High-pressure Homogenization Method Research Articles

Preparation of cellulose nanofibrils from okara by high pressure homogenization method using deep eutectic solvents

The interest in the application of deep eutectic solvents (DES) as a green solvent has increased rapidly. The application of DES in agro-industrial okara treatment can be developed into industrialization. In order to simplify the degreasing, deproteinization and cellulose extraction steps in the process of pretreating okara cellulose, a new approach to cellulose extraction from okara via one-pot DES treatment is established. Three different complexing agents, choline salts in oxalic acid, in glycerol and in urea are studied in this work. The structure and properties of cellulose nanofibers (CNFs) prepared by high pressure homogenization following pretreatment of okara with anionic systhesized DES are investigated. The effects of different systems on the degree of microfibrillation of okara are analyzed using techniques such as SEM, FTIR, TD and DTG. The results indicate that by pretreating okara with choline chloride–oxalic acid type solvent, CNFs with average diameter of 27 nm are obtained using high pressure homogenization.

Development of Oral Lipid Based Nano-formulation of Dapagliflozin: Optimization, in vitro Characterization and ex vivo Intestinal Permeation Study.

The oral route is the most prevalent route of drug administration among various routes. Dapagliflozin is an oral hypoglycemic drug used for lowering the blood glucose level. The objective of this work is to developed and optimized dapagliflozin loaded nanostructured lipid carriers (DG-NLCs) for the improvement of oral delivery. DG-NLCs were prepared by a high-pressure homogenization method (hot) and optimized by Box-Behnken design software using lipid, surfactant, and homogenization cycle as an independent variable. DG-NLCs were evaluated for particle size (Y1), entrapment efficiency (Y2), drug release (Y3). The DG-NLCs were further evaluated for morphology, thermal and X-ray diffraction analysis, ex-vivo intestinal permeation, and stability study. Particle size (nm), entrapment efficiency (%) and drug release (%) of all seventeen formulations were found in the range of 113.71-356.22 nm, 60.43-96.54% and 63.44-83.62% respectively. Morphology of optimized formulation exhibited spherical in shape confirmed by transmission electron microscopy. Thermal and X-ray diffraction analysis of NLCs showed the drug was solubilized and lost the crystallinity. DG-NLCs-opt exhibited dual release pattern initial fast and later sustained-release (90.01±2.01% in 24 h) whereas DG-dispersion showed 31.54±1.87% release in 24 h. Korsmeyer-Peppas model was found to be the best fit model (R2=0.999). The DG-NLCs-opt exhibited significant-high (p < 0.05, 1.293 µg/cm2/h) flux than DG-dispersion (0.2683 µg/cm2/h). Apparent permeation coefficient of DG-NLCs-opt was found to be significantly higher (p < 0.05, 4.14×10-5 cm/min) than DG-dispersion (8.61×10-6 cm/min). The formulation showed no significant changes (p < 0.05) on six months of storage study at 25±2°C/60±5%RH. The finding concluded that quality by design (QbD) based lipid nanocarrier for oral delivery could be a promising approach of dapagliflozin for the management of diabetes.

Poloxamer 407 based-nanoparticles for controlled release of methotrexate.

Poloxamer 407 (P407)-based nanoparticles were produced by the high pressure homogenization method for the encapsulation and delivery of methotrexate (MTX), aiming intravenous therapeutic applications. The surface of these nanoparticles was functionalized by conjugation of P407 with folic acid (FA) or with MTX, which served as targeting ligand agents. MTX-P407 conjugate was also developed to increase the final drug cargo. Two hydrophobic derivatives of MTX, MTX di-ethylated ester (MTX-OEt) and the ionic complex MTX-dimethyldioctadecylammonium bromide (MTX-DODAB) were produced and entrapped onto P407-based nanoparticles. All formulations developed revealed a monodisperse character comprising small and narrow nanoparticles (<100nm). P407 nanoparticles (functionalized with FA) and MTX-P407 nanoparticles, both loaded with MTX-OEt, demonstrated a slow drug release profile. The effect of lipase from Aspergillus oryzae on the hydrolysis of the linkage between the P407 and MTX, and consequent MTX release profile, was also evaluated. We observed a controlled and slow release of MTX (<50% of release after 11days) in the presence of enzyme. These MTX-P407 nanoparticles loaded with MTX-OEt induced a great effect against Caco-2 cancer cells (≈40% of cell death after 72h of incubation), demonstrating higher efficiency than the free MTX at the same concentration.

