid carriers (NLCs) as potential carriers for improving oral delivery of curcumin.

PURPOSE: To examine effects of polymer types on the mucoadhesive properties of polymer-coated nanostructured lipid carriers (NLCs). Experiment: Curcumin-loaded NLCs were prepared using a warm microemulsion technique followed by coating particle surface with mucoadhesive polymers: polyethylene glycol400 (PEG400), polyvinyl alcohol (PVA), and chitosan (CS). The physicochemical properties and entrapment efficacy were examined. In vitro mucoadhesive studies were assessed by wash-off test. In addition, the stability of mucoadhesive NLCs in gastrointestinal fluids and the pattern of drug release were also investigated. FINDINGS: The obtained nanoparticles showed spherical shape with size ranging between 200 nm and 500 nm and zeta potential between -37 and -9 mV depending on the type of polymer coating. Up to 80% drug entrapment efficacy was observed. In vitro mucoadhesive studies revealed that PEG-NLCs and PVA-NLCs were adhered strongly to freshly porcine intestinal mucosa, more than 2-fold mucoadhesive compared to CS-NLCs and uncoated-NLCs. The particle size of all polymer-coated NLCs could be maintained in both simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) suggesting good physical stability in physiological fluid. In contrast, uncoated-NLCs showed particle aggregation in SGF. In vitro dissolution studies revealed a fast release characteristic.

Crosslinked chitosan-dextran sulfate nanoparticle for improved topical ocular drug delivery.

PURPOSE: To examine the benefits of chitosan-dextran sulfate nanoparticles (CDNs) as a topical ocular delivery system with lutein as a model drug. METHODS: CDNs were developed by polyelectrolyte complexation of positively charged chitosan (CS) and negatively charged dextran sulfate (DS). 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and polyethylene glycol 400 (PEG400) were used as co-crosslinking and stabilizing agents, respectively. The influence of these on the properties of CDNs, including drug release and mucoadhesiveness, was examined. The chemical stability of lutein in CDNs (LCDNs) was also examined. RESULTS: Typically, LCDNs showed a spherical shape, possessing a mean size of ~400 nm with a narrow size distribution. The entrapment efficiency of lutein was in the range of 60%-76%. LCDNs possessing a positive surface charge (+46 mV) were found to be mucoadhesive. The release profile of LCDNs followed Higuchi's square root model, suggesting drug release by diffusion from the polymer matrix. Lutein in LCDNs showed increased chemical stability during storage compared to its solution form. CONCLUSIONS: These characteristics of CDNs make them suitable for drug delivery to the ocular surface.

Development of Pasteurella multocida-loaded microparticles for hemorrhagic septicemia vaccine.

In this study, Pasteurella multocida-loaded alginate microparticles (MPs) for subcutaneous vaccination was developed by emulsification-cross-linking technique. Formulation parameter was varied as a ratio of polymer and bacterin. Optical microscopy revealed spherical particles with uniformly distribution. A mean particle size of approximately 6 µm has been successfully constructed using simple mixer and ultrasonic probe. The zeta potential of the MPs showed negatively charge of approximately -23 mV determined by Zeta Pals® analyzer. The entrapment efficiency and the in vitro bacterin released profile could be controlled by varying the amount of alginate. The high entrapment efficiency up to 69% was achieved with low concentration of alginate. The MPs possessed a slow bacterin release profile, up to 30 days. In vivo safety and potency tests were proved that the alginate MPs were safe and induced protective immunity in mice. In addition, after storage for 6 months at either 4 °C or room temperature, the protective immunity in mice was maintained.

Mucoadhesive polyethylenimine-dextran sulfate nanoparticles containing Punica granatum peel extract as a novel sustained-release antimicrobial.

Mucoadhesive polyethylenimine-dextran sulfate nanoparticles (PDNPs) were developed for local oral mucosa delivery. Punica granatum peel extract (PGE) was loaded into PDNPs for oral malodor reduction and caries prevention. PDNPs were constructed using the polyelectrolyte complexation technique employing oppositely charged polymers polyethylenimine (PEI) and dextran sulfate (DS), with PEG 400 as a stabilizer. Under optimal conditions, spherical particles of ∼ 500 nm with a zeta potential of ∼+28 mV were produced. Up to 98%, drug entrapment efficiency was observed. The mass ratio of PEI:DS played a significant role in controlling particle size and entrapment efficacy. PDNPs shown to be a good mucoadhesive drug delivery system as confirmed by ex vivo wash off test. In vitro dissolution studies revealed that PGE-loaded PDNPs manifested a prolong release characteristic with a burst release within 5 min. In addition, they remained effectively against oral bacteria.

