Antioxidant activity and controlled release analysis of red ginger oleoresin (Zingiber officinale var rubrum) encapsulated in chitosan cross-linked by glutaraldehyde saturated toluene

The aim of this study was to determine encapsulation efficiency, particle size, and characterization of red ginger oleoresin microcapsules such as controlled release, morphology microcapsule and also determine the antioxidant activity of red ginger oleoresin microcapsules. The red ginger oleoresin was dispersed in chitosan and stirred to form an emulsion, then added to corn oil and stirred again to form a second emulsion. Glutaraldehyde saturated toluene (GST) as a crosslinking agent was added dropwise into the emulsion and continues to be stirred for the solidification process. Chitosan microspheres filled with red ginger oleoresin were washed using petroleum ether followed by hexane and then dried in the oven. Controlled release analysis was carried out in a phosphate buffer medium at pH 7.4. Red ginger oleoresin microcapsules produced the highest encapsulation efficiency was 82.54 ± 3.5 with a mean diameter ranging from 110.12 ± 12.2 to 161.42 ± 40.1 µm. Cumulative release of red ginger oleoresin from microcapsules reached the highest level was 61.69 ± 1.3% from 2% chitosan concentration and 5 ml GST, and the lowest level was 50.01 ± 1.8% from 4% chitosan concentration and 20 ml GST after they were immersed in phosphate buffer for 72 h. The value of antioxidant activity was between 38.28 ± 0.07% and 61.99 ± 0.33%. The release mechanism based on the Korsmeyer-Peppas model was Fickian diffusion with a diffusion coefficient value of 1.332 × 10^?11–4.576 × 10^?13 cm²/s.     

Synthesis and characterization of polyurethane–urea microcapsules containing galangal essential oil: statistical analysis of encapsulation

Galangal essential oil (GEO) is known to possess antimicrobial activity (e.g. against Staphylococcus aureus). A way to increase oil lifetime in plants is encapsulation in polyurethane–urea (PUU) microcapsules. In this study, PUU microcapsules with GEO were synthesized by interfacial polymerization at oil–water interface in oil–water emulsion. A statistical analysis of the microcapsule size was successfully applied for characterization of the encapsulation process. Using the model of reversible aggregation, it was shown that the process of encapsulation takes place in the conditions of thermodynamic control. The polymerization conditions (agitation rate in the range 2000–10?000?rpm/min) are the key factors that affect the mean microcapsule size of primary capsules formed during encapsulation. Two complementary processes were determined the mean capsule size during a transformation of these primary microcapsules: break-up and coalescence of oil droplets in the oil-in-water emulsion. The agitation rate does not influence the coalescence of the oil droplets, but the threshold value of agitation speed (in this system 4000?rpm/min) does exist and that is what strongly increases break-up of oil droplets. The higher agitation rate resulted in smaller size of microcapsules (mean diameter decreasing from 5.6 to 4.9?µm for primary capsules and from 13.8 to 9.8?µm for secondary capsules) and with a narrower size distribution. The last mode of encapsulation allows the more effective use the shell material for encapsulating of larger amount of oil.     

Formulation and characterization of albumin microspheres containing norcantharidate for liver tumor targeting

Abstract

The objectives of this study were first to encapsulate norcantharidate into albumin microspheres by the emulsion crosslinking method and second to characterize the microspheres in terms of the morphological examination, particle size, and encapsulation efficiency. The in vitro release of norcantharidate from the microspheres was studied by using the dialysis bag method. Pharmacokinetics and biodistribution studies were used to evaluate the advantages of microspheres than the conventional formulations. The microspheres prepared by crosslink emulsion were with uniform size, smooth surface, spherical shape, and disperse evenly. The particle size was uniform (13.3?±?0.4?µm) and the encapsulation efficiency was 54.3?±?4.18%. In vitro release indicated that the norcantharidate microspheres had a well-sustained release efficacy and fitted Korsmeyer’s Peppas release model. In vivo studies showed that pharmacokinetics of norcantharidate microspheres could be described by the model of two-compartment after i.v. administration and had higher AUC inside liver and spleen than the injection group. No histological change occurred to the rat liver after the administration of norcantharidate microspheres.     