A LIPOSOMAL COMPOSITION OF MUSC DEER PREPUTIAL GLAND EXTRACT AS A NEW AGENT OF ADAPTOGENIC ACTION

For the first time, a liposomal form of a new original drug based on the Siberian musk deer preputial gland extract was obtained and characterized. An effective and scalable method of high-pressure homogenization was used for preparative extraction of liposomes from musk extracts. For the obtained liposomal product, such indicators as the quality of size distribution, homogeneity and the degree of inclusion of biologically active components were characterized using the methods of dynamic light scattering, transmission microscopy, preparative and analytical chromatography and chromatography-mass spectrometry. A homogeneous dispersion of musk liposomes with a uniform size distribution was obtained, with the maximum distribution values being achieved at 50 and 240 nm. The ζ-potential of the obtained nanoparticles of –35...–47 mV confirmed a high physicochemical stability of the developed liposomal dispersion. According to the gel filtration chromatography and mass spectrometry results, the degree of inclusion of the target musk extract components in the liposomes was 55–75% in terms of steroid and total protein values. The obtained quality indicators indicate that the developed liposomal composition of musk deer extracts can be used as a high-effective natural adaptogen.

Fabrication of Second Generation Smarter PLGA Based Nanocrystal Carriers for Improvement of Drug Delivery and Therapeutic Efficacy of Gliclazide in Type-2 Diabetes Rat Model

Drug delivery and therapeutic challenges of gliclazide, a BCS class II drug used in type 2 diabetes mellitus (T2DM) can be overcome by exploring smarter carriers of second-generation nanocrystals (SGNCs). A combined method of emulsion diffusion, high-pressure homogenization and solvent evaporation method were employed in the preparation of gliclazide loaded poly (D, L-lactide-co-glycolide) (PLGA) SGNCs. Taguchi experimental design was adopted in fabrication of Gliclazide SGNc using Gliclazide -PLGA ratio at 1:0.5, 1:0.75, 1:1 with stabilizer (Poloxamer-188, PEG 4000, HPMC E15 at 0.5, 0.75, 1% w/v). The formulated gliclazide of SGNCs were investigated for physicochemical properties, in vitro drug release, and in vivo performance studies using type-2 diabetes rat model. The formulation (SGNCF1) with Drug: PLGA 1: 0.5 ratio with 0.5% w/v Poloxamer-188 produced optimized gliclazide SGNCs. SGNCF1 showed spherical shape, small particle size (106.3 ± 2.69 nm), good zeta potential (−18.2 ± 1.30 mV), small PDI (0.222 ± 0.104) and high entrapment efficiency (86.27 ± 0.222%). The solubility, dissolution rate and bioavailability of gliclazide SGNCs were significantly improved compared to pure gliclazide. The findings emphasize gliclazide SGNCs produce faster release initially, followed by delayed release with improved bioavailability, facilitate efficient delivery of gliclazide in T2DM with better therapeutic effect.