Development and characterization of lutein-loaded SNEDDS for enhanced absorption in Caco-2 cells.

A self-nanoemulsifying drug delivery system (SNEDDS) has been developed for enhanced oral bioavailability of lutein. Its permeation enhancement has been evaluated using monolayers of Caco-2 cells. SNEDDS is composed of a mixture of Lexol® and Emulmetik® 900, Labrasol®, and Tween 80 as oil, surfactant and co-surfactant, respectively. Upon dilution of lutein-loaded SNEDDS with water, a nanoemulsion was obtained in <10 s with spherical droplets of 40-150 nm in diameter. The zeta potential was in the range of -19 to -32 mV. Increasing the ratio of surfactant to co-surfactant decreased the mean droplet size. Dissolution studies showed that lutein was released rapidly (<5 min) from SNEDDS into 0.1 N HCl and pH 6.8 phosphate buffer solution without any aggregation. In vitro studies using Caco-2 cells revealed that lutein-loaded SNEDDS showed shorter lag time and greater (2-fold) cellular accumulation compared with the lutein dispersion.

Injectable vancomycin-loaded silk fibroin/methylcellulose containing calcium phosphate-based in situ thermosensitive hydrogel for local treatment of osteomyelitis: Fabrication, characterization, and in vitro performance evaluation.

The conventional treatment of osteomyelitis with antibiotic-loaded nondegradable polymethylmethacrylate (ATB-PMMA) beads has certain limitations, including impeded bone reconstruction and the need for secondary surgery. To overcome this challenge, this study aimed to develop and characterize an injectable vancomycin-loaded silk fibroin/methylcellulose containing calcium phosphate-based in situ thermosensitive hydrogel (VC-SF/MC-CAPs). The VC-SF/MC-CAPs solution can be easily administered at room temperature with a low injectability force of ≤30 N and a high vancomycin (VC) content of ~96%. Additionally, at physiological temperature (37 °C), the solution could transform into a rigid hydrogel within 7 minutes. In vitro drug release performed under both physiological (pH 7.4) and infection conditions (pH 4.5) revealed a prolonged release pattern of VC-SF/MC-CAPs following the Peppas-Sahlin kinetic model. In addition, the released VC from VC-SF/MC-CAPs hydrogels exhibited antibacterial activity against Staphylococcus aureus for a period exceeding 35 days, as characterized by the disk diffusion assay. Furthermore, at pH 7.4, the VC-SF/MC-CAPs demonstrated >60% degradation within 35 days. Importantly, when exposed to physiological pH conditions, CAPs are transformed into bioactive hydroxyapatite, which benefits bone formation. Therefore, VC-SF/MC-CAPs showed significant potential as a local drug delivery system for treating osteomyelitis.

Mucoadhesive Hybrid System of Silk Fibroin Nanoparticles and Thermosensitive In Situ Hydrogel for Amphotericin B Delivery: A Potential Option for Fungal Keratitis Treatment.

The purpose of this work was to investigate the feasibility of a novel ophthalmic formulation of amphotericin B-encapsulated silk fibroin nanoparticles incorporated in situ hydrogel (AmB-FNPs ISG) for fungal keratitis (FK) treatment. AmB-FNPs ISG composites were successfully developed and have shown optimized physicochemical properties for ocular drug delivery. Antifungal effects against Candida albicans and in vitro ocular irritation using corneal epithelial cells were performed to evaluate the efficacy and safety of the composite formulations. The combined system of AmB-FNPs-ISG exhibited effective antifungal activity and showed significantly less toxicity to HCE cells than commercial AmB. In vitro and ex vivo mucoadhesive tests demonstrated that the combination of silk fibroin nanoparticles with in situ hydrogels could enhance the adhesion ability of the particles on the ocular surface for more than 6 h, which would increase the ocular retention time of AmB and reduce the frequency of administration during the treatment. In addition, AmB-FNP-PEG ISG showed good physical and chemical stability under storage condition for 90 days. These findings indicate that AmB-FNP-PEG ISG has a great potential and be used in mucoadhesive AmB eye drops for FK treatment.

Fibroin and fibroin blended three-dimensional scaffolds for rat chondrocyte culture.

