Intradermal and follicular delivery of adapalene liposomes

Abstract

Background: Adapalene is a widely used topical anti-acne drug; however, it has many side effects. Liposomal drug delivery can play a major role by targeting delivery to pilosebaceous units, reducing side effects and offering better patient compliance.

Objective: To prepare and evaluate adapalene-encapsulated liposomes for their physiochemical and skin permeation properties.

Methods: A liposomal formulation of adapalene was prepared by the film hydration method and characterized for shape, size, polydispersity index (PDI), encapsulation efficiency and thermal behavior by techniques such as Zetasizer®, differential scanning calorimetry and transmission electron microscopy. Stability of the liposomes was evaluated for three months at different storage conditions. In vitro skin permeation studies and confocal laser microscopy were performed to evaluate adapalene permeation in pig ear skin and hair follicles.

Results: The optimized process and formulation parameters resulted in homogeneous population of liposomes with a diameter of 86.66?±?3.5?nm in diameter and encapsulation efficiency of 97.01?±?1.84% w/w. In vitro permeation studies indicated liposomal formulation delivered more drug (6.72?±?0.83?μg/cm²) in hair follicles than gel (3.33?±?0.26?μg/cm²) and drug solution (1.62?±?0.054?μg/cm²). Drug concentration delivered to the skin layers was also enhanced compared to other two formulations. Confocal microscopy images confirmed drug penetration in the hair follicles when delivered using the liposomal formulation.

Conclusion: Adapalene was efficiently encapsulated in liposomes and led to enhanced delivery in hair follicles, the desired target site for acne.     

Preparation and evaluation of optimized zolmitriptan niosomal emulgel

Objective: Novel niosomal formulation may be successfully applied to treat a systemic disease such as migraine through transdermal drug delivery system (TDDS), moreover, the treatment of topical diseases such as mycotic infections by targeting and localizing the drug to the stratum corneum. The current study aims to formulate zolmitriptan (Zt) in niosomal vesicles to potentiate its transdermal effect.

Significance: The development of a promising niosomal formulation will push the scaling up of pharmaceutical industry in this field.

Methods: Design- Expert 10 was used to design twelve formulations using Box-Behnken. Zt loaded niosomes were prepared by the thin film hydration method using Span 60(S 60), Span 80(S 80) along with cholesterol(Ch) at three different levels. The optimized formulation (F11) was formulated in Emulgel (1:1 emulsion/gel ratio).

Results: The vesicles revealed vesicle size (VS) ranging from 133.1 to 851.3?nm, zeta potential (ZP) ?43.8 to ?82.8?mV, entrapment efficiency (EE%) from 66.7 to 88.7%, and Zt release after 4?h up to 67%. Optimized niosomal formulation (F11) depicted the smallest VS (133.1?nm), highest EE (88.7%), high ZP (?80.6?mV) and satisfactory release after 4?h (61.5%). There was a significant difference (p <.05) in drug permeation after 8?h for niosomal F11(460.98?ug/cm²) and niosomal F11 loaded Emulgel (336.92?ug/cm²) compared to plain Zt loaded emulgel (160.83?ug/cm²). Niosomal F11 loaded emulgel showed thixotropic behavior of rapid recovery, significant bioavailability and pharmacokinetic parameters as compared to the plain Zt-loaded Emulgel.

Conclusion: Optimized F11 represents a promising formulation for transdermal drug delivery system to treat both topical and systemic diseases.     

Phospholipid–polymer hybrid nanoparticle-mediated transfollicular delivery of quercetin: prospective implement for the treatment of androgenic alopecia

Abstract

Objectives: The aim of the study was to deliver effective doses of quercetin (Que) to the lower region of hair follicles (HFs) using the transfollicular route through dipalmotylphosphatidylcholine (DPPC)-reinforced poly lactide-co- glycolide nanoparticles (DPPC-PLGA hybrid NPs) for the treatment of alopecia.