Optimization and evaluation of cyclosporine A nanosuspension stabilized by combination stabilizers using high pressure homogenization method

Optimization and evaluation of cyclosporine A nanosuspension stabilized by combination stabilizers using high pressure homogenization method

Hepato &amp; nephro protective effects of naringenin-loaded tpgs polymeric nanosuspension against cisplatin-induced toxicity

Cisplatin (Cis-Diammineplatinum (II) dichloride/CIS) is one of the most potent chemotherapeutic agents widely used in treatment of various cancers. Naringenin (NAR), a natural flavonoid, protect against CIS-induced injury in rats without hampering CIS beneficial cytotoxic activity. Even though NAR exhibits therapeutic potency, clinical evolution of the molecule is embarrassed because of very less aqueous solubility which corresponds to low availability at the site of the tumor. In our former analysis, nanosuspension of naringenin (NARNS) was developed by the method of high-pressure homogenization. The study had been continued to evaluate the protective role of D-α-Tocopheryl polyethylene glycol succinate (TPGS) coated NARNS, against oxidative stress-induced hepato and nephrotoxicity in male Wistar rats upon CIS treatment. Induction of acute hepato and neprotoxicity was done by intraperitoneal injection (i.p) injection of CIS (7 mg/kg of body weight) and administration of NAR and NARNS. Administration of NARNS virtually suppressed CIS-induced and liver injury evidenced by a reduction of lipid peroxidation level, blood urea nitrogen, serum uric acid, creatinine and elevated enzymatic antioxidant activities of superoxide dismutase, catalase, and glutathione peroxidase in rats liver tissue. Histological studies substantiated the biochemical parameters. The study suggests that NARNS has strong hepato and nephroprotective effect compared to NAR.

Quality by design approach for the preparation of fat-soluble vitamins lipid injectable emulsion.

The fat-soluble vitamins lipid injectable emulsion, a parenteral supplement, commonly used for hospitalized patients to meet daily requirements of fat-soluble vitamins. This study attempts to reduce risk, improve the stability and safety of fat-soluble vitamins lipid injectable emulsion using a Quality by Design (QbD) approach. The quality target product profile and critical quality attributes were defined based on a comprehensive understanding of fat-soluble vitamins lipid injectable emulsions. The emulsions were prepared using a high-pressure homogenization method. Critical quality attributes (CQAs) were identified using risk assessment tools such as fishbone diagram and risk estimation matrix. The assay, mean droplet size, polydispersity index, zeta potential, and the volume-weighted percentage of fat greater than 5 μm (PFAT5) were identified as CQAs. Accordingly, three critical formulation and process parameters for the emulsions were the percentage of emulsifier, homogenization pressure, and homogenization recirculation. The design space was obtained via a design of experiment (DoE), and an optimum formulation was successfully prepared. All physicochemical attributes of the optimal formulation were within the design space (i.e., droplet size: 217.2 ± 0.37 nm; polydispersity index: 0.115 ± 0.012; PFAT5: less than 0.05%; zeta potential: -34.6 ± 1.09 mV; and viscosity: 20.95 mPa at 0.1 s-1). The optimal formulation remained acceptable physicochemical stability at 25 ± 2 °C/60% RH ± 5% RH over a 12-month period. Safety of the optimal emulsion was evaluated as acceptable through the determination of lysophospholipid content and an in vitro hemolysis assay. In conclusion, an optimal lipid injectable emulsion for fat-soluble vitamins was successfully prepared using a QbD approach.

Pickering emulsion stabilization by using amphiphilic cellulose nanofibrils prepared by aqueous counter collision

Cellulose nanofibrils prepared by aqueous counter collision (ACC-nanocelluloses) have specific properties. In this study, the use of ACC-nanocelluloses as emulsifiers and stabilizers was investigated. Oil-in-water Pickering emulsions with long-term stabilities were easily prepared by ultrasonically mixing aqueous ACC-nanocellulose dispersions with non-polar solvents. Stable Pickering emulsions were obtained because the emulsification abilities of the ACC-nanocelluloses were significantly higher than those of cellulose nanofibrils prepared by high-pressure homogenization or other chemical preparation methods. This might be due to exposure of inherently hydrophobic surface planes of cellulose nanofibrils by ACC. The emulsification and stability of the Pickering emulsions were sensitive to the solvent properties such as permittivity, density and viscosity.