BACKGROUND: In our previous study, we successfully developed 3-D scaffolds prepared from silk fibroin (SF), silk fibroin/collagen (SF/C) and silk fibroin/gelatin (SF/G) using a freeze drying technique. The blended construct showed superior mechanical properties to silk fibroin construct. In addition, collagen and gelatin, contain RGD sequences that could facilitate cell attachment and proliferation. Therefore, in this study, the ability of silk fibroin and blended constructs to promote cell adhesion, proliferation and production of extracellular matrix (EMC) were compared. METHODS: Articular chondrocytes were isolated from rat and cultured on the prepared constructs. Then, the cell viability in SF, SF/C and SF/G scaffolds was determined by MTT assay. Cell morphology and distribution were investigated by scanning electron microscopy (SEM) and histological analysis. Moreover, the secretion of extracellular matrix (ECM) by the chondrocytes in 3-D scaffolds was assessed by immunohistochemistry. RESULTS: Results from MTT assay indicated that the blended SF/C and SF/G scaffolds provided a more favorable environment for chondrocytes attachment and proliferation than that of SF scaffold. In addition, scanning electron micrographs and histological images illustrated higher cell density and distribution in the SF/C and SF/G scaffolds than that in the SF scaffold. Importantly, immunohistochemistry strongly confirmed a greater production of type II collagen and aggrecan, important markers of chondrocytic phenotype, in SF blended scaffolds than that in the SF scaffold. CONCLUSION: Addition of collagen and gelatin to SF solution not only improved the mechanical properties of the scaffolds but also provided an effective biomaterial constructs for chondrocyte growth and chondrocytic phenotype maintenance. Therefore, SF/C and SF/G showed a great potential as a desirable biomaterial for cartilage tissue engineering.

Calcium phosphate incorporated in silk fibroin/methylcellulose based injectable hydrogel: Preparation, characterization, and in vitro biological evaluation for bone defect treatment.

Bone defect is still a challenging problem in orthopedic practice. Injectable bone substitutes that can fill different geometry of bone defect and improve biological environment for bone regeneration are attracting attention. Herein, silk fibroin (SF) is noticeable polymer regarding its biocompatible and biodegradable properties. Thus, the calcium phosphate particles incorporated in silk fibroin/methylcellulose (CAPs-SF/MC) and only methylcellulose (CAPs-MC) hydrogels are developed and compared their physicochemical properties. Both CAPs-hydrogels solutions can be administered with a low injectability force of ~6 N, and they require ~40-min to change to hydrogel at physiological temperature (37°C). The CAPs are evenly distributed throughout the hydrogel matrix and are capable transformed to bioactive hydroxyapatite at pH 7.4. The CAPs in CAPs-SF/MC have a smaller size than those in CAPs-MC. Moreover, CAPs-SF/MC exhibit gradual degradation, as prediction of the degradation mechanism by the Peppas-Sahlin model and show a greater ability to sustain CAPs release. CAPs-SF/MC has good biocompatibility with less cytotoxicity in a dose-dependent manner on mouse preosteoblast cell line (MC3T3-E1) when compared to CAPs-MC. CAPs-SF/MC hydrogels also have better possibility for promoting cell proliferation and differentiation. In conclusion SF incorporated into composite injectable hydrogel potentially improve biological characteristics and may provide clinical advantages.

A solid lipid particle formulation of long pepper extract reduces pain and astrocyte activation in a rat model of neuropathic pain.

OBJECTIVES: To investigate the effects of solid lipid microparticle (SLM) creams containing a long pepper extract (LPE) or piperine on neuropathy-related pain and the expression of glial fibrillary acidic protein (GFAP) as a measure of astrogliosis. METHODS: Neuropathic pain in male Spraque Dawley rats was induced by sciatic nerve ligation (SNL) and followed by treatment with LPE-SLM, piperine-SLM, capsaicin or vehicle creams. The pain score was assessed by thermal hyperalgesia test. The GFAP expression in the spinal cord was determined by immunohistochemistry. RESULTS: Pain scores were significantly increased after SNL and decreased when treated by LPE-SLM. The number of GFAP immunopositive cells was significantly increased in the SNL rats. Treated by LPE-SLM and capsaicin creams resulted in a significant reduction of the number of GFAP immunopositive cells. The LPE-SLM treated rats showed greater effects than the piperine and capsaicin preparations. CONCLUSIONS: The LPE-SLM cream has a potential effect on pain attenuation via a decrease of spinal astrocyte activation-related mechanism. The LPE in SLM preparation could provide an alternative therapeutic strategy for treating neuropathic pain.

