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.

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.

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.

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.

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.

Copolymeric Micelles Overcome the Oral Delivery Challenges of Amphotericin B.

Classified as a Biopharmaceutical Classification System (BCS) class IV drug, amphotericin B (AmB) has low aqueous solubility and low permeability leading to low oral bioavailability. To improve these limitations, this study investigated the potential of AmB-loaded polymeric micelles (AmB-PM) to increase intestinal absorption. AmB-PM were prepared with polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol copolymer (Soluplus®) as a polymeric carrier and used a modified solvent diffusion and microfluidics (NanoAssemblr®) method. AmB-PM have a mean particle size of ~80 nm and are mono-disperse with a polydispersity index <0.2. The entrapment efficiency of AmB was up to 95% and achieved with a high drug loading up to ~20% (w/w) with a total amount of incorporated drug of 1.08 ± 0.01 mg/mL. Importantly, compared to free drug, AmB-PM protected AmB from degradation in an acidic (simulated gastric) environment. Viability studies in Caco-2 cells confirmed the safety/low toxicity of AmB-PM. In vitro cellular absorption studies confirmed that AmB-PM increased AmB uptake in Caco-2 cells 6-fold more than free AmB (i.e., 25% compared with 4% within 30 min). Furthermore, the permeability of AmB across Caco-2 monolayers was significantly faster (2-fold) and more pronounced for AmB-PM in comparison to free drug (3.5-fold increase). Thus, the developed AmB-PM show promise as a novel oral delivery system for AmB and justifies further investigation.

Crosslinked Fibroin Nanoparticles: Investigations on Biostability, Cytotoxicity, and Cellular Internalization.

Recently, crosslinked fibroin nanoparticles (FNP) using the crosslinker 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) or the polymer poly(ethylenimine) (PEI) have been developed and showed potentials as novel drug delivery systems. Thus, this study further investigated the biological properties of these crosslinked FNP by labeling them with fluorescein isothiocyanate (FITC) for in vitro studies. All formulations possessed a mean particle size of approximately 300 nm and a tunable zeta potential (-20 to + 30 mV) dependent on the amount/type of crosslinkers. The FITC-bound FNP showed no significant difference in physical properties compared to the blank FNP. They possessed a binding efficacy of 3.3% w/w, and no FITC was released in sink condition up to 8 h. All formulations were colloidal stable in the sheep whole blood. The degradation rate of these FNP in blood could be controlled depending on their crosslink degree. Moreover, no potential toxicity in erythrocytes, Caco-2, HepG2, and 9L cells was noted for all formulations at particle concentrations of < 1 mg/mL. Finally, all FNP were internalized into the Caco-2 cells after 3 h incubation. The uptake rate of the positively charged particles was significantly higher than the negatively charged ones. In summary, the crosslinked FNP were safe and showed high potentials as versatile systems for biomedical applications.

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.

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.

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.

Amphotericin B Loaded Nanostructured Lipid Carriers for Parenteral Delivery: Characterization, Antifungal and In vitro Toxicity Assessment.

BACKGROUND: Amphotericin B (AmB) is important for the treatment of systemic fungal infections. Nowadays, only intravenous administration (IV) of AmB has been available due to its low aqueous solubility. Two forms of AmB are available. The first is Fungizone®, a mixture of AmB and sodium deoxcycholate that produces severe nephrotoxicity. The second are lipid-based formulations that reduce nephrotoxicity, but they are costly and require higher dose than Fungizone®. Thus, a cheaper delivery system with reduced AmB toxicity is required. OBJECTIVE: To develop and characterize AmB loaded-nanostructured lipid carriers (AmB-loaded NLCs) for IV administration to reduce AmB toxicity. METHODS: AmB-loaded NLCs with different solid lipids were prepared by the high-pressure homogenization technique. Their physicochemical properties and the drug release profile were examined. The molecular structure of AmB, antifungal and hemolysis activities of developed AmB-loaded NLCs were also evaluated. RESULTS: AmB-loaded NLCs ~110 to ~140 nm in diameter were successfully produced with a zeta potential of ~-19 mV and entrapment efficiency of ~75%. In vitro release showed fast release characteristics. AmB-loaded NLCs could reduce the AmB molecular aggregation as evident from the absorbance ratio of the first to the fourth peak showing a partial aggregation of AmB. This result suggested that AmB-loaded NLCs could offer less nephrotoxicity compared to Fungizone®. In vitro antifungal activity of AmB-loaded NLCs showed a minimum inhibitory concentration of 0.25 µgmL-1. CONCLUSION: AmB-loaded NLCs present high potential carriers for effective IV treatment with prolonged circulation time and reduced toxicity.

Alpha mangostin loaded crosslinked silk fibroin-based nanoparticles for cancer chemotherapy.