Protective effect of sucupira oil nanoemulsion against oxidative stress in UVA-irradiated HaCaT cells.

Bioactive molecules derived from natural products combine the ability to absorb UV light and act as antioxidants. We developed an oil-based sucupira (native species of the Brazilian cerrado) nanoemulsion (NE) using a high-energy emulsification method and assessed its effectiveness in vitro. An easily scalable high-pressure homogenization method was used to prepare the formulation. NE droplets mean diameter, pH, stability, conductivity and morphology were analysed. Formulation bioactivity was assessed using HaCaT cells. The formulation presented suitable pH and size for topic administration and was stable for over 90days upon storage at 4, 25 and 45°C. The NE showed protective effect against oxidative stress and reduced levels of UVA-induced pro-inflammatory cytokines IL-6 and IL-8. A novel, stable and easily prepared formulation was obtained for encapsulation of sucupira oil. The protective effect of the formulation by cytokine inhibition in the early stage of the inflammatory process was shown in vitro. Combined with the antioxidant effect by inhibition of reactive oxygen species, the use of sucupira oil NE for prevention and treatment of UVA-induced stress could contribute to decrease the effects of UV radiation on skin ageing.

Nanostructured lipid carriers containing ondansetron hydrochloride by cold high-pressure homogenization method: Preparation, characterization, and pharmacokinetic evaluation

Nanostructured lipid carriers (NLCs) loaded with ondansetron hydrochloride, a water-soluble drug, were developed for sustained-release delivery. A modified cold high-pressure homogenization method was used, and the pH-dependent solubility of the drug was exploited to obtain NLCs with an enhanced entrapment efficiency. The conditions for cold high-pressure homogenization were optimized at 500 bars for 6 cycles. The pH of the aqueous phase was 7.4, which led to an improvement of the entrapment efficiency to approximately 90%. Certain variables of the formulation composition were evaluated for their influences on ondansetron hydrochloride-loaded NLCs. The transformation of the drug to an amorphous state in NLCs was indicated by differential scanning calorimetry and X-ray powder diffraction. The optimized formulation consisted of tristearin: Phosal® 53MCT: drug (60:40:15, w/w) with 0.5% Tween® 80 (w/v). This formulation exhibited a sustained-release characteristic of the drug in vitro. After single subcutaneous injections in rats, the optimized ondansetron hydrochloride-loaded NLCs prolonged the drug release for up to 96 h with an extended mean resident time and enhanced systemic exposure compared to the drug solution. The developed NLCs might be an efficient approach to prolong the therapeutic effect of ondansetron hydrochloride for the management of chemotherapy- and radiotherapy-induced emesis.

Correction to Erythrocyte Membrane-Camouflaged IR780 and DTX Coloading Polymeric Nanoparticles for Imaging-Guided Cancer Photo-Chemo Combination Therapy.

Conventional systemic chemotherapy leads to poor therapeutic outcomes at moments in cancer therapy because the nontargeting anticancer drug release results in adverse effects and consequently drug resistance. The combination therapeutic strategy provides an alternative way to solve the conundrums. Herein, drug delivery systems with a rational design and tumor-targeting abilities become the ideal carriers for combinatorial therapy. IR780 iodide possesses near-infrared fluorescence intensity for fluorescence imaging (FI) and photothermal conversion for photoacoustic imaging (PAI), which also can be employed for tumor phototherapy (including photothermal therapy and photodynamic therapy). However, hydrophobicity and rapid elimination in vivo limit its biomedical applications. Furthermore, the hydrophobicity and high crystallization of IR780 result in poor drug-loading capacity and low stability. In this study, the high-pressure homogenization method was utilized for hydrophobic molecular IR780 and DTX coloading to construct IR780/DTX-PCEC nanoparticles which exhibit narrow size distribution and satisfactory drug-loading capacity. With further erythrocyte membrane [red blood cell (RBC)] camouflaging, the obtained IR780/DTX-PCEC@RBC nanoparticles present desired stability and prolonged circulation time in vivo. Additionally, the IR780/DTX-PCEC@RBC nanoparticles not only can be employed as a FI/PAI dual model imaging probe but also exhibit the property for phototherapy and chemotherapy of tumors. Based on the therapeutic outcome of combination therapy, the IR780/DTX-PCEC@RBC nanoparticles can serve as promising FI- and PAI-guided photo-chemo combination therapy agents for the future treatment of breast cancer.