In vitro and in vivo properties of usnic acid encapsulated into PLGA-microspheres

Microparticles will probably play a promising role in the future of chemotherapy. These polymeric delivery systems are capable of maximizing the therapeutic activity while reducing side effects of anti-cancer agents. Usnic acid (UA) is a secondary metabolite produced by lichens, which exhibits an anti-tumour activity. In this study, PLGA-microspheres containing usnic acid from Cladonia substellata were prepared by the double emulsion method, with or without PEG as stabilizer. The morphology of the microspheres was examined by optical and scanning electron microscopy. The in vitro kinetic profile of usnic acid loaded-microspheres was carried out by dissolution testing. The usnic acid content was analysed by HPLC. The cytotoxicity of free and encapsulated usnic acid was evaluated against HEp-2 cells using the MTT method. The anti-tumour assay was performed in mice against Sarcoma-180 tumour (UA 15?mg?kg^?1 weight body/day) during 7 days. Animals were then sacrificed and tumour and organs were excised for histopathological analysis. Microspheres presented a smooth spherical surface with a mean diameter of 7.02?±?2.72?µm. The usnic acid encapsulation efficiency was ～100% (UA 10?mg 460?mg^?1 microspheres). A maximum release of 92% was achieved at the fifth day. The IC₅₀ values for free and encapsulated usnic acid were 12 and 14?µg?ml^?1, respectively. The encapsulation of usnic acid into microspheres promoted an increase of 21% in the tumour inhibition as compared with the free usnic acid treatment. In summary, usnic acid was efficiently encapsulated into PLGA-microspheres and the microencapsulation improved its anti-tumour activity.     

Encapsulation and release characteristics of DCTN/PLGA microspheres

In the present study, poly (D,L-lactic-co-glycolic)-acid microspheres containing trans-Dehydrocrotonin (DCTN) were prepared by the double emulsion method. The hypoglycemic activity of DCTN-loaded microspheres was monitored in normal glycemic mice after administration of a daily dose of DCTN (50 mg kg^?1 body weight) for 7 days. Spherical microspheres with two populations of particles with 3.20 ± 0.10 and 7.60 ± 0.70 µm mean diameter size µm were observed. The encapsulation efficiency of DCTN was 85.5 ± 3.9%. The in vitro kinetic profile of DCTN from PLGA-microspheres was initially fast (burst effect of 19.4% at 2 h). Such a burst step was maintained until achieving 35.7±2.0% at 7h, followed by a gradual release of DCTN attaining a maximum drug release at 55.7 ± 2.6% within 30 h. DCTN was able to reduce glucose levels (14.3%) of normal glycemic animals and this effect was improved by its encapsulation into microspheres (26.8%). The optimum glucose levels in the blood of animals treated with DCTN suspension and DCTN-loaded microspheres were 119.21 ± 19.75 mg dL^?1 at day 5 and 103.08 ± 18.88 mg dL^?1 at day 7, respectively. DCTN-loaded microspheres are thus offered as a potential delivery system for the treatment of metabolic diseases characterized by hyperglycemia.     

The optimization of technological processes,stability and microbiological evaluation of innovative natural ingredients-based multiple emulsion

Abstract

For the last couple of decades, multiple emulsions were prepared either by the re-emulsification of primary emulsion or they were produced by an emulsion inversion and their technological peculiarities were widely investigated. The aim of our study was to investigate and determine the optimal technological parameters of innovative multiple emulsion, prepared directly—by addition of ethanolic rosemary extract in the presence of polymeric emulsifier—and evaluate its stability by experimental surface response design approach. The results revealed that simplified W/O/W emulsification process is stirring time and stirring speed sensitive: the change of stirring time from 5 to 15?min at 600?rpm resulted in increased viscosity (from 1705.6?±?62.2 to 3364.1?±?112.5?mPA/s) and smaller oil droplet size (from 33.09?±?1.51 to 17.81?±?0.78?μm), though the conductivity increased from 800?±?2 to 882?±?2 μS/cm (p?<?.05). The second mixing stage (1000?rpm) had a negative effect on the conductivity of W/O/W emulsion because of the inner aqueous phase encapsulation efficiency. Ethanolic rosemary extract was used as multifunctional agent: not only to form multiple emulsion but also to preserve it; microbiological assay confirmed its effectiveness. A stable W/O/W type drug delivery system was successfully created without additional technological stages, phase inversion or surfactants.     

