An Overview On Aquasomes : A Novel Approach For Delivering Macromolecules

In recent blossoming era of research in nanobiotechnology, aquasomes are viewed as an effective and efficient carrier system for drug delivery or biochemically active long chain macromolecules like protein and peptide, different hormones, antigens, enzymes and gene delivery. Aquatones are spherical in shape and having particle size within 60- 300nm. Self-assembled structure of aquasome (due to its natural property) it generates a focus on nanobiotechnology research as a carrier system. Mainly, aquasomes contain three-layers, that is core material, coating material, drug layer attached by ionic or non-covalent bond. Aquasomes include mainly the core materials like , hydroxyapatite, solid phase nanocrystalline ceramic diamond (carbon) and calcium phosphate dihydrate(brushite) . The coating of core material is done with glassy polyhydroxyl oligomeric film such as cellobiose and trehalose, on which modification of biochemically active molecules are attached. Whereas, calcium phosphate used as a core material, because of it is naturally present in the body.Whether calcium phosphate is unstable in nature, due to prolong storage it converts into hydroxyapatite which is a better core than calcium phosphate to develop the aquasomes. The solid core material renders stability of structures, while the coating material stabilizes the biochemically active molecules and protects against dehydration. In this review, we tried to an overview of aquasomes, and about its advantages over conventional drug delivery system, shielding effect of aquasomes on desired drug and how its self-assembled structures, makes them an attractive carrier to deliver biochemically active molecules.

Preparation of curcumin nanocrystalline injection and evaluation of its in vivo and in vitro properties / 中国药科大学学报

@#In this study, the formulation and preparation process of curcumin nanocrystalline injection were optimized to improve curcumin dissolution rate and bioavailability in vivo.Media grinding method was used to prepare curcumin nanocrystals, and the particle size was used as the evaluation index.The Box-Behnken experimental design was used to optimize its formulation and preparation process, and to characterize its physical and chemical properties.In addition, the dissolution of nanocrystal with different particle sizes was investigated by the paddle method, and the pharmacokinetics in rats were studied.The experimental results showed that the optimal formula and process were obtained through Box-Behnken experimental design, and that uniform curcumin nanocrystals with an average particle size of 223.1 nm were obtained.The results of X-ray diffraction and differential scanning calorimetry analysis showed that the crystal form was stable during the preparation of nanocrystals. In vitro dissolution experiments with different particle sizes showed that the dissolution rate and the degree of dissolution would increase if the particle size was smaller.Pharmacokinetic studies in rats showed that cmax and AUC0-∞ of curcumin nanocrystal injection were 4.9 and 4.1 times that of curcumin raw materials, respectively.In summary, the curcumin nanocrystal injection developed in this research have a stable preparation process and can significantly improve the dissolution rate and bioavailability of the drug, which provides some ideas for the research on curcumin preparation.

Preparation and in vitro and in vivo evaluation of oral curcumin nanocrystalline capsules / 中国药科大学学报

@#The poorly water-soluble drug curcumin was prepared into oral nanocrystalline solid preparation by nanocrystal technology to improve the solubility, dissolution rate, and bioavailability. Curcumin nanocrystals were prepared by media grinding technology, and two types of stable curcumin nanocrystal suspension formulations were developed. The stabilizers in the two formulations were polyvinylpyrrolidone (PVP K30)/sodium lauryl sulfate (SDS)(1∶1) and Tween 80, respectively. The prepared curcumin nanocrystal suspension was loaded onto microcrystalline cellulose pellets through fluidized bed coating technology, and the nanocrystalline capsules were obtained after filling. The results of nanocrystal redispersion stability and scanning electron microscope (SEM) showed that the morphology of drug-loaded pellets was uniform when PVP K30 and SDS were used as stabilizers, and the diameter of nanocrystals before and after redispersion was about 200 nm, which was determined as the optimal formulation. In vitro dissolution study showed that curcumin nanocrystals at the size of 200 nm exhibited significantly promoted dissolution. The results of X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) showed that the curcumin crystalline partly turned amorphous during the preparation of nanocrystals.Pharmacokinetic studies in rats showed that the bioavailability of curcumin nanocrystals was 9.3 times higher than that of the bulk drug. The curcumin nanocrystalline capsules developed in this research can significantly improve the dissolution rate and bioavailability, which is of great significance in improving the poor solubility of drugs, and is expected to become a new dosage form for clinical treatment.