Method: PLGA and DPPC-PLGA hybrid NPs were prepared by double-emulsification solvent evaporation method. NPs were characterized for size, shape, zeta potential entrapment and drug release. Drug-polymer interactions were determined by infrared spectroscopy (Fourier transform infrared spectroscopy, FTIR) and differential scanning calorimetry (DSC). Follicular uptake of fluorescent marker tagged NPs was assessed on isolated rat skin by fluorescent microscopy. Potential of hybrid NPs to induce hair regrowth was tested on testosterone-induced alopecia in rat models by visual inspection, hair follicular density measurement (no./mm), and histological skin tissue section studies.

Key findings: Hybrid NPs had mean vesicles size 339?±?1.6, zeta potential –32.6?±?0.51, and entrapment efficiency 78?±?5.5. Cumulative drug release after 12?h was found to be 47.27?±?0.79%. FTIR and DSC confirmed that drug was independently dispersed in the amorphous form in the polymer. Data from fluorescence microscopy suggested that NPs were actively taken up by HFs. In-vivo studies on alopecia-induced rat models showed that hybrid NPs improved hair regrowth potential of Que and accumulation of NPs at HFs end region inhibit HFs cells apoptosis.

Conclusion: This study concludes that phospholipid–polymer hybrid NPs could be the promising transfollicular delivery system for Que in the treatment of androgenic alopecia management.     

Formulation design and optimization of novel soft glycerosomes for enhanced topical delivery of celecoxib and cupferron by Box–Behnken statistical design

Background: The present study describes glycerosomes (vesicles composed of phospholipids, glycerol and water) as a novel drug delivery system for topical application of celecoxib (CLX) and cupferron (CUP) compound.

Aim: The goal of this research was to design topical soft innovative vesicles loaded with CLX or CUP for enhancing the efficacy and avoiding systemic toxicity of CLX and CUP.

Methods: CLX and CUP loaded glycerosomes were prepared by hydrating phospholipid-cholesterol films with glycerol aqueous solutions (20–40%, v/v). Box–Behnken design, using Design-Expert® software, was the optimum choice to statistically optimize formulation variables. Three independent variables were evaluated: phospholipid concentration (X₁), glycerol percent (X₂) and tween 80 concentration (X₃). The glycerosomes particle size (Y₁), encapsulation efficiency percent (Y₂: EE %) and drug release (Y₃) were selected as dependent variables. The anti-inflammatory effect of CLX and CUP glycerosomal gel was evaluated by carrageenan-induced rat paw edema method followed by histopathological studies.

Results: The optimized formulations (CLX2* and CUP1*) showed spherical morphology under transmission electron microscopy, optimum particle size of 195.4?±?3.67?nm, 301.2?±?1.75?nm, high EE of 89.66?±?1.73%, 93.56?±?2.87%, high drug release of 47.08?±?3.37%, 37.60?±?1.89% and high cumulative amount of drug permeated in 8?h of 900.18?±?50.24, 527.99?±?34.90?µg.cm^?2 through hairless rat skin, respectively. They also achieved significant remarkable paw edema inhibition in comparison with the control group (p? Conclusion: Finally, the administration of CLX2* and CUP1* loaded glycerosomal gel onto the skin resulted in marked reduction of edema, congestive capillary and inflammatory cells and this approach may be of value in the treatment of different inflammatory disorders.     

Formulation and ex vivo–in vivo evaluation of pH-triggered brimonidine tartrate in situ gel for the glaucoma treatment using application of 32 factorial design

Context: Short residence time, poor bioavailability and poor permeability are the major problems for conventional eye drops treatment.

Objective: The aim of this article is to develop, optimize and ex vivo–in vivo investigation of brimonidine tartrate in situ gel as compared to marketed eye drops for the treatment of glaucoma.

Materials and methods: The effect of independent variables, namely concentrations of polymers, on various dependent variables like viscosity at physiological pH and in vitro drug release were studied by using 3² factorial design. Further the optimized formulation was characterized for ex vivo and in vivo study.