A “drug cocktail” delivered by microspheres for the local treatment of rat glioblastoma

For the treatment of glioblastoma multiforme, an “anticancer drug cocktail” delivered by biodegradable poly-lactide-co-glycolide (PLGA)-microspheres is proposed. Celecoxib, etoposide, and elacridar were encapsulated by an oil/water emulsification solvent evaporation method. Drug-loaded microspheres were analyzed for their physicochemical properties and evaluated in a rat glioblastoma model. Microspheres had a mean diameter 10–20?µm, and encapsulation rates varied upon lipophilicity of the drug (celecoxib: 97.4?±?0.4%; elacridar: 98.1?±?0.3%; and etoposide: 38.7?±?8.3%). Drug release of celecoxib and elacridar resulted in a burst (t50: 3.1?h and 1.0?h, respectively) while etoposide release was slower (t50: 45.3?h). The comparison of celecoxib (p?=?0.021) and etoposide microspheres (p?=?0.002) as well as their combination (p?=?0.011) led to a significant increase in the probability of survival compared to blank microspheres. Local delivery of celecoxib and etoposide microspheres was found to be suitable for the treatment of glioblastoma in rats although simultaneous drug administration did not improve the therapeutic outcome.     

Lipid-core nanocapsules are an alternative to the pulmonary delivery and to increase the stability of statins

Abstract

Aims: Lipid-core nanocapsules (LNCs) loaded with simvastatin (SV, SV-LNC) or lovastatin (LV, LV-LNC) were formulated for pulmonary administration.

Methods: The LNC suspensions were characterized physicochemically, their stability was evaluated, and drug delivery by the pulmonary route was tested in vitro.

Results: The loaded LNCs had a particle size close to 200?nm, a low polydispersity index, and a zeta potential around ?20?mV. The encapsulation efficiency was high for SV (99.21?±?0.7%) but low for LV (20.34?±?1.2%). SV release from nanocapsules was slower than it was from SV in solution, with a monoexponential release profile, and the drug emitted and aerosol output rate was higher for SV-LNCs (1.58?µg/s) than for SV in suspension (0.54?µg/s).

Conclusions: SV-LNCs had a median aerodynamic diameter of 3.51?µm and a highly respirable fraction (61.9%), indicating that nanoparticles are a suitable system for efficient delivery of simvastatin to the lung.     

Microencapsulation of alpha-mangostin into PLGA microspheres and optimization using response surface methodology intended for pulmonary delivery

Abstract

Documented to exhibit cytotoxicity and poor oral bioavailability, alpha-mangostin was encapsulated into PLGA microspheres with optimization of formulation using response surface methodology. Mixed levels of four factors Face central composite design was employed to evaluate critical formulation variables. With 30 runs, optimized formula was 1% w/v polyvinyl alcohol, 1:10 ratio of oil to aqueous and sonicated at 2 and 5?min time for primary and secondary emulsion, respectively. Optimized responses for encapsulation efficiency, particle size and polydispersity index were found to be 39.12?±?0.01%, 2.06?±?0.017?µm and 0.95?±?0.009, respectively, which matched values predicted by mathematical models. About 44.4% of the encapsulated alpha-mangostin was released over 4 weeks. Thermal analysis of the microspheres showed physical conversion of alpha-mangostin from crystallinity to amorphous with encapsulated one had lower in vitro cytotoxicity than free alpha-mangostin. Aerodynamic diameter (784.3?±?7.5?nm) of this alpha-mangostin microsphere suggests suitability for peripheral pulmonary delivery.     