Micro and nanocrystalline cellulose based oral dispersible film; preparation and evaluation of in vitro/in vivo rapid release studies for donepezil

Oral fast-dispersible film was prepared by utlizing donepezil hydrochloride (drug) and various cellulose derivatives such as hydroxypropyl methyl cellulose (hypermellose) (HPMC), microcrystalline cellulose (MCC) and nanocrystalline cellulose (NCC) to treat Alzheimer's disease. NCC was synthesized by ultra-sonication method using MCC and this was converted to thinfilm formulation (NCC-F) using solvent casting technique. The interaction between the polymer and the drug was investigated by spectral analysis such as UV, FTIR, and 1H- NMR. FTIR confirmed that the compatibility of drug and polymer in ODF formulation. NCC-F has shown an average surface roughness of 77.04 nm from AFM and the average particle size of 300 nm from SEM analysis. Nano sized particle of NCC-F leads faster in vitro dissolution rate (94.53%) when compared with MCC-F and F3 formulation. Animal model (in vivo) studies of NCC-F formulation has reached peak plasma concentration (Cmax) up to 19.018 ng/mL in the span of (tmax) 4 h with greater relative bioavailability of 143.1%. These results suggested that high surface roughness with nanosized NCC-F formulation attained extended drug availability up to (t1/2) 70 h.

Intestinal absorption of puerarin nanocrystalline self-stabilizing pickering emulsion in rats / 中国中药杂志

To study the intestinal absorption characteristics of drug's nanocrystalline self-stabilizing Pickering emulsion (NSSPE) in situ in rats. Rat single-pass intestinal perfusion model was established, and high performance liquid chromatography (HPLC) was used to detect the concentration of puerarin in rat intestinal perfusion solution, assay the absorption rate constant (Ka) and the intestinal apparent permeability coefficient (Papp) of NSSPE in duodenum, jejunum, ileum, and colon, which were compared with those of raw material, nanocrystal and normal emulsion, respectively. For NSSPE, the Ka and Papp values were in the following order: duodenum>jejunum>ileum (<0.05)>colon (<0.01). However, there was no obvious difference between jejunum and ileum. As compared with raw material, nanocrystal and normal emulsion, the Ka and Papp values of NSSPE in duodenum were significantly higher than those of other three preparations (<0.05); and the Ka and Papp values of NSSPE in jejunum and colon were significantly higher than those of raw material, nanocrystal and normal emulsion (<0.01); and the Ka and Papp of NSSPE in ileum were also higher than those of raw material and normal emulsion (<0.05), but had no obvious difference with nanocrystal. The results showed that NSSPE could significantly improve the absorption of puerarin in the intestine of rats.

Effects of drug-oil properties on fabrication of drug nanocrystalline self-stabilizied Pickering emulsions / 中国中药杂志

To investigate the effects of drug and oil properties on the formation and stability of drug nanocrystalline self-stabilizied Pickering emulsions (NSSPE). Three insoluble Chinese medicine components (puerarin, tanshinone ⅡA and ferulic acid) were selected as model drugs, and Capmul C8, Fabrafil M 1944 CS, isopropyl myristate, Pzechwan Lovage Rhizome oil, and olive oil were used as oil phase. NSSPEs were developed by high pressure homogenization method and were evaluated for their appearance, centrifugal stability, droplet size and drug content changes in emulsion layer after storing at room temperature for 14 d. Then the properties of the oil (surface tension and viscosity) and properties of the drugs (surface energy, oil-water partition coefficient, size and Zeta potential of nanocrystalline and drug-water-oil contact angle) on the formation and stability of NSSPE were analyzed. The emulsification property and stability of five samples prepared with ferulic acid nanocrystals and different oils were significantly lower than those of puerarin and tanshinone ⅡA; the particle size of ferulic acid nanocrystals was 3.90 μm, extremely higher than 305 nm of puerarin and 406 nm of tanshinone ⅡA (P<0.05); the zeta potential of ferulic acid nanocrystals was -0.018 0 mV, significantly lower than －29.1 mV of puerarin and -42.6 mV of tanshinone ⅡA (P<0.05). Three samples prepared with isopropyl myristate and different drugs were not emulsions and the viscosity of isopropyl myristate was 4.67 mPa•s, significantly lower than that of the other oils (P<0.01). Puerarin-NSSPEs prepared with Pzechwan Lovage Rhizome oil showed best emulsification property and stability; the contact angle of puerarin in Pzechwan Lovage Rhizome oil-water was 69.7°, close to 90°, significantly higher than other contact angles. NSSPEs made by tanshinone ⅡA-Capmul C8-water, tanshinone ⅡA-Labrafil M 1944 CS-water showed highest stability, with a contact angle of 99.2° and 112° respectively, more close to 90° than other oils. The results indicated that viscosity, size and Zeta potential of nanocrystalline and three-phase contact angle had great influence on the formation and stability of NSSPE; surface tension of oil, surface energy of drug and oil-water partition coefficient may not be related to the construction of NSSPE.