Results and discussion: Experimental data demonstrated that optimized in situ gel formulation (F8) showed in vitro–ex vivo sustained release profile with polymer composites carbopol 974P and HPMC K4M. After 5?h of ex vivo transcorneal permeation study, the amount recovered from the corneal surface on the donor chamber 12.40% (124 ug) and the amount collected from the receptor chamber 76.8% (760 ug) of the initial dose 1?mg. The total amount recovered from the permeation experiment was 89.2%. Bioadhesive carbopol 974P and viscosity HPMC K4M composites optimized formulation (F 8) produce greater influence on the duration of drug action and improved intraocular pressure reduction activity as compared to marketed eye drop solution in in vivo study.

Conclusion: The developed in situ gelling system as a promising ophthalmic formulation to prolong the drug lowering effect on the intraocular pressure.     

Development and characterization of a ricinoleic acid poloxamer gel system for transdermal eyelid delivery

Objective: This study deals with the preparation and evaluation of a pluronic lecithin organogel (PLO gel) containing ricinoleic acid for the transdermal eyelid delivery of dexamethasone and tobramycin.

Methods: Five different PLO gel formulations (F1, F2, F3, F4 and F5) containing tobramycin (0.3%) and dexamethasone (0.1%) were prepared and compared to a conventional PLO gel (light mineral oil PLO gel, F6) with respect to physical appearance and viscosity. The optimized ricinoleic acid PLO gel formulation (F2) was further characterized for pH, gelation temperature, morphology and drug content. Ex vivo permeability of dexamethasone and bactericidal activity of tobramycin from formulation F2 was tested, and values were compared to the marketed Tobradex® eye ointment.

Results: No apparent changes in the physical appearance and consistency were observed when ricinoleic acid was used as the oil phase. The pH of the optimized ricinoleic acid PLO gel (formulation F2) was found to be 6.54 with a gelation temperature of 31?°C. The drug content of tobramycin and dexamethasone were found to be 102.8% and 100.14%, respectively. The penetration profile of dexamethasone from formulation F2 was found to be much higher than the marketed Tobradex® eye ointment. F2 showed a better antimicrobial activity and higher zones of inhibition when compared to the marketed Tobradex® eye ointment.

Conclusion: The findings of this investigation indicate that the ricinoleic acid PLO gel has the potential for use as a transdermal eyelid delivery system.     

Physicochemical characterization of spray-dried PLGA/PEG microspheres,and preliminary assessment of biological response

Context: The use of spray-drying to prepare blended PLGA:PEG microspheres with lower immune detection.

Objective: To study physical properties, polymer miscibility and alveolar macrophage response for blended PLGA:PEG microspheres prepared by a laboratory-scale spray-drying process.

Methods: Microspheres were prepared by spray-drying 0–20% w/w ratios of PLGA 65:35 and PEG 3350 in dichloromethane. Particle size and morphology was studied using scanning electron microscopy. Polymer miscibility and residual solvent levels evaluated by thermal analysis (differential scanning calorimetry – DSC and thermogravimetric analysis – TGA). Immunogenicity was assessed in vitro by response of rat alveolar macrophages (NR8383) by the MTT-based cell viability assay and reactive oxygen species (ROS) detection.

Results: The spray dried particles were spherical, with a size range of about 2–3?µm and a yield of 16–60%. Highest yield was obtained at 1% PEG concentration. Thermal analysis showed a melting peak at 59?°C (enthalpy: 170.61 J/g) and a degradation-onset of 180?°C for PEG 3350. PLGA 65:35 was amorphous, with a T_g of 43?°C. Blended PLGA:PEG microspheres showed a delayed degradation-onset of 280?°C, and PEG enthalpy-loss corresponding to 15% miscibility of PEG in PLGA. NR8383 viability studies and ROS detection upon exposure to these cells suggested that blended PLGA:PEG microspheres containing 1 and 5% PEG are optimal in controling cell proliferation and activation.

Conclusion: This research establishes the feasibility of using a spray-drying process to prepare spherical particles (2–3?µm) of molecularly-blended PLGA 65:35 and PEG 3350. A PEG concentration of 1–5% was optimal to maximize process yield, with minimal potential for immune detection.     