Effects of silk sericin on the proliferation and apoptosis of colon cancer cells.

Sericin is a silk protein woven from silkworm cocoons (Bombyx mori). In animal model, sericin has been reported to have anti-tumoral action against colon cancer. The mechanisms underlying the activity of sericin against cancer cells are not fully understood. The present study investigated the effects of sericin on human colorectal cancer SW480 cells compared to normal colonic mucosal FHC cells. Since the size of the sericin protein may be important for its activity, two ranges of molecular weight were tested. Sericin was found to decrease SW480 and FHC cell viability. The small sericin had higher anti-proliferative effects than that of the large sericin in both cell types. Increased apoptosis of SW480 cells is associated with increased caspase-3 activity and decreased Bcl-2 expression. The anti-proliferative effect of sericin was accompanied by cell cycle arrest at the S phase. Thus, sericin reduced SW480 cell viability by inducing cell apoptosis via caspase-3 activation and down-regulation of Bcl-2 expression. The present study provides scientific data that support the protective effect of silk sericin against cancer cells of the colon and suggests that this protein may have significant health benefits and could potentially be developed as a dietary supplement for colon cancer prevention.

Trends in advanced oral drug delivery system for curcumin: A systematic review.

Although curcumin is globally recognized for its health benefits, its clinical application has been restricted by its poor aqueous solubility and stability. To overcome these limitations, nanocarrier-based drug delivery systems (NDS) are one of the most effective approaches being extensively explored over the last few decades to improve curcumin's physicochemical and pharmacological effects. Various NDS could provide productive platforms for addressing the formulation challenge of curcumin, but evidence of such systems has not been summarized. This study aimed to systematically review current evidence of lipid and polymer-based NDS for an oral delivery of curcumin focusing on in vivo models and clinical studies. Among the 48 included studies, 3 studies were randomized controlled clinical trials, while 45 studies were animal models. To date, only five curcumin NDS have been studied in healthy volunteers: γ-cyclodextrin, phytosome, liposome, microemulsion and solid dispersion, while most curcumin NDS have been studied in animal models. Most included studies found that NDS could increase oral bioavailability of curcumin as compared to free curcumin. In conclusion, this systematic review showed evidence of the positive effect of NDS for enhancement of oral bioavailability of curcumin. EXECUTIVE SUMMARY: Curcumin is globally recognized for its health benefits, but its clinical application has been limited by its poor aqueous solubility and stability, which causes poor absorption in the gastrointestinal tract (GI tract) via oral administration. Nanocarrier-based drug delivery systems (NDS) are considered as a productive platform to solve the formulation challenge of curcumin, but evidence of such systems has not been summarized. This study aimed to systematically review current evidence of lipid and polymer-based NDS for an oral delivery of curcumin focusing on in vivo models and clinical studies. Overall, most studies found that all studied NDS could increase the absorption of curcumin as compared to free curcumin. Curcumin was rapidly absorbed and exhibited a long residence time after oral administration of curcumin NDS. In summary, this systematic review showed positive impacts of NDS for enhancement of oral absorption of curcumin.

Effects of curcumin and γ-oryzanol solid dispersion on the brain of middle-aged rats.

Oxidative stress is one of the major factors that contributes to brain deterioration in the elderly. Oxidation causes molecular alterations, structural damage, and brain dysfunction, which includes cognitive impairment. Memory loss can begin in middle-aged individuals, so prevention of brain deterioration before aging is important. Several studies have reported that curcumin and γ-oryzanol exhibits anti-oxidant and anti-inflammatory properties. However, curcumin and γ-oryzanol exhibit low aqueous solubility. Thus, a solid dispersion technique was used to prepare curcumin and γ-oryzanol to enhance their solubility and stability. This study aims to evaluate the effects and mechanisms of γ-oryzanol solid dispersion (GOSD) and curcumin solid dispersion (CURSD) on learning and memory in six groups of male rats (n=5/group). Group one was the adult control consisting of 6-week old male rats, and the remaining five groups consisted of 42-week (middle-aged) male rats. The groups were labeled as the control group, the GO group (GOSD 10 mg/kg·BW), the Cur group (CURSD 50 mg/kg·BW), the GO-LCur group (GOSD 10 mg/kg·BW plus CURSD 25 mg/kg·BW), and the GO-HCur group (GOSD 10 mg/kg·BW plus CURSD 50 mg/kg·BW). Substances were administrated by oral gavage once daily for 42 consecutive days. The GO-HCur group exhibited significantly increased learning and memory performance in a Morris water maze and in reacting to a spontaneous tendency novel object test. The rats also exhibited decreased levels of lipid peroxidation, increased superoxide dismutase levels, glutathione peroxidase levels, catalase activity, and enhanced c-Fos expression both in the hippocampus and prefrontal cortex. The results indicated that GOSD 10 mg/kg plus CURSD 50 mg/kg was able to enhance learning and memory performance in the middle-aged rats.

