High Encapsulation Research Articles

Andrographolide-loaded PLGA-PEG-PLGA micelles to improve its bioavailability and anticancer efficacy

Background: Andrographolide (ADG) isolated from Andrographis paniculata exhibits anti-inflammatory and anticancer activities, but high hydrophobicity and poor bioavailability greatly restricts its clinical application.Objectives: In this study, ADG was encapsulated in a micelle formulation based on poly (D,L-lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly (D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) amphiphilic triblock copolymers, in order to enhance the anticancer efficacy and bioavailability in vivo.Methods: The physicochemical properties of the ADG-loaded PLGA-PEG-PLGA micelles were investigated for encapsulation efficiency, particle size, zeta potential and critical micelle concentration. These micelles were further evaluated for in vitro cytotoxicity, including proliferation inhibition, cell cycle arrest and pro-apoptosis effects against human breast cancer MAD-MB-231 cells, cellular uptake and pharmacokinetics study in rat.Results: ADG-loaded PLGA-PEG-PLGA micelles had a high encapsulation and loading efficiency of about 92 and 8.4% (w/w), respectively, and a stable particle size of 124.3 ± 6.4 nm. In vitro cytotoxicity testing demonstrated that ADG-loaded PLGA-PEG-PLGA micelles exhibited higher proliferation inhibition, cell cycle arrest at the G2/M phase and pro-apoptosis effects in MAD-MB-231 cells, which would be contributed to higher efficiency of cellular uptake and intracellular transport. Further, the plasma AUC(0 – ∞) and mean resident time of ADG-loaded PLGA-PEG-PLGA micelles were increased by 2.7- and 2.5-fold, respectively, when compared to the raw suspension.Conclusion: All of these investigations suggest that PLGA-PEG-PLGA micelles may be a potential drug delivery strategy for improving ADG bioavailability and efficacy in cancer therapy.

Influence of mixture ratio and pH to solidification/stabilization process of hospital solid waste incineration ash in Portland cement

Solidification/stabilization (S/S) is an established utilization technology to treat hazardous wastes. This research explored the influence of pH (3–12) on the immobilization of heavy metals present in five mixtures of hospital solid waste incinerator ash and Portland cement, following two different processes of waste solidification/stabilization (cement hydration and granulation). In general, cement hydration process resulted in more stable products than granulation process. A high ash content in the mixture with Portland cement (60wt%) resulted in the highest immobilization of Pb2+ and Cu2+, while a low ash content in the mixture (10wt%) resulted in the lowest leachability of Zn2+. When ash and Portland cement was mixed in equal proportions (50wt%) the highest encapsulation was observed for Ni2+, Cd2+ and Cr3+. Neutral and weak alkaline pH values within the range pH=7–8 resulted in the lowest leachability of the monitored heavy metals.

Preparation and In Vitro Evaluation of Ethylcellulose and Polymethacrylate Resins Loaded Microparticles Containing Hydrophilic Drug.

Objective. The purpose of the recent study was to prepare and estimate sustained release of Ethylcellulose (300 cps) and Eudragit (RS 100 and RL 100) microparticles containing Propranolol hydrochloride used as a treatment of cardiovascular system, especially hypertension. Method. Propranolol hydrochloride was microencapsulated with different polymers (Ethylcellulose, Eudragit RS, and Eudragit RL) using modified hydrophobic (O/O) solvent evaporation method using 1 : 1 combination of acetone and isopropanol as the internal phase. Obtained microparticles were showing higher batch yield with higher encapsulation efficiency. Microparticles were prepared with different ratios of 1 : 1, 1 : 3, 1 : 5, and 1 : 7 (%, wt/wt) using span 80 (%, v/v) as a surfactant. Results. The influence of formulation factors like drug: polymer ratio, internal phase, and type of polymers on obtained microparticles was characterized with respect to particle size distribution, encapsulation efficiency, percentage yield, FTIR, and FE-SEM. Higher encapsulation efficiencies were obtained with various polymers like Ethylcellulose (96.63 ± 0.5) compared to Eudragit RS 100 (83.70 ± 0.6) and RL 100 (89.62 ± 0.6). The in vitro release study was characterized by initial burst. Conclusion. The result of study displays that Ethylcellulose and Eudragit loaded microparticles of Propranolol hydrochloride can be effectively prepared using modified hydrophobic emulsification solvent evaporation technique. Therefore, the modified hydrophobic emulsion technique can also be applied to the preparation of microparticles for low molecular weight and highly water soluble drugs.