Solidification of hesperidin nanosuspension by spray drying optimized by design of experiment (DoE)

Objective: To accelerate the determination of optimal spray drying parameters, a “Design of Experiment” (DoE) software was applied to produce well redispersible hesperidin nanocrystals.

Significance: For final solid dosage forms, aqueous liquid nanosuspensions need to be solidified, whereas spray drying is a large-scale cost-effective industrial process.

Methods: A nanosuspension with 18% (w/w) of hesperidin stabilized by 1% (w/w) of poloxamer 188 was produced by wet bead milling. The sizes of original and redispersed spray-dried nanosuspensions were determined by laser diffractometry (LD) and photon correlation spectroscopy (PCS) and used as effect parameters. In addition, light microscopy was performed to judge the redispersion quality.

Results: After a two-step design of MODDE 9, screening model and response surface model (RSM), the inlet temperature of spray dryer and the concentration of protectant (polyvinylpyrrolidone, PVP K25) were identified as the most important factors affecting the redispersion of nanocrystals. As predicted in the RSM modeling, when 5% (w/w) of PVP K25 was added in an 18% (w/w) of hesperidin nanosuspension, subsequently spray-dried at an inlet temperature of 100?°C, well redispersed solid nanocrystals with an average particle size of 276?nm were obtained. By the use of PVP K25, the saturation solubility of the redispersed nanocrystals in water was improved to 86.81?µg/ml, about 2.5-fold of the original nanosuspension. In addition, the dissolution velocity was accelerated.

Conclusions: This was attributed to the additional effects of steric stabilization on the nanocrystals and solubilization by the PVP polymer from spray drying.     

Development,optimization, and characterization of a novel tea tree oil nanogel using response surface methodology

Purpose: To develop and optimize nanoemulsion (NE)-based emulgel (EG) formulation as a potential vehicle for topical delivery of tea tree oil (TTO).

Methodology: Central composite design was adopted for optimizing the processing conditions for NE preparation by high energy emulsification method viz. surfactant concentration, co-surfactant concentration, and stirring speed. The optimized NE was developed into emulgel (EG) using pH sensitive polymer Carbopol 940 and triethanolamine as alkalizer. The prepared EG was evaluated for its pH, viscosity, and texture parameters, ex vivo permeation at 37?°C and stability. Antimicrobial evaluation of EG in comparison to conventional gel and pure TTO was also carried out against selected microbial strains.

Results and discussion: Optimized NE had particle size and zeta potential of 16.23?±?0.411?nm and 36.11?±?1.234?mV, respectively. TEM analysis revealed the spherical shape of droplets. The pH of EG (5.57?±?0.05?) was found to be in accordance with the range of human skin pH. EG also illustrated efficient permeation (79.58?μL/cm²) and flux value (J_SS) of 7.96?μL cm²/h through skin in 10?h. Viscosity and texture parameters, firmness (9.3?±?0.08?g), spreadability (2.26?±?0.06?mJ), extrudability (61.6?±?0.05?mJ), and adhesiveness (8.66?±?0.08?g) depict its suitability for topical application. Antimicrobial evaluation of EG with same amount of TTO as conventional gel revealed broader zones of growth inhibitions against all the selected microbial strains. Moreover, EG was also found to be nonirritant (PII 0.0833). These parameters were consistent over 90 d.

Conclusion: TTO EG turned out to be a promising vehicle for the topical delivery of TTO with enhanced therapeutic efficacy.     

Evaluation of the percutaneous absorption of chlorpromazine from PLO gels across porcine ear and human abdominal skin

Objective: The overall objective of this work is to determine the percutaneous absorption of chlorpromazine hydrochloride from pluronic lecithin organogels (PLO gels) and verify the suitability of topically applied chlorpromazine hydrochloride PLO gels for use in hospice patients for relieving symptoms such as vomiting and nausea during the end stages of life.