Influence of stabilizer type and concentration on the lung deposition and retention of resveratrol nanosuspension-in-microparticles

The purpose of this study was to explore the influence of stabilizer type and concentration on the properties of spray dried nanosuspension-in-microparticles (NS-in-MPs) for inhalation. Taking resveratrol (RES) as a Biopharmaceutical Classification System II (BCS II) model drug, the RES containing nanosuspensions were fabricated by high pressure homogenization method with different stabilizers including sodium dodecyl sulphate (SDS), sodium alginate (SA), chitosan (CS) and polyvinyl alcohol (PVA). Then, the nanosuspensions were spray dried with mannitol to obtain inhalable NS-in-MPs. The particle size, morphology, drug existing state, in vitro aerodynamic performance, in vitro release behavior, lung retention and pharmacokinetic behaviors were characterized. It was found that the morphology, lung deposition as well as in vitro drug release from the microparticles were significantly influenced by stabilizer type, with 1% PVA as stabilizer presenting the highest fine particle fraction (FPF). Meanwhile, taking PVA as an example, it was found stabilizer concentration could alter morphology and flowability of the microparticles, and the FPF value decreased with the increase of stabilizer concentration. Further drug retention and in vivo pharmacokinetic studies demonstrated that the positively charged stabilizer CS could facilitate drug retention and minimize drug expose to the systemic circulation. In conclusion, the deposition and lung retention behavior of NS-in-MPs could be well tuned by selecting different type or concentration of stabilizers, which could facilitate local lung diseases therapy.

Non-aqueous nanoemulsions as a new strategy for topical application of astaxanthin

The application of astaxanthin is limited by its poor solubility and stability. In the present study, astaxanthin non-aqueous nanoemulsions (ASX-NANE) were developed by high-pressure homogenization method to combine advantages of nanocarriers and non-aqueous emulsions. ASX-NANE had a spherical morphology with a uniformed size distribution and a high entrapment efficiency (98.4 ± 0.3%). The analysis of FTIR indicated that astaxanthin was successfully encapsulated into the lipid core of ASX-NANE. This system was a stable emulsion system over a period of 4 weeks at 25 °C and could protect astaxanthin against degradation. In vitro cell study showed that ASX-NANE had a low toxicity and could protect cells against oxidative stress. In vitro permeation study and skin histological sections revealed the enhanced permeation of astaxanthin and the transformation of stratum corneum with a low systemic absorption and unchanged epidermis. Therefore, non-aqueous nanoemulsions might be an appropriate strategy for the topical application of astaxanthin.

Formulation and Optimization of Itraconazole Loaded Novel Nanostructured Lipid Carrier-based Ocular Controlled Release Formulation.

Background: The low penetration power and the retention time into the intraocular tissue are the main problems that make difficult for most of the drugs for the ocular drug delivery system. This is for those drugs that are having the low or poor solubility and the low permeability. Objective: Nanostructured Lipid Carriers (NLCs) loaded with Itraconazole (ITZ) were formulated with the aim to increase the solubility and enhance the retention time in the intraocular tissue. Methods: The NLCs were prepared by using Pluronic (PF127), stearic acid and oleic acid. Itraconazole loaded Nanostructured lipid carrier were prepared by high-pressure homogenization method and the formulations were prepared and optimized by 3 Level Factorial Design. Results: F6 was selected on the basis of better entrapment efficiency (94.65), optimum particle size (310nm), and percentage cumulative release (68.67%). Scanning electron microscopy revealed spherical Nanostructured lipid carrier in the microemulsion. Nanostructured lipid carrier Irritation test showed the non-irritancy and antifungal activity showed a more inhibition zone as compared to the marketed formulation. Conclusion: Conclusively the optimized Formulation (F6) shows better results for the ocular drug delivery as compared to the marked formulation.