P567 SERIAL MEASUREMENTS DO NOT INCREASE PERFORMANCE OF ALPHA-FETOPROTEIN FOR HEPATOCELLULAR CARCINOMA SURVEILLANCE IN HEPATITIS B VIRUS-RELATED LIVER CIRRHOSIS

defined eIF3 subunit (eIF3m) has not characterized. Recently, reported that eIF3m expression affects cell proliferation and cell cycle progression in colon cancer and one of tumorigenesis-related genes, macrophage migration inhibitory factor (MIF) is affected by eIF3m. We investigated expressions of eIF3m and MIF in human HCCs via immunohistochemistry and their relations with clinicopathological parameters. Methods: Surgically resected HCCs from 114 patients were selected. Immunohistochemistry for anti-eIF3m and anti-MIF processed, using auto-immunostainer. Results: One hundred HCCs (87.7%) expressed eIF3m, low grade 20.2%, intermediate 45.6% and high 21.9%. eIF3m expressed predominantly at peripheries and invasive fronts of tumor nests. Higher expression significantly associated with high preoperative AFP, poor differentiation and septal formation (P = <0.0001, 0.0001, 0.0055). Fatty change, mononuclear cell infiltration, vascular invasion and progression tended to be associated with higher expression. MIF expressed in 103 of 114 HCCs (90.4%), low grade 43.0% and high 47.4%. High expression was significantly associated with high preoperative AFP and encapsulation (P =0.0123, 0.0142). Vascular invasion tended to be associated with high expression. Significant positive correlation was found between eIF3m and MIF expressions (P =0.0048). Higher MIF expression tended to be related with high recur probability. eIF3m or MIF expression was not an independent predictive factor for recur throughout multivariate analysis. Conclusions: eIF3m expression suggested to have a pivotal role in HCC progression and invasion with downstream regulation of MIF expression. MIF expression may be an important factor for prediction of HCC recur.

P566 THE CLINICAL-GUIDE RISK PREDICTION MODEL OF HEPATOCELLULAR CARCINOMA DEVELOPMENT IN CHRONIC HEPATITIS C PATIENTS AFTER INTERFERON-BASED THERAPY

defined eIF3 subunit (eIF3m) has not characterized. Recently, reported that eIF3m expression affects cell proliferation and cell cycle progression in colon cancer and one of tumorigenesis-related genes, macrophage migration inhibitory factor (MIF) is affected by eIF3m. We investigated expressions of eIF3m and MIF in human HCCs via immunohistochemistry and their relations with clinicopathological parameters. Methods: Surgically resected HCCs from 114 patients were selected. Immunohistochemistry for anti-eIF3m and anti-MIF processed, using auto-immunostainer. Results: One hundred HCCs (87.7%) expressed eIF3m, low grade 20.2%, intermediate 45.6% and high 21.9%. eIF3m expressed predominantly at peripheries and invasive fronts of tumor nests. Higher expression significantly associated with high preoperative AFP, poor differentiation and septal formation (P = <0.0001, 0.0001, 0.0055). Fatty change, mononuclear cell infiltration, vascular invasion and progression tended to be associated with higher expression. MIF expressed in 103 of 114 HCCs (90.4%), low grade 43.0% and high 47.4%. High expression was significantly associated with high preoperative AFP and encapsulation (P =0.0123, 0.0142). Vascular invasion tended to be associated with high expression. Significant positive correlation was found between eIF3m and MIF expressions (P =0.0048). Higher MIF expression tended to be related with high recur probability. eIF3m or MIF expression was not an independent predictive factor for recur throughout multivariate analysis. Conclusions: eIF3m expression suggested to have a pivotal role in HCC progression and invasion with downstream regulation of MIF expression. MIF expression may be an important factor for prediction of HCC recur.