Methods: PLO gels of chlorpromazine hydrochloride were prepared using isopropyl palmitate (IPP) or ricinoleic acid (RA) as oil phase. In vitro percutaneous absorption of chlorpromazine hydrochloride was assessed through porcine ear and human abdominal skin. Further, the theoretical steady state plasma concentration (C_ss) of chlorpromazine was calculated from the flux values.

Results: The pH, viscosity, and stability of both PLO gels prepared with IPP and RA were comparable. The thixotropic property of RA PLO gel was found to be better than that of IPP PLO gel. The permeation of chlorpromazine hydrochloride was higher from RA PLO gel than from IPP PLO gel and pure drug solution. Theoretical C_ss of chlorpromazine from pure drug solution, IPP PLO gel and RA PLO gel were found to be 1.05, 1.20, and 1.50?ng/ml, respectively. PLO gels only marginally increased the flux and theoretical C_ss of chlorpromazine.

Conclusion: From this study, it is clearly evident that PLO gels fail to achieve required systemic levels of chlorpromazine following topical application. Chlorpromazine PLO gel may not be effective in treating nausea and vomiting for hospice patients with swallowing difficulties.     

Preparation and evaluation of HPMC-based pirfenidone solution in vivo

Abstract

Context: Pirfenidone (PFD) has exhibited therapeutic potential in the treatment of cell proliferative disorders. The previously developed 0.5% water-based PFD eye drops by our team exhibited antiscarring effectiveness and ocular safety but with a limit of short half-life and poor bioavailability.

Objective: To increase bioavailability of the water-based PFD eye drops, we prepared a viscous solution by adding hydroxypropyl methylcellulose (HPMC, F4M), which acted as a viscosity-enhancer. Subsequently, we compared the HPMC-based PFD solution with the water-based PFD eye drops.

Materials and methods: PFD solution with 1% HPMC (w/v) was prepared, and the viscosities at different shear rates were measured to investigate its rheology. PFD concentrations in the tear, aqueous humor, conjunctiva, cornea, and sclerae of New Zealand rabbits were detected at different time points with high-performance liquid chromatography (HPLC) following single instillation of the 0.5% PFD (w/v) water-based eye drops or HPMC-based solution.

Results: Compared with the 0.5% water-based PFD eye drops, the HPMC-based solution increased the PFD levels in tears and prolonged the residence time from 10 to more than 20?min (p?<?.01). Consequently, the concentrations of PFD in aqueous humor, conjunctiva, cornea, and sclera were elevated to varying degrees until 90?min after topical administration.

Conclusions: The developed formulation possesses a same readily administration and simple preparation as the PFD eye drops; however, the HPMC-based solution exhibited the higher bioavailability.     

Natural polysaccharides platforms for oral controlled release of ketoprofen lysine salt

Context: Ketoprofen lysinate (KL) is one of the most widely used non-steroidal anti-inflammatory drugs in the symptomatic treatment of some chronic inflammatory diseases. Compared to ketoprofen, KL shows better pharmacokinetics and tolerability. However, due to its short half-life of 1–2?h, a multiple dose regimen is required for oral administration. Thus, the present work deals with its encapsulation in a hydrogel-based system by prilling in order to prolong its activity.

Objective: In this paper, we propose alginate and pectin as carriers and release tailoring agent for the development of hydrogel-based beads for KL retarded and sustained release.

Materials and methods: Beads were produced by a Nisco Encapsulator® using alginate or pectin. Operative variables were optimized to produce beads with desired morphology and size. Solid state properties were analyzed by SEM and DSC. Drug release performance was studied by Pharmacopeia pH-change assay to simulate gastrointestinal environment.

Results and discussion: Prilling technique was successfully used to encapsulate high soluble drugs as KL in polysaccharides-based hydrogels. Pectin proved to be a proper polymer able to encapsulate ketoprofen lysine salt. Formulation (F8) showed good morphological properties and size, high drug content (15.6%) and encapsulation efficiency (93.5%) and promising drug release profiles. Hosting F8 in an acid-resistant capsule (DR^®caps) a delivery platform has been developed to control KL release in a delayed (90?min lag time) and prolonged way (270?min complete release).