Development of Halobetasol-loaded nanostructured lipid carrier for dermal administration: Optimization, physicochemical and biopharmaceutical behavior, and therapeutic efficacy

Halobetasol propionate (HB) is considered a super potent drug in the group of topical corticosteroids. HB has anti-inflammatory activity, vasoconstriction properties, and due to its high skin penetration, it can cause systemic side effects. To improve its characteristics, enhance topical effectiveness and reduce penetration to systemic circulation, a study to optimize and characterize a HB-loaded lipid nanocarrier (HB-NLC) has been made by high-pressure homogenization method. The formulation is composed by HB, surfactant, glyceryl distearate and capric glycerides. The optimized HB-NLC containing 0.01% of HB and 3% of total lipid shows an average size below 200 nm with a polydispersity index ≪0.2 and an encapsulation efficiency ≫90%. The in vitro and in vivo tests indicate that the HB-NLC is not toxic, is well tolerated and has an anti-inflammatory effect because they decrease the production of Interleukins in keratinocytes and monocytes. HB-NLC is considered an alternative treatment for skin inflammatory disorders.

Nano-Emulsion and Nano-Encapsulation of Fruit Flavor: Review

Nano-emulsion and nano-encapsulation of fruit flavor aim to make flavor stabilization which is generally labile in the form of liquid (emulsion) and powder (encapsulation) preparations. Nanotechnology in food is a technology to reduce food particle size to 20-200 nm which is generally followed by new properties both physical, chemical and sensory. In nano-emulsion products such as transparent color and products stability are characterized by: absence of sedimentation (creaming), unification of two particles (flocculation), unification of particles to enlarge (coalescent) and exchange of internal and external phases (inversion). In nano-encapsulation products flavor stability is maintained by reduced aroma volatility which is bound by the carrier matrix while controlling the release of aroma. The method of forming nano-emulsion uses two approaches, namely high energy such as high-pressure homogenization and ultra-sonication methods, and low energy such as spontaneous emulsification. Making an emulsion is by mixing two different compounds of polarity stabilized by the emulsifier. In the emulsion flavor system for making nano-encapsulation a biopolymer is needed which acts as a core coating. The encapsulation was made by making an emulsion first, then one of the drying techniques was carried out such as spray drying, drum drying and freeze drying. This literature review describes nano-emulsion techniques and nano-encapsulation of fruit flavor

Preparation, characterization and dissolution characteristics of dragon's blood extract nanosuspensions

The single-factor test was used to optimize the high-pressure homogenization method to prepare the phenolic extract nanosuspensions(DBNs). The physicochemical properties of the obtained nanosuspensions were characterized and the cumulative release in vitro was evaluated. The results showed that the drug concentration was 0.5 g·L~(-1), the mass concentrations of PVPK30 and SDS were 0.5 and 0.25 g·L~(-1), respectively, the probe ultrasonic time was 5 min, the homogenization pressure was 900 bar, and the number of homogenization was 2 times. The prepared DBNs had an average particle size of(168.80±0.36) nm, polydispersity index(PDI) of 0.09±0.04, stability index(SI) of 0.85, and DBNs were stable for storage within 30 days. Scanning electron microscopy showed that the particle size of the dragon's blood extract was reduced and the uniformity was improved in the obtained nanosuspensions. X-ray diffraction pattern and differential scanning calorimetry showed that the phenolic extract of dragon's blood was still in an amorphous state after being prepared into nanosuspensions. The results of saturated solubility measurement showed that the solubility of DBNs lyophilized powder reached 6.25 g·L~(-1), while the solubility of DB raw powder was only 28.67 mg·L~(-1). The in vitro dissolution experiments showed that DBNs lyophilized powder accumulated in gastrointestinal fluid for 8 h. The release amount was 90%,the cumulative release of the raw powder in the gastrointestinal fluid for 24 h was less than 1%, and the solubility and dissolution rate of the DBNs lyophilized powder were significantly higher than the DB raw powder. The method is simple in process and convenient in operation, and can successfully prepare uniform and stable nanosuspensions to improve its solubility, and provides a research basis for solving the application limitation of dragon's blood extract.

