Preparation of liposomes entrapping essential oil from Atractylodes macrocephala Koidz by modified RESS technique

A modified technique of rapid expansion of supercritical solutions (RESS) was applied to incorporate essential oil extracted from Atractylodes macrocephala Koidz into liposomes. In the modified RESS process, both the liposomal materials and the essential oil were dissolved in the mixture of supercritical carbon dioxide (SC-CO₂)/ethanol and then the solution was sprayed into an aqueous medium through a coaxial nozzle to form liposomes suspension. The encapsulation performance of liposomes could be controlled by changing expansion processing conditions such as pressure, temperature of SC-CO₂ and the amount of ethanol. The entrapment efficiency, drug loading and average particle size of liposomes were found to be 82.18%, 5.18% and 173 nm, respectively, under the optimum conditions of at a pressure of 30 MPa, a temperature of 338 K and a ethanol mole fraction in SC-CO₂ [(x(CH₃CH₂OH)] of 15%. The formed liposomes appeared as double-layered colloidal spheres with a uniform and narrow particle size distribution. The physicochemical properties of liposomes including entrapment efficiency, dissolution rate and stability were complied with the provisions of Chinese pharmacopoeia. All these results indicate that the modified RESS technique is an innovative way for self-assembly of liposomes incorporation of multi-components extracted from Chinese traditional medicines in the SC-CO₂.     

Electrospray preparation of propranolol‐loaded alginate beads: Effect of matrix reinforcement on loading and release profile

In the present study, propranolol loaded‐calcium alginate beads were prepared from concentrated solutions of sodium alginate, using combined method of electrospray and ionotropic gelation. The objectives of the study were to increase the propranolol‐HCl loading and to decrease its initial burst release. However, the effects of voltage, nozzle diameter, flow rate, and concentration of sodium alginate on size of the beads and drug entrapment efficiency (DEE) were also investigated. The matrix of alginate beads was reinforced with dextran sulfate and/or coated with chitosan. The mean particle size of the beads, their swelling behavior, and drug entrapment efficiency were characterized. Furthermore, the drug release profiles from the prepared beads in simulated gastric fluid and intestinal fluid were evaluated and compared. Among the parameters that affected the electrospray of alginate, voltage had a pronounced effect on the size of beads. The size of beads was reduced to a minimum value on increasing the voltage. Furthermore, increasing the flow rate, alginate concentration, and nozzle diameter and decreasing the voltage led to improvement in DEE. Enhancing the alginate concentration as well as coating with chitosan and reinforcing with dextran sulfate led to increase of the encapsulation efficiency and therefore decrease of the drug release rate in both pHs. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41334.     

Preparation of PEGylated liposomes of docetaxel using supercritical fluid technology

The aims of this investigation were to develop a procedure to prepare and characterize docetaxel encapsulated PEGylated liposomes using supercritical carbon dioxide as antisolvent and optimize the process and formulation variables using response surface methodology. The process and formulation variables were optimized by “Box Behnken Design (BBD)” of response surface methodology (RSM) with temperature, pressure and CO₂ flow rate as independent variables and particle size and yield as dependent variables for process variables while the amount of hydrogenated soya phosphotidylcholine (HSPC), soya phosphotidylcholine (SPC) and cholesterol as independent variables and % entrapment efficiency as dependent variables for optimization of formulation variables. The optimized liposomal formulation was characterized for particle size, shape, morphology, crystallinity, zeta potential, % entrapment efficiency, residual solvent content and in vitro drug release. The process and formulation variables were optimized to achieve maximum drug entrapment efficiency and yield. Results for particle size, zeta potential, % entrapment efficiency and in vitro drug release of PEGylated liposomes were found to be 269.2 ± 2.8 nm, −27.2 ± 1.8 mV, 79.2 ± 4.4 %w/w and 37.5 ± 4.5% in 24 h, respectively. The liposomes were found to be small, unilamellar and spherical with smooth surface as seen in photomicrographs of scanning electron microscopy and transmission electron microscopy. Differential scanning calorimetry and X-ray diffraction results indicated a molecular dispersion of docetaxel in the liposomes. In this study, supercritical fluid technology was successfully used to prepare small, spherical and unilamellar liposomes of docetaxel with high entrapment. It was observed that supercritical fluid technique can be an excellent technique for preparation of docetaxel liposomes which otherwise is very difficult to prepare as a solvent free and stable liposomes.     