Conclusion: The platform may be proposed as potentially useful in the oral administration of NSAIDs in chronic inflammatory diseases affected by circadian rhythm.     

Topical delivery of paclitaxel for treatment of skin cancer

Context: Skin cancer represents the most growing types of cancer in human and ultraviolet radiation can be cited as one of the prime factor for its occurrence. Current therapy of skin cancer suffers from numerous side effects; for effective therapy, topical application of formulation of paclitaxel (PTX) can be considered as a novel approach.

Objective: The present study is an attempt to prepare formulation of solid lipid nanoparticles (SLN) of PTX for the effective treatment of various form of skin carcinoma.

Methods: The SLN were prepared by high-speed homogenization and ultrasonication method. The prepared SLN were characterized. The optimized PTX SLN were loaded in carbopol gel. The prepared gels were evaluated for its gelling properties and finally studied for in vivo anti-cancer efficacy and histopathological study.

Results: The particle size distribution was found to be in the range of 78.82–587.8?nm. The product yield (%) was found between 60% and 66% and showed a highest entrapment efficiency of 68.3%. The in vitro release of the drug from SLN dispersion was found to be biphasic with the initial burst effect, followed by slow release. SLN-loaded gel were subjected to permeability study and the results show steady-state flux (J_ss), permeability coefficient (K_p), and enhancement ratio were significantly increased in SLN-loaded gel formulation as compared with PTX-loaded gel. The histopathological study clearly reveals the efficacy of the SLN-F3 3G in the treatment of skin cancer.

Conclusion: The experimental formulations show controlled release of PTX and thus expected to show reduce dose-related side effects.     

Enhanced antitumor activity in A431 cells via encapsulation of 20(R)-ginsenoside Rg3 in PLGA nanoparticles

Objective: The objective of this study is to investigate the encapsulation of 20(R)-ginsenoside Rg3 (20(R)-Rg3) using polylactic-co-glycolic acid (PLGA) and promotion for its antitumor activity.

Significance: Preparation and evaluation of the antitumor efficacy of 20(R)-Rg3-loaded PLGA nanoparticles were the first reported. The data will be helpful to apply 20(R)-Rg3 efficiently and broadly in new drug form development and clinical cancer treatment.

Methods: The nanoparticles were prepared using emulsion and solvent evaporation methods. The uniform particle size and good dispersion were further confirmed by scanning electron microscopy. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was applied to detect cell proliferation after 20(R)-Rg3-loaded PLGA nanoparticles treatment. Western blotting and immunofluorescent staining were used for observation of key proteins related with proliferation and apoptosis. Cell cycle and apoptosis were analyzed by flow cytometer technology.

Results and discussion: The results showed that the size of 20(R)-Rg3-loaded PLGA was 97.5?nm in diameter, and zeta potential was ?28?mV detected by Malvern particle size analyzer. The encapsulation efficiency was 97.5%, and drug loading was 70.2% measured by high-performance liquid chromatography. The in vitro study showed that the encapsulated 20(R)-Rg3 was consecutively released and the release ratio reached to the highest value (19.36%) at the time point of 96?h. The encapsulated 20(R)-Rg3 significantly inhibited the proliferation and induced apoptosis in A431 cancer cells compared with the unencapsulated 20(R)-Rg3, control and PLGA alone.

Conclusion: 20(R)-Rg3-loaded PLGA nanoparticles was well prepared and characterized. The antitumor activity was increased after PLGA encapsulation. The data will be beneficial to the development of new dosage forms of 20(R)-Rg3 and extensive application.     

Formulation studies for mirtazapine orally disintegrating tablets

Abstract

Objective: Orally disintegrating tablets (ODTs) recently have gained much attention to fulfill the needs for pediatric, geriatric, and psychiatric patients with dysphagia. Aim of this study was to develop new ODT formulations containing mirtazapine, an antidepressant drug molecule having bitter taste, by using simple and inexpensive preparation methods such as coacervation, direct compression and to compare their characteristics with those of reference product (Remereon SolTab).