A review of polymeric biomaterials research for tissue engineering and drug delivery applications at the Centre for Biomedical and Biomaterials Research, Mauritius

The purpose of this review article is to showcase research in the area of polymeric nanobiomaterials and nanocarriers for drug delivery, especially on the economically fast-growing African continent where research in the field of advanced polymers and nanomedicine can play an important role in addressing crucial health issues. In biomaterials research, we have developed a new family of poly(ester-ether)s and shown that poly(methyl dioxanone) (PMeDX) can efficiently assist in fine-tuning mechanical and biological properties of scaffolds for tissue engineering applications. Interestingly, degradation of scaffold films was proceeded by bulk erosion, whereas that of fibres took place by a surface erosion mechanism. In vitro cell culture studies conducted using human dermal fibroblasts showed that the electrospun polydioxanone/poly(methyl dioxanone) (PDX/PMeDX) nanofibrous scaffolds supported better cell attachment and proliferation compared to electrospun PDX. Our main focus has been on the engineering of various self-assembled nanomicelles based on a biodegradable poly(dioxanone-co-methyl dioxanone) core and hydrophilic poly(ethylene glycol) or poly(vinyl pyrolidone) or polylysine or oligoagarose shell. High drug encapsulation efficiency and prolonged drug release have been demonstrated. Adjustment of the dioxanone to methyl dioxanone ratio gives a range of copolymers whose physicochemical and biological properties can be tuned to meet specific drug delivery requirements. The efficacy of these copolymers to encapsulate and release anti-inflammatory, anti-tuberculosis drugs and anti-cancer drugs has been tested and are quite promising.

Hydrophobic penetrating peptide PFVYLI-modified stealth liposomes for doxorubicin delivery in breast cancer therapy

Based on the hydrophobic interaction with biomembranes, PFVYLI (PFV), a hydrophobic penetration peptide (HPP), was initially introduced to modify doxorubicin-loaded stealth-sustained liposomes (PFV-SSLs-DOX) against different breast cancer cell phenotypes irrespective of their receptor expression or antigen presence. The physicochemical characteristics of PFV-SSLs were determined with approximately 100 nm size, satisfactory distribution and high encapsulation. In addition, drug release experiments demonstrated that modification with PFV has a negligible influence on the release profile of liposomes. Surface plasmon resonance (SPR) analysis revealed that PFV-modified liposomes could increase the binding proportion of PFV-SSLs with a model cell membrane. It was demonstrated that modification with PFV highly facilitated the intracellular delivery of DOX-loaded liposomes and enhanced cytotoxicity via a hydrophobic interaction. An endocytosis inhibition assay revealed a combination of cellular internalization mechanisms for PFV-SSLs involving lipid raft and clathrin-mediated endocytosis in a temperature-dependent manner. The PFV-modified liposomes displayed more lasting accumulation in the tumor and better tumor growth inhibition with relatively low systemic and cardiac toxicity. In conclusion, PFV-SSLs might be a promising delivery system for the delivery of different therapeutic or imaging agents to heterogeneous tumors. More significantly, this study provides a new perspective on developing HPP-modified drug delivery system for antitumor therapy.