Stability optimization of puerarin nanocrystalline self-stabilizied Pickering emulsion by response surface methodology / 中国中药杂志

A new Pickering emulsion, puerarin nanocrystalline self-stabilized Pickering emulsion (Pu-NSSPE) was developed. Box-Behnken design was used for optimizing the preparation formulation of Pu-NSSPE to improve its stability, and the effects of concentration of puerarin, volume ratio of water to oil, and pH value of water phase on the stratification index of emulsion, droplet size and drug concentration in emulsion were investigated. Results showed that the optimized Pu-NSSPE could be prepared with the concentration of puerarin of 0.5%, the volume ratio of water to oil of 9∶1 and the pH of water of 9. The size of emulsion droplet of optimized Pu-NSSPE was (12.70±1.17) μm and the drug content was (4.49±0.21) g•L⁻¹. The above indexes had no significant changes within the storage of 6 months at room temperature, indicating good stability. Microstructure characterizations by scanning electron micrograph, confocal laser scanning microscope and fluorescence microscope showed that the optimized Pu-NSSPE had a stable core-shell structure of emulsion droplet formed by the adsorption of puerarin nanocrystallines at the surface of oil droplets, which may be the microstructure reason for the long stability of Pu-NSSPE.

Study on feasibility of puerarin nanocrystalline self-stabilizied Pickering emulsion / 中草药

Objective: To investigate the feasibility of Pickering emulsion stabilized by puerarin nanocrystalline. Methods: The new puerarin nanocrystalline self-stabilized Pickering emulsion (Pu-NSSPE) has been developed using the high pressure homogenization method. The influences of drug addition sequence, property, and construction of oil phase, drug concentration, oil/water ratio, homogenization pressure, and pH value of water phase on the formation and stability of Pu-NSSPE were investigated to optimize the preparation technology of Pu-NSSPE. Results: The stability and structure of optimized Pu-NSSPE were studied. It was difficult to form stable Pu-NSSPE if puerarin was first added into water during preparation. The three-phase contact angle and pH value of water phase were key factors for the formation and stability of Pu-NSSPE. Pickering emulsion could be stabilized by puerarin nanocrystalline only when three-phase contact angle of puerarin approaches 90° and water phase was alkaline. When the drug concentration was between 1.0-5.0 mg/mL, stable Pu-NSSPE could be formed. The higher oil/water ratio was, the more oil creamed from Pu-NSSPE was. Low homogenization pressure (below 80 MPa) could not form stable Pu-NSSPE. The size of emulsion droplet of optimized Pu-NSSPE was (10.66 ± 4.81) μm, and drug content was 4.28 mg/mL. The appearance, morphology, and size of emulsion droplets, Zeta potential and drug content were not changed significantly after storage for six months at room temperature. The adsorption of puerarin at the surface of oil droplets was observed by fluorescence microscope. Conclusion: Nanocrystalline of puerarin could stabilize Pickering emulsions, which will provide a promising drug delivery system for puerarin.