Encapsulation and release of cladribine from chitosan nanoparticles

This study shows the potential of chitosan (CH) nanoparticles as both an oral and IV drug delivery system using the anticancer drug cladribine as a model drug. Smooth, spherical nanoparticles were prepared by the ionotropic gelation of CH with sodium tripolyphosphate. Nanoparticle size depended on degree of hydration, drug loading, and crosslinking conditions, with the smallest nanoparticles in the size range of 212 ± 51 nm. Cladribine was entrapped in the CH matrix with an entrapment efficiency of up to 62%, depending on the initial loading. The release of cladribine followed a near‐Fickian diffusion rate over the first several hours and then reached a plateau. A second release phase began after 30–40 h of incubation in the release medium, and proceeded until ～100 h. Loaded CH nanoparticles that were crosslinked with genipin showed a delayed release profile, with only 40% of loaded drug being released after 100 h. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

A nanoparticulate raloxifene delivery system based on biodegradable carboxylated polyurethane: Design,optimization, characterization,and in vitro evaluation

Biodegradable carboxylated polyurethanes with three molecular weights were synthesized to prepare a nanoparticulate sustained delivery system of raloxifene hydrochloride, the drug with poor bioavailability. The nanoparticles were prepared by coprecipitation method. Optimal conditions for the preparation of nanoparticles were obtained using Box–Behnken design. Independent factors were ratio of polymer to drug, M_w of polymer and speed of magnetic stirrer. Dependent variables include zeta potential, polydispersity index (PdI), particle size, and loading efficacy (LE). Results of the fractional factorial design based on an analysis of variance demonstrated that the model for particle size, zeta potential, PdI and loading efficacy was statistically significant. The size of nanoparticles in design experiments were 46–96 nm in diameter and had entrapment efficiency of 84–92%. The nanoparticles were evaluated for in vitro release and showed a sustained release profile (24.19% ± 4.35% after 4 weeks), following the Fickian diffusion‐based release mechanism. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39668.     

Studies on improving the performance of rubber seed oil fuel for diesel engine with DEE port injection

Use of vegetable oils in diesel engines leads to a marginally inferior performance and higher smoke emissions due to their high viscosity and carbon residue. The performance of vegetable oils can be improved by injecting a small quantity of diethyl ether (DEE) along with air. The main objective of this study is to improve the performance, emission and combustion characteristics of a direct injection diesel engine fuelled with rubber seed oil (RSO) through DEE injection at different flow rates of 100, 150 and 200 g/h. A single cylinder diesel engine with rated output of 4.4 kW at 1500 rpm was converted to operate in the DEE injection mode. DEE was injected into the intake port during suction stroke, while rubber seed oil was injected directly inside the cylinder at the end of compression stroke. The injection timing of DEE was optimized for this mode of operation. Results indicate that the brake thermal efficiency of the engine improves from 26.5% with neat RSO to a maximum of 28.5% with DEE injection rate of 200 g/h. Smoke reduces from 6.1 to 4 BSU with DEE injection at the maximum efficiency flow rate. Hydrocarbon and carbon monoxide emissions are also less with DEE injection. There is an increase in the NO_x emission from 6.9 g/kWh to 9.3 g/kWh at the optimum DEE flow rate. DEE injection with RSO shows higher peak pressure and rate of pressure rise compared to neat RSO. Heat release rate indicates an increase in the combustion rate due to the reduced ignition delay and combustion duration with DEE injection.     

Long-term release of chlorhexidine from dental adhesive resin system using human serum albumin nanoparticles

A functional dental adhesive resin system with antimicrobial properties was developed using human serum albumin (HSA) nanoparticles as the drug delivery carrier. HSA nanoparticles loaded with chlorhexidine (CHX) diacetate, a model antimicrobial drug, were prepared using a desolvation technique. The resulting CHX-loaded HSA nanoparticles were incorporated into a commercial methyl methacrylate (MMA)-based resin. The size of the nanoparticles ranged 50–300 nm, and the nanoparticles were dispersed homogeneously in the resin matrix. The CHX-loaded HSA nanoparticles showed an early release burst of ~20 % of the total CHX by day 5, followed by the sustained release of the remaining CHX over the next 20 days. In contrast, the resin matrix containing the HSA nanoparticles showed a sustained release of CHX without an early release burst in a 4-week immersion study. In the agar diffusion test, the resin matrix incorporating the CHX-loaded HAS nanoparticles showed a larger growth inhibition zone against Streptococcus mutans than the resin matrix alone, indicating that this delivery platform potently imparts antibacterial activity to the resins. These results also suggest that CHX, which inhibits the growth of oral bacteria, can be incorporated efficiently into the MMA-based resin matrix using HSA nanoparticles.     