111 Cryopreservation of stem cells inside alginate 3D constructs after high-voltage encapsulation

Application of stem cells in regenerative medicine require improving cryopreservation protocols for long term storage, especially for tissue-imitating 3D constructs containing cells. Encapsulation of stem cells into alginate-based 3D constructs that repeat an extracellular matrix may provide a mild environment during cryopreservation as well as the possibility for large-scale expansion. Furthermore, smaller alginate micro-beads ⩽3 μm offer additional advantages over larger ones due to higher specific surface area, less water content and improved heat and mass transfer. The gel-like structure and mild environment inside alginate micro-beads may affect the metabolic activity of encapsulated cells post-cryopreservation. The effects of high voltages, alginate encapsulation and pre-incubation time on morphology, viability and proliferation of MSCs post-cryopreservation were evaluated. Mesenchymal Stem Cells derived from the Common marmoset monkey Callithrix jacchus (MSC) were encapsulated into 1.5% (w/v) sterile medium viscosity unmodified alginate (Sigma Aldrich, filter-sterilized using 0.8–0.45–0.22 mm filter set) with a concentration 1*106 cells per ml of alginate using electro-spraying method. Final alginate micro-beads were obtained with less then 300 μm in diameter under the next process parameters: applied voltages 15, 20 and 25 kV, spraying distance 10 cm, and alginate flow rate 10 ml/h. As a negative control to high voltages, the air flow encapsulation was run in parallel. Micro-beads (0.5 ml) containing MSCs (0.5*106 cells) were either immediately frozen after encapsulation (0 h) or cultured overnight prior to cryopreservation (24 h). Cryopreservation was conducted with 1 °C/min cooling rate down to −80 °C with 10% Me2SO (v/v) as a cryoprotective agent. After 24 h of storage at low temperatures micro-beads were thawed at 37 °C with further removing of alginate using 55 mM sodium citrate for 2 min with gentle shaking. Then MSCs were either seeded for MTT test at 104 cells/well immediately after thawing (protocol from manufacturer) or cultured for 5 days followed by MTT assay. Membrane integrity of encapsulated cells before cryopreservation and after thawing was evaluated by Trypan Blue exclusion method. Metabolic activity and proliferation efficiency of MSCs were evaluated using MTT Nonradioactive Proliferation Assay (CellTiter 96, Promega, USA). The MTT data were normalized on respective control groups. The one-way ANOVA was run for statistical analysis of obtained results. MSCs can be encapsulated into alginate micro-beads with desired concentration and without significant changes in viability and metabolic activity post-encapsulation. MSCs showed normal morphology, attached and proliferated well after thawing. The incubation of MSCs inside alginate micro-beads prior to cryopreservation resulted in lower proliferation rate as compared to immediately frozen (18 ± 6% and 45 ± 8% in respect to native control) and at the same rate as frozen control. The same behavior was observed for re-passage efficiency of encapsulated and frozen MSCs. However, immediately frozen cells after encapsulation recovered at the same rate as native control, indicating an effectiveness of cell cryopreservation inside alginate micro-beads. This study shows an importance of cell cryopreservation inside unmodified alginate directly after encapsulation. Due to toxic effect of Me2SO, cryopreservation of MSCs inside alginate 3D structures using other less toxic CPAs will be conducted. Source of funding: This work is supported by funding from the Cluster of Excellence REBIRTH (DFG EXC 62/1). Conflict of interest: None declared. gryshkov@imp.uni-hannover.de

Development of curcumin-loaded poly(hydroxybutyrate-co-hydroxyvalerate) nanoparticles as anti-inflammatory carriers to human-activated endothelial cells

Curcumin (Cm)-loaded poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) nanoparticles (CmPN) were obtained and characterized and their effect on human endothelial cells (HEC) was assessed. Different CmPN formulations have been prepared using the emulsion solvent evaporation technique, and characterized for size, structure, Zeta potential, Cm entrapment efficiency, and in vitro Cm release. CmPN cytotoxicity and cellular uptake have been followed using HEC. Also, the effect of CmPN treatment on the p38MAPK signaling pathway in endothelial cells was investigated. The results obtained by electron and atomic force microscopy revealed the spherical shape of the CmPN formulation. Based on size and encapsulation efficiency, the CmPN formulation with the average diameter of 186 nm and with the highest encapsulation efficiency (83 %) has been used in the further studies. The release of Cm from CmPN was ~18 % after 8 h of incubation at 37 °C, followed by a slow release until 144 h, when it reached 44 %, indicating a controlled release. CmPN are taken up by HEC and exhibited low cytotoxicity at concentrations up to 10 μM. The pre-treatment of HEC with CmPN before exposure to tumor necrosis factor-alpha (TNF-α) determined a decrease of p38MAPK phosphorylation. In conclusion, Cm encapsulated into PHBV nanoparticles, at concentration up to 10 μM, has low cytotoxicity and display anti-inflammatory activity on TNF-α-activated HEC by suppressing the phosphorylation of p38MAPK.