Materials and methods: Coacervation method was chosen for taste masking of mirtazapine. In vitro characterization studies such as diameter and thickness, weight variation, tablet hardness, tablet friability and disintegration time were performed on tablet formulations. Wetting time and in vitro dissolution tests of developed ODTs also studied using 900?mL 0.1?N HCl medium, 900?mL pH 6.8 phosphate buffer or 900?mL pH 4.5 acetate buffer at 37?±?0.2?°C as dissolution medium.

Results: Ratio of Eudragit® E-100 was chosen as 6% (w/w) since the dissolution profile of A1 (6% Eudragit® E-100) was found closer to the reference product than A2 (4% Eudragit® E-100) and A3 (8% Eudragit® E-100). Group D, E and F formulations were presented better results in terms of disintegration time. Dissolution results indicated that Group E and F formulations showed optimum properties in all three dissolution media.

Discussion: Formulations D1, D4, D5, E3, E4, F1 and F5 found suitable as ODT formulations due to their favorable disintegration times and dissolution profiles.

Conclusion: Developed mirtazapine ODTs were found promising in terms of showing the similar characteristics to the original formulation.     

Characterization of phyto-nanoparticles from Ficus krishnae for their antibacterial and anticancer activities

Background: Ovarian cancer is deadliest of fifth leading cause of death in women worldwide. This is due to advanced-stage disease rate associated with the development of chemoresistance. Hence, the current study emphasizes the process of synthesis of silver nanoparticles (AgNPs) from green chemistry method. Ficus krishnae is a perennial plant, native to India, used in folklore medicine to treat various diseases.

Objective: For the development of reliable, ecofriendly, less expensive process for the synthesis of AgNPs against bacterial and ovarian cancer.

Methodology: The synthesis of silver nanoparticles from stem bark of Ficus krishnae was carried out. The synthesized nanoparticles are subjected by UV-Vis spectrophotometer, scanning electron microscopy (SEM), X-ray diffraction (XRD) analysis and FTIR analysis. The antibacterial efficacy also determined by disc diffusion method, MIC, CFU and growth curve. In vitro cytotoxicity effect of aqueous extract and AgFK nanoparticle in ovarian cancer cell line by MTT assay was performed.

Results: The formation of AgNPs was confirmed by UV-VIS spectroscopic absorbance shown that peak at 435?nm. XRD photograph has indicated the face-centered cubic structure of the synthesized AgNPs. SEM study demonstrated that the size from 160 to 260?nm with interparticle distance, whereas shape is spherical. The particle size were ranging from 15 to 28?nm determined by XRD pattern. The antibacterial and cytotoxicity activity of this nanoparticle has showed a potential activity when compared with standards.

Conclusion: The present study confirms that the biosynthesized AgNPs from Ficus krishnae stem bark extract have a great affiance as antibacterial and anticancer agent.     

Natamycin niosomes as a promising ocular nanosized delivery system with ketorolac tromethamine for dual effects for treatment of candida rabbit keratitis; in vitro/in vivo and histopathological studies

Objectives: This study was aimed to develop dual-purpose natamycin (NAT)-loaded niosomes in ketorolac tromethamine (KT) gels topical ocular drug delivery system to improve the clinical efficacy of natamycin through enhancing its penetration through corneal tissue and reducing inflammation associated with Fungal keratitis (FK).

Significance: Nanosized carrier systems, as niosomes would provide great potential for improving NAT ocular bioavailability.NAT niosomal dispersion formulae were prepared and then incorporated in 0.5%KT gels using different mucoadhesive viscosifying polymers.

Methods: Niosomes were prepared using the reverse-phase evaporation technique. In vitro experimental, and in vivo clinical evaluations for these formulations were done for assessment of their safety and efficacy for treatment of Candida Keratitis in Rabbits. In vitro release study was carried out by the dialysis method. In vivo and histopathological studies were performed on albino rabbits.