The ocular surface side effects of an anti-psychotic drug,clozapine

Purpose: The purpose of this study is to investigate the effects of long-term clozapine usage on tear film stability and corneal topographic parameters.

Material and methods: The study was conducted between March 2014 and November 2014. Thirty patients who were diagnosed of schizophrenia and have been under clozapine treatment for 2.73?±?0.73 years (range 2–4 years) were involved in this study (group 1). Thirty healthy subjects (group 2) who have statistically similar demographic features compared with the group 1, were involved as a control group. Full ophthalmologic examination with biomicroscopy and indirect ophthalmoscopy was applied. Corneal topographic parameters were measured using the Pentacam HR and Schirmer test was done. Statistical analysis of the subjects was evaluated by using SPSS (for Windows version 16.0; SPSS Inc., Chicago, IL) program.

Results: K₁ value was measured as 43.39?±?0.17?D (43–43.50?D) and K₂ value was measured as 43.39?±?0.06?D (43.30–43.50?D) in groups 1 and 2, respectively. In groups 1 and 2, K₂ values were noted as 43.86?±?0.27?D (43.50–44.50?D) and 43.72?±?0.18?D (43.50–44.00?D), respectively. Central corneal thickness was found to be 523.93?±?15.66?µm (495–554?µm) and 550.13?±?1.03?µm (520–580?µm) in groups 1 and 2, respectively. Corneal apex thickness was 525.86?±?15.75?µm (497–556?µm) in group 1 and 551.60?±?14.99?µm (521–581?µm) in group 2. The corneal thickness of thinnest location was 520.93?±?15.60?µm (492–551?µm) and 548.06?±?15.17?µm (518–578?µm) in groups 1 and 2, respectively. Corneal volume was determined as 58.13?±?3.46?mm³ (52–64?mm³) in group 1 and 60.73?±?3.76?mm³ (54–66?mm³) in group 2. The Schirmer test showed thichkness of 3.33?±?0.72?mm (2–4?mm) and 13.60?±?1.59?mm (11–16?mm) in groups 1 and 2, respectively. The mean fluorescein break-up time was 5.40?±?1.50?s (3–8?s) and 12.46?±?1.40?s (10–14?s) in groups 1 and 2, respectively. There was a statistically significant difference in the Schirmer test, fluorescein break-up time, central corneal thickness, corneal apex, and the thinnest corneal location thickness between the two groups.

Conclusion: Clozapine may induce dry eye syndrome and thus may lead to morphological alterations in corneal parameters through its anticholinergic and antidopaminergic activities. Because of these corneal alterations, one should be aware of evaluating patients having diseases like glaucoma or preoperative selection of corneal refractive surgery candidates.     

Gel network comprising UV crosslinked PLGA-b-PEG-MA nanoparticles for ibuprofen topical delivery

Ibuprofen is a non-steroidal anti-inflammatory drug for the treatment of Rheumatoid Arthritis and osteoarthritis. In this study, we prepared topical gel network for enhancement of ibuprofen penetration, maintenance of controlled release and increased patient compliance. Nanoparticles containing ibuprofen were prepared by means of emulsion formation/solvent diffusion method using synthesized copolymer. Nanoparticles were then conjugated with aminoethylmethacrylate, resulting in ibuprofen-loaded nanoparticles in PLGA-b-PEG-MA structure. Ibuprofen-loaded gel networks were developed by crosslinking nanoparticles via UV exposure. Suitability for topical application has been assessed through characterization of particle size, zeta potential, morphology, encapsulation efficiency, in vitro release, cytotoxicity and enhancement of in vitro wound healing. The mean diameter of nanoparticles was measured as 230?±?20?nm. Gel network formulations with higher particle size (2800?±?350?nm) and zeta potential (39.8?±?9.2?mV), depending on conjugation of methacrylate within copolymeric structure, and having encapsulation efficacy of 73.6?±?2.8% were prepared. The in vitro release of ibuprofen was sustained for more than 7?hours. Gel network improved collagen synthesis, type I collagen mRNA expression and fibrosis in dose dependent manner. Based on this, we can conclude that PLGA-b-PEG gel network might be a promising systems for the local delivery of ibuprofen in RA patients.     