Preparation and Structure Characterization of Poly(lactide-co-ethylene carbonate) Microspheres

The purpose of this study was to prepare and characterize tinidazole-loaded poly (lactide-co-ethylene carbonate) (PLEC) microspheres. These biodegradable microspheres were prepared by solvent evaporation method. The effect of selected emulsifier, polymer type, and ratio of tinidazole to PLEC were investigated. An aqueous gelatin solution used as emulsifier resulted in uniform microspheres with spherical surfaces. The PLEC microspheres exhibited rough surface and porous internal structures when compared with the PLA microspheres. The ratio of tinidazole to PLEC (1/10) exhibited higher encapsulation efficiency and drug loading of tinidazole. The introduction of hydrophilic PEC content influenced the structure and encapsulation efficiency of microspheres. These results suggest that the novel PLEC microspheres can be useful for drug delivery systems.

Development and Application of Nanoparticles Synthesized with Folic Acid Conjugated Soy Protein

In this study, soy protein isolate (SPI) was conjugated with folic acid (FA) to prepare nanoparticles for target-specific drug delivery. Successful conjugation was evidenced by UV spectrophotometry and primary amino group analysis. An increase in count rate by at least 142% was observed in FA-SPI nanoparticles compared to the nonconjugated ones, whereas the particle size was decreased upon FA conjugation. This was probably attributed to the substitution of positively charged lysine residues by the FA backbone. The ζ-potential ranged from -36 to -42 mV depending on the conjugation degree, indicating desirable dispersion stability. Curcumin as a model drug was encapsulated successfully into FA-SPI nanoparticles, evidenced by X-ray diffraction study. The highest encapsulation and loading efficiencies were around 92.7% and 5.4%, respectively, which were significantly higher (P < 0.05) than those with nonconjugated SPI nanoparticles. In addition, a faster and more complete release of curcumin was observed for FA-SPI nanoparticles in PBS/Tween 20 buffer. Cell culture study showed that conjugation of FA resulted in an increase in cellular uptake by at most 93% in Caco-2 cells. These results suggested that FA-SPI is a potential wall material for encapsulation and enhanced delivery of anticancer drugs.

Design Key Points for High Power LED Encapsulation

LED performance was significantly improved because of the improvement of encapsulation design and materials properties. The design key points were reviewed in point view of optical, electrical, thermal, and reliability consideration. It was concluded that the packaging design should be simultaneously implemented with the chip design, integrally considering the optics, electrics, thermal, and reliability together. The interfacial thermal resistance and stress from packaging also play critical roles for the optical efficiency and reliability of packaged LED device.

Surface modification of poly (l-lactic acid) microspheres for site-specific delivery of ketoprofen for chronic inflammatory disease

The purpose of this research was to investigate the potential of surface modified Poly (l-lactic acid) (PLA) microspheres as a carrier for site-specific delivery of anti-inflammatory drug, ketoprofen, for the treatment of rheumatoid arthritis. Microspheres were prepared by solvent evaporation method using 20% w/w PLA in methylene chloride and 100 mL of a 2.5% poly vinyl alcohol (PVA) solution. Formulations were optimized for several processing parameters like drug to polymer ratio, stirring rate and volume of preparation medium etc. The surface of PLA microspheres was modified with gelatin to impart fibronectin recognition. The microspheres were characterized by surface morphology, size distribution, encapsulation efficiency, and by in vitro drug release studies. The prepared microspheres were light yellow, discrete, and spherical. Formulation with optimum drug to polymer ratio exhibited smallest vesicle size (43.02), high drug encapsulation efficiency (81.11) and better process yield (83.45). The release of drug was extended up to 24 h with Higuchi pattern of drug release. The in vivo results showed that the gelatin modified formulation reduced paw edema at greater extent than pure drug and PLA microspheres and it could be a promising carrier system for controlled and site-specific delivery of ketoprofen with possible clinical applications.