Superolein Based Intravenous Lipid Emulsion 20% w/w Physicochemical Characterization, Stability and Its Effect on Liver Status

Long chain triglycerides (LCT) from soya oil have been reported to cause hepatic abnormalities among patients receiving parenteral nutrition. A new source for LCT is needed to support current therapy. The aims of this study were to develop a good and stable superolein oil based intravenous lipid emulsion 20% (SoLE), and to determine its effect on liver status of an animal model. The emulsion was prepared using superolein oil and medium chain triglyceride oil (1:1), 1.2 g lecithin and homogenized by high pressure homogenization method. The physical stability study was performed based on real-time, accelerated, force degradation and environmental degradation. Chemical stability was measured based on fatty acids and vitamin E contents, peroxide value and acidity value. As the animal model, three rabbits were administered with 1.5 g/kg SoLE for 5 h and repeated daily for three days. The SoLE was found to have good physicochemical characters: 229.07±1.57 nm of particle size; 0.00% of particle > 5 μm; 342.00±1.00 mOsm/kg of osmolarity; -46.67±4.40 mV of zeta potential; 1.72±0.04 cP of viscosity; 7.83±0.06 of pH; 0.80±0.06 kcal/g calorie; 1.74±0.05 mEqO2/kg of peroxide value; and 0.03±0.01% of acidity value, and excellent physicochemical stabilities for up to six months of storage at various temperatures and conditions. The level of plasma lipid and plasma liver enzymes profiles of the rabbits remained statistically unchanged. This study has successfully developed a stable SoLE 20% and it was found to be safe to the liver of the animal model.

Erythrocyte Membrane-Camouflaged IR780 and DTX Coloading Polymeric Nanoparticles for Imaging-Guided Cancer Photo-Chemo Combination Therapy.

Conventional systemic chemotherapy leads to poor therapeutic outcomes at moments in cancer therapy because the nontargeting anticancer drug release results in adverse effects and consequently drug resistance. The combination therapeutic strategy provides an alternative way to solve the conundrums. Herein, drug delivery systems with a rational design and tumor-targeting abilities become the ideal carriers for combinatorial therapy. IR780 iodide possesses near-infrared fluorescence intensity for fluorescence imaging (FI) and photothermal conversion for photoacoustic imaging (PAI), which also can be employed for tumor phototherapy (including photothermal therapy and photodynamic therapy). However, hydrophobicity and rapid elimination in vivo limit its biomedical applications. Furthermore, the hydrophobicity and high crystallization of IR780 result in poor drug-loading capacity and low stability. In this study, the high-pressure homogenization method was utilized for hydrophobic molecular IR780 and DTX coloading to construct IR780/DTX-PCEC nanoparticles which exhibit narrow size distribution and satisfactory drug-loading capacity. With further erythrocyte membrane [red blood cell (RBC)] camouflaging, the obtained IR780/DTX-PCEC@RBC nanoparticles present desired stability and prolonged circulation time in vivo. Additionally, the IR780/DTX-PCEC@RBC nanoparticles not only can be employed as a FI/PAI dual model imaging probe but also exhibit the property for phototherapy and chemotherapy of tumors. Based on the therapeutic outcome of combination therapy, the IR780/DTX-PCEC@RBC nanoparticles can serve as promising FI- and PAI-guided photo-chemo combination therapy agents for the future treatment of breast cancer.