5-Fluorouracil-loaded microspheres prepared by spray-drying poly(D,L-lactide) and poly(lactide-co-glycolide) polymers: Characterization and drug release

5-Fluorouracil (5-FU), a hydrosoluble anti-neoplastic drug, was encapsulated in microspheres of poly(D,L-lactide) (PLA) and poly(lactide-co-glycolide) (PLGA) polymers using the spray-drying technique, in order to obtain small size microspheres with a significant drug entrapment efficiency. Drug-loaded microspheres included between 47?±?11 and 67?±?12?µg 5-FU?mg^?1 microspheres and the percentage of entrapment efficiency was between 52?±?12 and 74?±?13. Microspheres were of small size (average diameter: 0.9?±?0.4–1.4?±?0.8?µm microspheres without drug; 1.1?±?0.5–1.7?±?0.9?µm 5-FU-loaded microspheres) and their surface was smooth and slightly porous, some hollows or deformations were observed in microspheres prepared from polymers with larger T_g. A fractionation process of the raw polymer during the formation of microspheres was observed as an increase of the average molecular weight and also of T_g of the polymer of the microspheres. The presence of 5-FU did not modify the T_g values of the microspheres. Significant interactions between the drug and each one of the polymers did not take place and total release of the included drug was observed in all cases. The time needed for the total drug release (28–129?h) was in the order PLA?>?PLGA 75/25?>?PLGA 50/50. A burst effect (17–20%) was observed during the first hour and then a period of constant release rate (3.52?±?0.82–1.46?±?0.26?µg 5-FU?h^?1 per milligram of microspheres) up to 8 or 13?h, depending on the polymer, was obtained.     

Investigation on the mechanical properties of polyurea (PU)/melamine formaldehyde (MF) microcapsules prepared with different chain extenders

There is lack of understanding on controlling of mechanical properties of moisture-curing PU/MF microcapsules which limited its further application. PU/MF microcapsules containing a core of isophorone diisocyanate (IPDI) were prepared with different chain extenders, polyetheramine D400, H₂O, triethylenetetramine and polyetheramine (PEA) D230 by following a two-step synthesis method in this study. Fourier transform infra-red (FTIR) spectroscopy, Malvern particle sizing, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). And micromanipulation technique was used to identify chemical bonds in the shell, size distributions, structure, thickness, and mechanical properties of microcapsules. The results show that PU/MF microcapsules were successfully prepared. Tr increased from 46.4?±?13.9 N/m to 75.8?±?23.3 N/m when extender changed from D400 to D230. And the Tr increased from 51.3?±?14.1 to 94.8?±?17.5 N/m when the swelling time increased from 1 to 3h. Morphologies of the shell were utilised to understand the mechanism of reactions in forming the shell materials.     

Microencapsulation of white champaca (Michelia alba D.C.) extract using octenyl succinic anhydride (OSA) starch for controlled release aroma

The objective of the study was to optimise the encapsulation of Michelia alba D.C. (MAD) extract using octenyl succinic anhydride (OSA) starch. The MAD extract (5–10?g/100?g of dry starch) and the OSA starch (25–100?g/100?ml of water) was used in microcapsule preparation and analysed for the physicochemical and encapsulation properties. The optimised formula using the MAD extract and the OSA starch were 15.00?g/100?g of dry starch and 96.32?g/100?g water, which provided the highest in yield recovery (40.65%?±?0.99) and encapsulation efficiency (68.91%?±?1.50), with the lowest moisture content (3.19%?±?0.06) and water activity (0.236?±?0.004). The aroma release from the optimum encapsulated powder in simulated artificial saliva fluid (SSF) suggested that linalool retention in microcapsules was higher than verbenone and 2-methyl butanoic acid. This study shows that the optimised formulation of MAD encapsulated flavour powder was found to be effective for controlling the aroma release.     