Preparation of poorly soluble drug curcumin nanocrystalline self-stabilized Pickering emulsion / 中草药

Objective: To prepare curcumin nanocrystalline (Cur-NC) self-stabilized Pickering emulsion (Cur-NCSPE). Methods: Cur-NCSPE was prepared by high pressure homogenization. The influences of homogenization pressure on Cur-NC size and drug content on Cur-NCSPE formation were studied. The morphology and structure of emulsion droplets were observed by optical microscope and scanning electron microscope. Furthermore, the stability and in vitro release properties of Cur-NCSPE were evaluated. Results: The particle size of Cur-NC was slightly changed when homogeneous pressure was greater than 100 MPa. With the increase of Cur, the amount of Cur-NC on the surface of oil droplets increases, and the particle size decreases. When the amount of drug added can completely cover the surface of oil droplets, increasing the amount of drug had little effect on the particle size. Cur-NCSPE was more stable than Cur-NC and Cur, and the in vitro release rate of Cur-NCSPE was significantly higher than that of Cur-NC and Cur coarse power. Conclusion: The Cur-NCSPE is prepared successfully, which is expected to provide a novel oral administration technology platform for the poorly soluble drugs.

Preparation and evaluation of silybin nanocrystallines self-stabilizing Pickering emulsion / 药学学报

A new silybin nanocrystallines self-stabilizing Pickering emulsion (SN-SSPE) was developed using the high pressure homogenization method to improve the oral bioavailability of silybin. The influences of homogenization pressure from 50 to 120 MPa and drug content from 100 mg to 1000 mg on the formation of SN-SSPE were studied. The morphology, structure and size of emulsion droplet in SN-SSPE were characterized using scanning electron micrograph and confocal laser scanning microscope. SN-SSPE was evaluated, including stability, in vitro release and in vivo oral bioavailability. The particle size of silybin nanocrystallines (SN-NC) was decreased as the pressure increased until 100 MPa. When the drug content reached 300 mg or above, stable SN-SSPE was formed from sufficient SN-NC covering surfaces of oil droplets completely. The emulsion droplet of SN-SSPE with the size of 27.3±3.1 μm showed a core-shell structure consisting of oil droplet as core and SN-NC as shell. SN-SSPE showed a high stability over 40 days. In vitro release rate of SN-SSPE was faster than silybin coarse powder and similar to silybin nanocrystallines suspension (SN-NCS). After intragastric administration in rats, the peak concentration of SN-SSPE was increased by 2.5-fold and 2.3-fold compared with SN-NCS and silybin coarse powder, respectively. The AUC of SN-SSPE was increased by 1.4-fold and 3.8-fold compared with SN-NCS and silybin coarse powder, respectively. All these results showed that nanocrystallines of the poorly soluble drug could stabilize Pickering emulsions, which provides a promising application to the improvement of the oral bioavailability of poorly soluble drugs.

Platelet Rich Fibrin and Nanocry stalline Hydroxyapatite with Collagen Combination in Treatment of Periapical Lesion: A Novel Clinical Approach.

Aims: To use platelet rich fibrin (PRF), which is an autologous platelet concentrate, along with nanocrystalline hydroxyapatite with collagen for treatment of periapical lesion and negotiation of calcified canal of adjacent tooth. Case Presentation: A 19-year-old female reported to the Department of Conservative Dentistry and Endodontics with chief complaint of pain in maxillary right central incisor. Past dental history revealed trauma which she sustained 10 yrs back in the same region. On intraoral examination, there was a draining sinus, in relation to the apex of 11. Also discolouration and crown fracture was found in relation to 11. Periapical radiograph revealed a large diffused periapical radiolucency in relation to 11 and 12, open apex of 11 and calcified root canal in relation to 12. Technique Used in the Study: A periapical surgery under local anaesthesia was planned in the region of maxillary right anterior region in relation to tooth no 11 and 12. Before surgery calcified canal of tooth no 12 was negotiated. PRF and nanocrystalline hydroxyapatite with collagen combination were placed in bony cavity. Follow up of the case was done for period of 6 months. Discussion: In present case combination of nanocrystalline hydroxyapatite with collagen and PRF is used, as it helps in faster bone regeneration. Graft material is osteoconductive and collagen network provides a better scaffold for clot formation and bone regeneration. Conclusion: The combination of PRF and nanocrystalline hydroxyapatite with collagen has been demonstrated to be an effective approach to induce faster periapical healing in present case with large periapical lesion.