Optimization of Formulation Variables to Increase Antigen Entrapment in PLGA Particles

Efficient antigen entrapment is a key factor in preparation of poly (lactide-co-glycolide) acid (PLGA) vaccine formulations when the antigen is of short supply. This study presents a systematic approach in the testing of formulation variables with the objective to increase antigen entrapment in particles when the antigen stock concentration was low. Some of the experimental variables tested were poly (vinyl) alcohol (PVA) concentration in the inner (W1) and outer (W2) aqueous phase, W1/oil (O) phase ratio and choice of organic solvent. The double emulsion solvent evaporation technique was applied to prepare PLGA particles with sonication as the emulsifying force. To measure antigen entrapment efficiency, the antigen (bovine serum albumin, BSA) was isotope labeled with 125iodine (125I). Our results demonstrated that a low PVA concentration in the inner aqueous (W1) phase was beneficial to achieve a high encapsulation efficiency of antigen. On the contrary, in the outer aqueous (W2) phase, a high PVA concentration favored antigen entrapment. We also demonstrated that decreasing the W1 to O/polymer ratio contributed to increased entrapment efficiency. Testing different organic solvents (ethyl acetate, dichloromethane and chloroform), either alone or in combination, revealed that using chloroform as solvent resulted in the highest encapsulation of antigen and the highest production yield. Some of the results presented in this work are in disagreement with well-established formulation variables from previous studies.

Uptake pathways and subsequent nucleus targeting of tat-conjugated gelatin-siloxane nanoparticles as nonviral gene vector

Novel hybrid biomaterial of Tat peptide modified gelatin-siloxane nanoparticles (Tat-GS NPs), with positive surface potential was synthesised through a two-step sol-gel process. The particles were subsequently tested in vitro with HeLa cells by fluorescent activitated cell sorter analysis, confocal laser scanning microscopy, and transmission electron microscopy to determine whether the functionalisation with Tat peptide allowed particles to transfer across the cell membrane and locate in the nucleus. Our current results indicated that the internalisation of Tat-GS NPs in HeLa cells is time- and concentration- dependent. Moreover, Tat-GS NPs could penetrate the nucleus membrane and enter into nucleus. The Tat-GS/pDNA nanocomplexes were formulated with higher encapsulation efficiency, and exhibited efficient transfection in vitro. Tat-GS NPs are thus considered as novel non-viral vectors will be widely used in further study.

Microencapsulation of self-microemulsifying systems: Optimization of shell-formation phase and hardening process

The preparation of microcapsules with a self-microemulsifying system (SMES) core using a vibrating nozzle technology was improved with regard to process reproducibility and core phase retention. The microcapsule shell was optimized for composition of the alginate-pectin (A/P) ratio and hydrophilic filling agent content. The best-shaped microcapsules with highest encapsulation efficiency for furosemide-loaded SMES were obtained from the shell-formation phase with an A/P ratio of 25:75, containing 10% lactose, which was hardened through a one-step process. Fluid-bed dried microcapsules were examined for their release characteristics and swelling behavior of the polymeric matrix. Incorporation of hydrophilic filling agents in the shell-formation phase was shown to be successful in limiting the leakage of the core phase during the microcapsule production and drying processes. Moreover, the addition of different fillers also allows the drug release profile from Ca-alginate/pectinate microcapsules with a self-microemulsifying core to be modified.

Study on the Preparation Process of Salicylic Acid Liposome Gel

Objective To optimize the preparation technology of salicylic acid liposome gel. Method Salicylic acid liposome was prepared with reverse evaporating method, and liposome gel was prepared using carbomer-940 as matrix. The encapsulation efficiency and leaking percentage of salicylic acid liposome was determined with centrifugal method, and the preparation technology of liposome gel was optimized with orthogonal test. Results The encapsulation efficiency of salicylic acid liposome was 75.86％, leaking percentage was 1.37％. The optimal preparation technology of liposome gel were carbomer 3g, glycerol 15g, mixing temperature 40°C, mixing time 15min. Conclusion Reverse evaporating method was a good method to prepare salicylic acid liposome with higher encapsulation efficiency and better stability. The optimized preparation process of liposome gel was desirable, and the characteristics of product was stable and uniform.