Preparation and characterization of textile-based carrier systems for anal fissure treatment

Anal fissure is common and painful disease of anorectum. In this study, microparticles containing nifedipine and lidocaine HCl were prepared by spray drying and applied to bio-degradable and bio-stable tampons. Characterization of microparticles was determined by visual analyses, mass yield, particle size measurement, encapsulation efficiency, drug loading and in vitro drug release. Mass yield was between 5.5 and 45.9%. The particle size was between 15.1 and 26.8?µm. Encapsulation efficiency were 96.142?±?5.931 and 85.571?±?3.301; drug loading were 65.261?±?3.914% and 37.844?±?4.339% of L2 and N1, respectively. Well-separated, mainly spherical microparticles with suitable properties were obtained. Optimum microparticles were applied to tampons. Physical properties and visual characteristics of tampons were investigated before and after binder application. In vitro drug release from tampons were also examined. According to the results, textile-based carrier systems loaded microparticles containing nifedipine and lidocaine HCl will be an effective and promising alternative for current anal fissure treatment.     

Sodium fusidate-poly(D,L-lactide-co-glycolide) microspheres: Preparation,characterisation and in vivo evaluation of their effectiveness in the treatment of chronic osteomyelitis

Purpose: The aim of this study was to prepare poly(D,L-lactide-co-glycolide) (PLGA) microspheres containing sodium fusidate (SF) using a double emulsion solvent evaporation method with varying polymer:drug ratios (1:1, 2.5:1, 5:1) and to evaluate its efficiency for the local treatment of chronic osteomyelitis.

Methods: The particle size and distribution, morphological characteristics, thermal behaviour, drug content, encapsulation efficiency and in vitro release assessments of the formulations had been carried out. Sterilized SF-PLGA microspheres were implanted in the proximal tibia of rats with methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. After 3 weeks of treatment, bone samples were analysed with a microbiological assay.

Results: PLGA microspheres between the size ranges of 2.16–4.12?µm were obtained. Production yield of all formulations was found to be higher than 79% and encapsulation efficiencies of 19.8–34.3% were obtained. DSC thermogram showed that the SF was in an amorphous state in the microspheres and the glass transition temperature (T_g) of PLGA was not influenced by the preparation procedure. In vitro drug release studies had indicated that these microspheres had significant burst release and their drug release rates were decreased upon increasing the polymer:drug ratio (p?<?0.05). Based on the in vivo data, rats implanted with SF-PLGA microspheres and empty microspheres showed 1987?±?1196 and 55526?±?49086 colony forming unit of MRSA in 1?g bone samples (CFU/g), respectively (p?<?0.01).

Conclusion: The in vitro and in vivo studies had shown that the implanted SF loaded microspheres were found to be effective for the treatment of chronic osteomyelitis in an animal experimental model. Hence, these microspheres may be potentially useful in the clinical setting.     

Preparation of novel solid lipid microparticles loaded with gentamicin and its evaluation in vitro and in vivo

Objective: To formulate and evaluate solid-reversed-micellar-solution (SRMS)-based solid lipid microparticles (SLMs) for intramuscular administration of gentamicin.

Methods: SRMS formulated with Phospholipon® 90G and Softisan® 154 were used to prepare gentamicin-loaded SLMs. Characterizations based on size and morphology, stability and encapsulation efficiency (EE%) were carried out on the SLMs. In vitro release of gentamicin from the SLMs was performed in phosphate buffer while in vivo release studies were conducted in rats.

Results: Maximum EE% of 90.0, 91.6 and 83.0% were obtained for SLMs formed with SRMS 1:1, 1:2 and 2:1, respectively. Stable, spherical and smooth SLMs of size range 9.80?±?1.46?µm to 33.30?±?6.42?µm were produced. The release of gentamicin in phosphate buffer varied widely with the lipid contents. Moreover, significant (p?<?0.05) amount of gentamicin was released in vivo from the SLMs.

Conclusion: SRMS-based SLMs would likely offer a reliable means of delivering gentamicin intramuscularly.     

Intraoperative corneal thickness measurements during corneal collagen cross-linking with isotonic riboflavin solution without dextran in corneal ectasia

Objective: To monitor the changes in corneal thickness during the corneal collagen cross-linking procedure by using isotonic riboflavin solution without dextran in ectatic corneal diseases.