Research on Gas-Sensing Properties of TiO2-SnO2 Composite Nanocrystalline to Ozone under Ultra-Violet Light / 分析化学

TiO2-SnO2 composite nanocrystalline was prepared by the low temperature hydrothermal method. A new film-type ozone sensor was developed by using TiO2-SnO2 composite nanocrystallines transferred onto an alumina ceramic tube with Au electrodes by dip-coating method. The crystalline phase and microstructure of TiO2-SnO2 nanocrystallines were characterized by X-ray diffraction ( XRD) , field emission scanning electron microscope ( FE-SEM) , energy dispersive X-ray analysis ( EDAX) and ultraviolet-visible spectrometry ( UV-Vis) . The ozone sensitive mechanism and photoelectrochemical properties of TiO2-SnO2 nanocrystallines were analyzed by using ultraviolet-visible spectrometry and electrochemical method. These characteristic tests of ozone sensor were carried out on the traits of sensitive performance, dynamic response, interference and stability under ultraviolet-visible illumination by the XEDWS-60 A type multifunction analyzer in gas sensor static test system. the conclusion demonstrates that when the ozone sensor based on TiO2-SnO2 composite nanocrystalline ( molar ratio of Ti and Sn is 6 ) was under conditions of 40% relative humidity and 25 ℃operating temperature, when ozone concentration was increased from 0. 1 to 1. 8 μg/L, the best linearity of ozone sensor upon ultraviolet illumination and visible illumination were 97 . 5% and 78 . 5%, the dynamic response time was 2 s and 9 s, the recovery time was 5. 5 s and 15 s. This kind of sensor showed good anti-disturbance to the gases, such as CO, NOx , formaldehyde, acetone, butanol and methanol. The response value of ozone sensor was attenuated about 4 . 7%, when ozone sensor was applied continually on the automobile about 12 months, and its normal time was 8. 5 months.

The Effectiveness of Home Treatment with Nanocrystalline Silver Product (Acticoat(TM)) on the Chronic Ulcerative Lesion of Foot / 대한족부족관절학회지

PURPOSE: This study was performed to evaluate the effectiveness of self-home dressing with nanocrystalline silver dressing method on the treatment of chronic ulcer wounds of the foot. MATERIAL AND METHODS: One hundred-nine patients with chronic foot ulcer due to various causes were treated with nanocrystalline silver dressing material. Dressing was done by themselves in their home. Dressing changes were performed every 2 to 3 days until complete reepithelization. RESULTS: One hundred two cases of all cases had a complete reepithelization. It took 49 days to have a complete reepithelization on average. Seven cases failed to complete reepithelization because of infection. There was no silver intoxication in any cases. CONCLUSION: Using nanocrystalline silver is a useful dressing method for various superficial chronic ulcer and it can be done by themselves at their home. Thus it is considered to be more comfortable to both patients and doctors.

Treatment for Hydrofluoric Acid Chemical Burn Using Acticoat(R)

PURPOSE: Hydrofluoric acid(HF) is one of the most dangerous mineral acids with the dissociated fluoride ions. The initial corrosive burn is caused by free hydrogen ion, and the second and more severe burn is caused by penetration of fluoride ions into subcutaneous tissues. Silver is a cation producing dressing, an effective antimicrobial agent, but older silver-containing formulations are rapidly inactivated by wound environment, requiring frequent replenishment. But, Acticoat(R) is a relatively new form of silver dressing which helps avoid the problems of earlier agents. The aim of this study is to evaluate effects of Acticoat(R), silver-containing dressing on the treatment for HF injury wound. METHODS: From september 2006 to september 2007, the study was carried out with 10 patients who had HF partial thickness burns. Acticoat(R) dressing and 10% calcium gluconate wet gauze dressings in 10 cases. As a principle, in the emergency treatment, partial or complete removal of the nail and early bullectomy along with copious washing with normal saline was done, depending on the degree of HF invasion of the wound. Wound was dressed with Acticoat(R) and 10% calcium gluconate solution. The effect of dressing was investgated by serial bacterial culture and wound exudates assessment. RESULTS: We therefore reviewed 10 cases of HF- induced chemical burns and treatment principle. The 10 cases who came to the hospital nearly immediately after the injury healed completely without sequelae. CONCLUSION: As the industrial sector develops, the use of HF is increasing more and more, leading to increased incidences of HF-induced chemical burns. The education of patients regarding this subject should be empathized accordingly. In conclusion, Acticoat(R) dressing is a better choice for HF partial thickness burn injuries because of shorter healing time, less pain and more comfortable dressing.