Results: NAT niosomes exhibited high entrapment efficiency percentage (E.E%) up to96.43% and particle size diameter ranging from 181.75?±?0.64 to 498.95?±?0.64?nm, with negatively charged zeta potential (ZP). NAT niosomal dispersion exhibited prolonged in vitro drug release (40.96–77.49% over 24h). NAT-loaded niosomes/0.5%KT gel formulae revealed retardation in vitro release, compared to marketed-product (NATACYN^®) and NAT-loaded niosomes up to57.32% (F8). In vivo experimental studies showed the superiority for F8 in treatment of candida keratitis and better results on corneal infiltration and hypopyon level. These results were consistent with histopathological examination in comparison with F5 and combined marketed products (NATACYN^® and Ketoroline^®).

Conclusions: This study showed that F8 has the best results from all pharmaceutical in vitro evaluations and a better cure percent in experimental application and enhancing the prolonged delivery of NAT and penetrating the cornea tissues.     

Compressive behaviour of Neovius Triply Periodic Minimal Surface cellular structure manufactured by fused deposition modelling

ABSTRACT

Compressive behaviour of Triply Periodic Minimal Surface type Neovius structure is investigated. The structure was manufactured by Fused Deposition Modelling (FDM) Additive Manufacturing technology in ABS material. The Neovius cellular structures with four different unit cell sizes of 8, 10, 12 and 14?mm with the volume fractions of 15%, 20% and 25% were investigated. Morphology of the samples was analysed through optical microscopy, and the pore and strut sizes were compared for the designed model and FDM samples. During the compression test, the Neovius structure showed the oscillating behaviour of the stress–strain curve with the larger unit cell size showing fracture across multiple layers in different orientations. Optical analysis of the struts after the compression tests showed that struts are the weakest link with the highest stressed area and the fracture was seen initiated at the struts. Both compressive modulus and strength increased with the increase in volume fraction.     

THE REACTION OF C60F20 WITH ANTHRACENE: FORMATION OF AN OXIDISED-ANTHRACENE 1 : 1 COMPLEX

ABSTRACT

The reaction of C₆₀F₂₀ (“Saturnene”) with anthracene yields a white 1?:?1 cycloadduct (1) in which two oxygen atoms have inserted into the anthracene framework due to fullerene-catalysed oxidation; the ¹⁹F NMR spectrum of the product shows evidence of through-cage homoconjugation.     

Poly (butylene adipate-co-butylene terephthalate) nanoparticles prepared by electrospraying technique for docetaxel delivery in ovarian cancer induced mice

Objective: Ovarian cancer is still a major cause of morbidity and mortality. Docetaxel (DTX) is one of the most notable cytotoxic agents for treatment of ovarian cancer. However, its side effects proposed considerable problems to the patients.

Significance: Polymeric nanoparticles (NPs) of poly (butylene adipate-co-butylene terephthalate) (Ecoflex^®), a biodegradable and biocompatible polymer, were prepared for the first time by the upgradeable electrospraying technique.

Methods: The formulation and procedure variables were optimized using Design Expert software, and effect of each variable on particle size, particle size distribution, drug entrapment efficiency, and drug release of the NPs were evaluated. Then, in vitro cytotoxicity, cellular uptake, X-ray diffraction pattern, and morphological characteristics of the optimized NPs were evaluated. Finally, in vivo efficacy of the DTX-loaded NPs was evaluated on tumor bearing nude mice.

Results: The optimum condition for production of NPs included voltage of 20?kV, 12?cm distance between electrodes, feeding rate of 1?mL/hr, polymer to drug ratio of 3:1, 1 w/v% of Pluronic-F127 and dichloromethane to dimethyl formamide ratio of 2.7:1. Fluorescent microscopy test showed the NPs were successfully up-taken by ovarian cancer cells. In vitro cytotoxicity test confirmed no cytotoxic effect caused by blank NPs, while cell viability of the DTX loaded NPs was significantly lower than the free DTX (p?p?Conclusion: The Ecoflex^® NPs could potentially provide a suitable alternative for currently available formulations of DTX.