Silk fibroin has been utilized extensively for biomedical purposes, especially the drug delivery systems. This study introduced and characterized three novel α-mangostin loaded crosslinked fibroin nanoparticles (FNPs), using EDC or PEI as a crosslinker, for cancer treatment. All three formulas were spherical particles with a mean size of approximately 300 nm. By varying the type and/or amount of the crosslinkers, particle surface charge was controllable from -15 to +30 mV. Crosslinked FNPs exhibited higher drug entrapment efficiency (70%) and drug loading (7%) than non-crosslinked FNP. FT-IR, XRD, and DSC analytical methods confirmed that α-mangostin was entrapped in FNPs in molecular dispersion form. Compared to the free α-mangostin, the crosslinked FNPs increased the drug's solubility up to threefold. They also showed sustained release characteristics of more than 3 days, and reduced free α-mangostin hematotoxicity by 90%. The α-mangostin loaded FNPs were physicochemically stable for up to 24 h when dispersed in intravenous diluent and for at least 6 months when preserved as lyophilized powder at 4 °C. In terms of anticancer efficacy, on both Caco-2 colorectal and MCF-7 breast adenocarcinoma cell lines, all formulas maintain α-mangostin's apoptotic effect while exhibit greater cytotoxicity than the free drug. In conclusion, α-mangostin loaded crosslinked FNPs show high potential for cancer chemotherapy.

Impact of Nanostructured Lipid Carriers as an Artificial Tear Film in a Rabbit Evaporative Dry Eye Model.

PURPOSE: To characterize formulations of nanostructured lipid carriers (NLCs) as an artificial tear film and evaluate their efficacy in protecting the ocular surface epithelial cells from desiccating stress in vivo. METHODS: The physicochemical properties of NLCs, produced with components similar to the tear film such as phosphatidylcholine and squalene, were determined. In vitro cytotoxicity of NLCs was evaluated by a short-time exposure test in porcine corneal epithelial cells using a methyl thiazol diphenyl-tetrazolium bromide assay. The residence time of NLCs in rabbit eyes and the efficacy of NLCs eye drops in protecting the rabbit corneal epithelium from desiccating stress were assessed. RESULTS: Nanosized NLCs with a mean size of ∼39 ± 5 nm and a zeta potential of -30 mV could be produced and formulated into eye drop with a pH of 6.90 ± 0.01, osmolarity of 273 ± 1 mOsm/L, and surface tension of 39 ± 1 mN/m (for air interface). Eye drop formulations of NLCs were nontoxic to porcine corneal epithelial cells. NLCs drops showed higher ocular surface retention and formed a stable corneal film compared with a saline solution. Moreover, NLCs eye drops showed greater efficacy in protecting the corneal surface against desiccating stress compared with a polymer-based commercial artificial tear. CONCLUSIONS: NLCs eye drops are biocompatible in rabbit eyes and show potential as a tear replacement vehicle for the treatment of dry eye disease.

Penetration of Nile red-loaded nanostructured lipid carriers (NLCs) across the porcine cornea.

Nile Red-loaded nanostructured lipid carriers (NR-NLCs), prepared by high-pressure homogenization technique, have been investigated for their transcorneal penetration using a confocal scanning microfluorometer (CSMF). Topical exposure of NR-NLCs led to their penetration into the epithelium and anterior stroma. The NR-NLC-40 (NR-NLCs of 40 nm) showed faster penetration compared to NR-NLC-150 (NR-NLCs of 150 nm). The surface modification of NR-NLC-40 with polyethylene glycol 400 (NR-NLC-PEG) and stearylamine (NR-NLC-SA), although did not cause any significant effect on size, resulted in an increased penetration into the epithelium concomitant with a reduced penetration into the stroma compared to the NR-NLC-40. Ex vivo mucoadhesion assay revealed that NR-NLC-PEG and NR-NLC-SA adhered more strongly to the porcine corneal surface compared to NR-NLC-40. Flow cytometry experiments with porcine corneal epithelial cells showed that NR-NLC-40 was internalized better than NR-NLC-PEG and NR-NLC-SA. These results, taken together, suggest that NLCs are potentially useful for lipophilic drug delivery to the corneal epithelium and anterior stroma without any surface modifications. However, surface modifications with polyethylene glycol 400 or stearylamine could be useful to treat ocular surface disorders.

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.

Enhanced intestinal absorption of curcumin in Caco-2 cell monolayer using mucoadhesive nanostructured lipid carriers.

This study aimed to compare the intestinal permeation of curcumin-loaded polymer coated nanostructured lipid carriers (NLCs) and uncoated NLCs using the Caco-2 cell model. The uncoated NLCs were prepared using a warm microemulsion technique, while polymer-coated NLCs were prepared with the same method but were followed by coating particle surface with polyethylene glycol (PEG) 400 or polyvinyl alcohol (PVA). After lyophilization, all formulations possessed a mean size of <400 nm with a zeta potential of ∼-30 mV and a high entrapment efficacy up to 90%. All NLCs formulation showed significantly improvement in curcumin water solubility, more than 60-folds as compared to curcumin dispersion. In addition, they could protect curcumin from degradation in basic pH, 90% curcumin remaining after 6 h incubation in culture medium. In vitro permeation studies revealed that PEG-NLCs and PVA-NLCs provided significantly higher apparent permeation coefficient (Papp ) value than uncoated NLCs. Moreover, after 6 months storage at 4 °C in the absence of sunlight, the physical, and chemical stabilities of the lyophilized curcumin-loaded polymer coated NLCs and uncoated NLCs could be maintained, i.e., the mean particle size and the amount of curcumin showed no significant changes (p > 0.05) compared to those freshly prepared formulations. Considered overall, polymer coated NLCs are an important strategy to improve the oral bioavailability of curcumin. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 734-741, 2018.