The Effectiveness of a Dressing Method using Nanocrystalline Silver for Chronic Wounds / 대한피부과학회지

BACKGROUND: The successful management of chronic wounds requires adequate dressing materials and methods. Nanocrystalline silver is a recently developed form of silver antimicrobial barrier dressing material which has rapid and sustained anti-bacterial activity, reduces inflammation and promotes wound healing. OBJECTIVE: This study was done to evaluate the effect of nanocrystalline silver dressing method on the treatment of chronic wounds. METHODS: Twenty three patients with chronic wounds of various etiologies were treated with nanocrytalline silver mesh dressing material (Acticoat(TM)) using an occlusive method. Dressing changes were performed every 2 to 3 days until reepithelization. RESULTS: The treatment with nanocrystalline silver was effective in 21 of 23 cases. This dressing method can significantly reduce the frequency of dressing changes, and thus it was more comfortable to both patients and doctors. CONCLUSION: Occlusive method using nanocrystalline silver is a useful dressing method for various chronic wounds, particularly in an outpatient setting.

Effectiveness of Nanocrystalline Silver(Acticoat(R) Dressing at Wound Infected by Multidrug Resistant Bacteria

PURPOSE: The emergency of multi-drug resistant stains of bacteria represents a challenge in the field of plastic surgery. Especially, MRSA(methicillin-resistant Staphylococcus aureus) and Pseudomonas aeruginosa have strong pathogenicity as well as multi-drug resistance so that they have become a lot more problematic strains. This study has been planned to reduce the bacterial burden by applying Acticoat(R)(Smith & Nephew Healthcare, Hull, England)?dressing into the chronic wounds infected by multi-drug resistant strains and to facilitate their healing. METHODS: Nanocrystalline silver dressings(Acticoat(R)) were applied to chronic wound infected by MRSA or Pseudomonas aeruginosa. Multi-drug resistant bacteria were smeared over a slide glass using sterilized cotton swabs and gram stains were performed directly before and after applying Acticoat(R) dressings at 1, 24, 48 and 72 hours. The gram-stained slides were observed using an optical microscope magnified 1000 times(x1000). The bacterial counts of the control group(0 hour) were compared to those of the experimental groups(1, 24, 48, and 72 hour). Paired T-test was used to assess a statistical significance. MRSA was cultured in two BAPs(blood agar plate) and two MacConkey plates with streak plate method. None were interventions on one culture plate, while on the other culture plate, Acticoat(R) was placed in a square shape and cultured for 72 hours at 37 degrees C, then plates were examined. Pseudomonas aeruginosa was cultured in the same manner as MRSA. RESULTS: There are the large amount of declination of bacterial counts with statistical significance after Acticoat(R) dressing. The bacteria grew in culture plate without specific intervention, but no bacteria grew in culture plate with applying of Acticoat(R) dressing. CONCLUSION: We believe that Acticoat(R) dressing could be used as an effective method of treating chronic wounds which are infected by multi-drug resistant organisms.

Antimicrobial Effects of Nano-Silver Gauze against Common Bacterial Isolates / 병원감염관리

BACKGROUND: Silver has been used for disinfection and sterilization. We aimed to confirm the in-vitro antibacterial effects of nanocrystalline silver-coated gauze. METHODS: Fourteen clinical isolates each of Escherichia coli and Acinetobacter baumannii were used. Bacterial suspensions made in tryptic soy broth were exposed to Ordinary and silver-coated gauze. Bacteria were then harvested from the gauze immediately and after 24 h incubation, cultured on blood agar plates and eunmerated for viable counts. The number of colonies was converted into common logarithms for comparison. RESULTS: The number of colonies recovered from silver-coated gauze was significantly lower than those recovered from ordinary gauze when harvested immediately after exposure (E. coli, 3.06 vs 1.73; A. baumannii, 3.13 vs 1.98; P<0.001). After 24 h incubation of exposed gauze, silver-coated gauze produced less than 1 CFU/mL, whereas ordinary gauze produced a number of colonies significantly higher than it did immediately after exposure (E. coli, 4.13; A. baumannii, 4.46; P<0.001). Conclusion: Compared with ordinary gauze, silver-coated gauze was shown to have 99.99% antibacterial effect.