Development of Metronidazole-loaded In situ Thermosensitive Hydrogel for Periodontitis Treatment

Objectives: Periodontal treatment focuses on the thorough removal of specific periodontal pathogens, mainly anaerobic Gram-negative bacteria, by mechanical scaling and root planning. In case the periodontal abscess is detected after treatment, a high dose of antimicrobial agents is commonly applied via oral administration. However, this approach increases the risk of antibiotic resistance and systemic side effects and decreases efficacy. To overcome the aforementioned issues, this study focused on the development of thermosensitive hydrogel to deliver the antibiotic drug metronidazole (MTZ) directly and locally to the oral infection site. Materials and Methods: The thermosensitive hydrogels were prepared by blending 28% w/v Pluronic F127 with various concentrations of methylcellulose (MC) and silk fibroin (SF). The gel properties, such as sol-gel transition time, viscosity, and gel strength, were investigated. The drug dissolution profiles, together with their theoretical models and gel dissolution characteristics, were also determined. Results: All hydrogel formulations exhibited sol-gel transitions at 37°C within 1 min. An increase in MC content proportionally increased the viscosity but decreased the gel strength of the hydrogel. By contrast, the SF content did not significantly affect the viscosity but increased the gel strength of the hydrogel. The thermosensitive hydrogels also showed prolonged MTZ release characteristics for 10 days in phosphate-buffered saline (PBS) at pH 6.6, which followed the Higuchi diffusion model. Moreover, MTZ-thermosensitive hydrogel exhibited delayed dissolution in PBS at 37°C for more than 9 days. Conclusion: MTZ-thermosensitive hydrogels could be considered a prospective local oral drug delivery system to achieve efficient sustained release and improve the drug pharmacological properties in periodontitis treatment.

Fibroin nanoparticles: a promising drug delivery system.

Fibroin is a dominant silk protein that possesses ideal properties as a biomaterial for drug delivery. Recently, the development of fibroin nanoparticles (FNPs) for various biomedical applications has been extensively studied. Due to their versatility and chemical modifiability, FNPs can encapsulate different types of therapeutic compounds, including small and big molecules, proteins, enzymes, vaccines, and genetic materials. Moreover, FNPs are able to be administered both parenterally and non-parenterally. This review summaries basic information on the silk and fibroin origin and characteristics, followed by the up-to-date data on the FNPs preparation and characterization methods. In addition, their medical applications as a drug delivery system are in-depth explored based on several administrative routes of parenteral, oral, transdermal, ocular, orthopedic, and respiratory. Finally, the challenges and suggested solutions, as well as the future outlooks of these systems are discussed.

Nanostructured lipid carriers: A novel hair protective product preventing hair damage and discoloration from UV radiation and thermal treatment.

The goal of this study was to investigate the protective effects of nanostructured lipid carriers (NLCs) and vitamin E loaded NLCs (Vit E-NLCs) on preventing hair damages and discoloration against UV radiation and thermal treatment. The NLCs and Vit E-NLCs were prepared using a high-pressure homogenization technique. At optimal conditions, they showed spherical particles with a mean particle size of ~140 nm and a polydispersity index of < 0.3. Up to 90% (w/w) vitamin E acetate incorporation efficacy was achieved. The protective efficacy of the model cream containing blank-NLCs (NLCs cream) or Vit E-NLCs (Vit E-NLCs cream) was investigated. Upon exposure to UV-light and heat, the FE-SEM images revealed that the hair treated with both NLCs creams showed a smoothness of hair surface similar to the virgin hair. In accordance with protein loss, they exhibited the least protein loss as compared to the hair treated with Vit-E cream, cream base and commercial products. The same trend was observed for the discoloration test, the hair treated with both NLCs creams demonstrated the lowest total color loss, as compared to other products. Comparing between two NLCs formulations, antioxidant Vit E-NLCs showed to promote the photoprotective effect against hair damage and discoloration slightly greater than blank NLCs, but it has no extra benefit for heat protection. Considered overall, the developed NLCs and Vit E-NLCs is a novel alternative for preventing hair damage and discoloration from daily UV and heat exposure.