Chemical stability enhancement and cytotoxicity reduction of papain loaded in PLGA nanospheres

Poly(lactic-co-glycolic acid) (PLGA) nanospheres loaded with papain were prepared by the emulsion solvent diffusion in water (ESD) and the w/o/w emulsion solvent evaporation (ESE) methods. The nanosphere loaded with papain from the ESE method gave smaller particle sizes (220–232 nm) and higher encapsulation efficiency of about two-folds than those from the ESD method. The morphology of the nanospheres loaded with papain prepared by the ESE method exhibited spherical shape and smooth surface investigated by SEM and TEM. The release profile of papain from the PLGA nanospheres of the ESD and ESE method indicated two phases with an initial rapid phase of 6 h and followed by the slow release phase of 48 h. The unloaded PLGA nanospheres from the two methods did not show any cytotoxicity in human skin fibroblasts, while the unloaded papain gave toxicity more than the loaded papain of 1.5 times. Papain loaded in PLGA nanospheres prepared by the ESE method was more chemical stable than the unloaded papain of eight and three times when kept at 4°C and 25°C for 6 weeks, respectively. The developed stable and low cytotoxic nanosphere loaded with papain can be further developed as topical products.

Successful factorial design for the optimization of methylprednisolone encapsulation in biodegradable nanoparticles

Due to their crystalline nature, the encapsulation of hydrophobic corticosteroids within polymeric nanoparticles by o/w solvent evaporation method is often difficult to achieve. The aim of this study was to evaluate the effect of both process and formulation parameters on the encapsulation of a model corticosteroid: methylprednisolone (MP). For this purpose, a 32factorial design was performed evaluating the effects of the concentration of emulsifiers and sonication time on the manufactured nanoparticles, followed by a multiresponse optimization. The study also included the evaluation of other parameters such as the type of organic solvent used, polymer characteristics and the initial mass of drug. The optimal nanoparticle formulation using 0.25% (w/v) of emulsifying agent (Polyvinyl-alcohol, PVA) and 5 min of sonication was then characterized. The highest encapsulation was obtained with an organic phase consisting of acetone: dichloromethane (1:1), polyD,L-lactide-co-glycolide (PLGA) 50:50 as polymer and an initial mass of 6.6 mg of methylprednisolone. Nanoparticles size and ζ potential of optimized formulation were respectively around 230 nm and −14 mV. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) demonstrated that the drug was molecularly dispersed within the nanoparticles. Release study showed that MP-loaded nanoparticles sustained drug release for up to 120 h. This study reflects the importance of factorial design to optimize the manufacture of nanoparticles encapsulating hydrophobic drugs.

Comparative evaluation of cyclosporine A/HPβCD-incorporated PLGA nanoparticles for development of effective ocular preparations

To improve poor water solubility of cyclosporine A (CsA), hydroxypropyl-beta-cyclodextrin (HPβCD) was incorporated into the nanoparticle formulation. Solid complexes of CsA with HPβCD in different ratios were prepared by the kneading method. CsA containing alone or in combination with HPβCD in poly-lactide-co-glycolide (P-CsA or P-CsA-HPβCD) nanoparticles were prepared by the emulsification solvent evaporation method. The mean size of CsA-loaded NPs was found to be approximately 220 nm. The solubility of CsA was significantly improved and the phase solubility diagram of CsA–HPβCD systems showed an AL type phase. Nanoparticles showed high CsA encapsulation efficiency (88%) and production yield (89%). Release rate was increased by the presence of HPβCD and total cumulative release ranged from 75% to 96% in 24 h. In vitro cytotoxicity study assay resulted in a low toxicity for all types of nanoparticles. After 6 h incubation period, the cellular uptake was found at 33% and 32% for P–CsA and P–HPβCD–CsA nanoparticles, respectively.