Materials and Methods: The corneal thickness measurements were obtained before epithelial removal, after epithelial removal, following the instillation of isotonic riboflavin solution without dextran for 30?min, and after 10?min of ultraviolet A irradiation.

Results: Eleven eyes of eleven patients with progressive keratoconus (n?=?10) and iatrogenic corneal ectasia (n?=?1) were included in this study. The mean thinnest pachymetric measurements were 391.82?±?30.34?µm (320–434?µm) after de-epithelialization of the cornea, 435?±?21.17?µm (402–472?µm) following 30?min instillation of isotonic riboflavin solution without dextran and 431.73?±?20.64?µm (387–461?µm) following 10?min of ultraviolet A irradiation to the cornea.

Conclusion: Performing corneal cross-linking procedure with isotonic riboflavin solution without dextran might not induce corneal thinning but a little swelling throughout the procedure.     

Preparation and characterization of methotrexate-loaded microcapsules

Abstract

Methotrexate (MTX) has toxic effect to healthy tissues. Microencapsulation coats particles with a functional coat to optimize storage stability and to modulate release. In the present study, a new MTX encapsulated microcapsules were synthesized for controlling MTX release. Controlled drug release provides releasing of efficient dose and prevent drug side effect to tissues and also protects MTX from oxygen, pH and other interactions. MTX was encapsulated through biocompatible hyaluronic acid (HA) and sodium alginate (SA) with an encapsulation system to reduce its toxicity and for controlled release. The microcapsules prepared by vibrating nozzle were cross-linked with SA, HA and calcium chloride. Nozzle diameter and MTX concentration were changed according to loaded MTX and encapsulation efficiency were determined using HPLC. For the reliability of the data, validation studies of the HPLC method were performed. The precision of the method was demonstrated using intra- and inter-day assay relative standard deviation (RSD) values which are less than 2% in all instances. For the characterization of microcapsules, particle size, drug loading and in vitro drug release studies were performed. Diameters of MTX-loaded microcapsules were acquired approximately 160, 400 and 800?µm. Surface morphology of encapsulated microcapsules were displayed with light microscope. Eighty-nine percent MTX encapsulation efficiencies were achieved. Encapsulated MTX microcapsules showed controlled release when compared to pure MTX. While powder MTX dissolved completely in 10?min in the dissolution medium, MTX release from encapsulated MTX microcapsules became 40?h in 0.1?M PBS pH 7.4, including NaCl. MTX release from MTX-loaded microcapsules was reached to 79%. Moreover, drug efficiency was examined in vitro cell culture tests. Viability of 5RP7 cells were decreased to 88.5% for 96?h. When MTX was given directly to 5RP7 cells, viability of 5RP7 cells was decreased to 49.7% for 96?h. Flow cytometry studies also showed that, MTX microcapsules induced apoptosis. The goal of this study is to provide controlled release of MTX and to reduce the toxic effect of MTX.     

Controlled release behaviour of protein-loaded microparticles prepared via coaxial or emulsion electrospray

Biodegradable poly (lactic-co-glycolic acid) (PLGA) microparticles are an effective way to achieve sustained drug release. In this study, we investigated a sustained release model of PLGA microparticles with incorporated protein via either emulsion or coaxial electrospray techniques. PLGA (75:25) was used as the carrier, and bovine serum albumin as a model protein. Coaxial electrospray resulted in a type of core–shell structure with mean diameters of 2.41?±?0.60?µm and a centralised protein distribution within the core. Emulsion electrospray formed bigger microparticles with mean diameters of 22.75?±?8.05?µm and a heterogeneous protein distribution throughout the microparticles. The coaxial electrospray microparticles presented a much slighter burst release than the emulsion electrospray microparticles. Loading efficiency was significantly higher (p?<?0.05) in the coaxial group than emulsion group. This indicated that both emulsion and coaxial electrospray could produce protein-loaded microparticles with sustained release behaviour, but the former revealed a superior approach for drug delivery.