Novel daily disposable therapeutic contact lenses based on chitosan and regenerated silk fibroin for the ophthalmic delivery of diclofenac sodium.

The aim of this study was to investigate the possibility of chitosan and regenerated silk fibroin (CS/RSF) blended films as novel biomaterials for daily disposable therapeutic contact lenses based ophthalmic drug delivery system. Diclofenac sodium (DS), a hydrophilic anti-inflammatory agent, was loaded into CS/RSF films by a soaking method. The best conditions of DS loading manifested the loading time of 2 h and pH 6.5 of drug solution. The drug loading capacity and the drug release profile could be controlled by varying the film RSF content. With increasing the film RSF content from 0 to 30%, the amount of loaded DS increased from 12 to 23 µg. Furthermore, the prolong drug released within therapeutic level was obtained with increasing the film RSF content. Consequently, a fast released characteristic within a therapeutic level up to 3 h was observed with the 100CS/0RSF film. On the other hand, the 70CS/30RSF film demonstrated a significant prolonged drug release within therapeutic level up to 11 h. In conclusion, the CS/RSF films are promising as novel biomaterials for daily disposable therapeutic contact lenses-based ophthalmic delivery.

Strategies to enhance oral delivery of amphotericin B: a comparison of uncoated and enteric-coated nanostructured lipid carriers.

The oral delivery of amphotericin B (AmB) has remained a challenge due to its low solubility, permeability, and instability in gastric acidic pH. To solve these issues, herein, we reported a novel approach of using nanostructured lipid carriers (NLCs) and NLCs coating with Eudragit®L100-55 (Eu-NLCs) for the oral delivery of AmB. This study aimed to compare their ability in protecting the drug from degradation in gastrointestinal fluids and permeation enhancement in Caco-2 cells. Uncoated NLCs and Eu-NLCs possessed a mean particle size of ∼180 and ∼550 nm, with a zeta potential of ∼-30 and ∼-50 mV, respectively. Both NLCs demonstrated an AmB entrapment efficiency up to ∼75%. They possessed significantly greater AmB water solubility than the free drug by up to 10-fold. In fasted state simulated gastric fluid, Eu-NLCs provided significantly greater AmB protection from acidic degradation than uncoated NLCs. In fasted state simulated intestinal fluid, both uncoated and Eu-NLCs showed a fast release characteristic. Caco-2 cells permeation studies revealed that uncoated NLCs provided significantly higher apparent permeation coefficient (P app) value than Eu-NLCs. Moreover, after 6 months of storage at 4 °C in the absence of light, the physicochemical stabilities of the lyophilized uncoated and Eu-NLCs could be maintained. In conclusion, the developed NLCs and Eu-NLCs could be a potential drug delivery system in improving the oral bioavailability of AmB.

Paclitaxel loaded EDC-crosslinked fibroin nanoparticles: a potential approach for colon cancer treatment.

Colon cancer is one of the most life-threatening cancers with high incidence and mortality rates. Current first-line treatments are ineffective and possess many unwanted effects. The off-label use of paclitaxel encapsulated in nanoparticles proves an innovative approach. In this study, we reported novel paclitaxel loaded EDC-crosslinked fibroin nanoparticles (PTX-FNPs) for anticancer purpose. The particles were formulated using desolvation method and the physicochemical properties were controlled favorably, including the particle size (300-500 nm), zeta potential (- 15 to + 30 mV), drug entrapment efficiency (75-100%), crystallinity, drug solubility (1- to 10-fold increase), dissolution profiles, stability (> 24 h in intravenous diluent and > 6 months storage at 4 °C). In in vitro study, all formulations showed no toxicity on the red blood cells, whereas retained the paclitaxel cytotoxicity on MCF-7 breast cancer and Caco-2 colon cancer cells. Interestingly, PTX-FNPs can be uptaken rapidly by the Caco-2 cells, consequently increased paclitaxel potency up to 10-fold compared to the free drug. Graphical abstract.