Preparation of poly(DL‐lactide‐co‐glycolide) nanoparticles without surfactant

The preparation of poly(DL ‐lactide‐co‐glycolide) (PLGA) nanoparticles was performed by a dialysis method without surfactant or emulsifiers. The size of the PLGA nanoparticles prepared from dimethylacetamide (DMAc) as an initial solvent was smaller than that from acetone. The sizes of the PLGA nanoparticles from DMAc and acetone were 200.4 ± 133.0 and 642.3 ± 131.1 nm, respectively. The effects of the initial solvent selected to dissolve the copolymer and the lactide:glycolide ratio were investigated. The PLGA nanoparticles were spherical as revealed by the results of scanning electron microscopy and transmission electron microscopy observations. From these results it was shown that PLGA nanoparticles could be formed by the dialysis method without surfactant. The drug‐loading contents and efficiency were also dependent on the lactide:glycolide ratio and initial feeding amount of the drug. A higher lactide ratio resulted in higher drug loading and higher loading efficiency. However, a higher initial feeding amount of the drug resulted in higher drug loading and lower loading efficiency. Clonazepam was released for at least 2 days and the release rate was slower with a higher lactide:glycolide ratio and a larger amount of drug‐loading nanoparticles than that with a lower lactide:glycolide ratio and a smaller amount of drug‐loading nanoparticles. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 2228–2236, 2001     

Formulation and statistical optimization of multiple-unit ibuprofen-loaded buoyant system using 2-factorial design

This present investigation deals with the development and optimization of buoyant beads containing ibuprofen by emulsion-gelation method for gastroretentive delivery. The effect of three independent process variables like amount of sodium alginate, magnesium stearate, and liquid paraffin on drug entrapment, density, and drug release of buoyant beads containing ibuprofen was optimized using 2³ factorial design. The observed responses were coincided well with the predicted values, given by the optimization technique. The optimized beads showed drug entrapment efficiency of 83.07 ± 3.25%, density of 0.89 ± 0.11 g/cm³, cumulative drug release of 35.02 ± 1.24% after 8 h, and floated well over 8 h in simulated gastric fluid (pH 1.2) with 4.50 min buoyant lag-time. The average size of all buoyant beads ranged from 1.43 ± 0.05 to 1.82 ± 0.14 mm. The buoyant beads were characterized by SEM and FTIR spectroscopy for surface morphology and excipients–drug interaction analysis, respectively. All these beads showed prolonged sustained release of ibuprofen over 8 h in simulated gastric fluid (pH 1.2). The ibuprofen release profile from these buoyant beads followed Korsmeyer–Peppas model over a period of 8 h with anomalous (non-Fickian) diffusion mechanism for drug release.     

Synthesis of chitosan‐graft‐β‐cyclodextrin for improving the loading and release of doxorubicin in the nanopaticles

Chitosan‐graft‐β‐cyclodextrin (CS‐g‐β‐CD) copolymer was synthesized by conjugating β‐cyclodextrins to chitosan molecules through click chemistry. The copolymer structure was characterized by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR). CS‐g‐β‐CD/CMC nanoparticles were prepared by a polyelectrolyte complexation process in aqueous solution between CS‐g‐β‐CD copolymer and carboxymethyl chitosan (CMC), which was used to load anticancer drug (Doxorubicin hydrochloride, DOX·HCl) with hydrophobic group. The particle size, surface charge, zeta potential, and morphology of the nanoparticles were characterized with dynamic light scattering. The drug loading efficiency and in vitro release of DOX·HCl of the nanoparticles were measured by ultraviolet spectrophotometer. The results demonstrated that the size, surface charge and drug loading efficiency of the nanoparticles could be modulated by the fabrication conditions. The drug loading efficiency of CS‐g‐β‐CD/CMC nanoparticles was improved from 52.7% to 88.1% because of the presence of β‐CD moieties with hydrophobic cavities, which can form inclusion complexes with the drug molecules. The in vitro release results showed that the CS‐g‐β‐CD/CMC nanoparticles released DOX·HCl in a controlled manner, importantly overcoming the initial burst effect. These nanoparticles possess much potential to be developed as anticancer drug delivery systems, especially those drugs with hydrophobic group. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41034.     

Preparation a core-shell lipid/polymer nanoparticle containing Isotretinoin drug with pH sensitive property: A response surface methodology study

In this study, a core-shell lipid/polymer nanoparticle (NP) was prepared to deliver Isotretinoin drug with pH sensitive and controllable drug release property for oral administration usage. Chitosan was cross-linked to tripolyphosphate to form the core of the NP using the ionic gelation technique and coated with glycerol monostearate lipid as a shell by applying a two-step approach. Response surface methodology was used to investigate the effects of various parameters on particle size and drug entrapment efficiency of the nanoparticles. Optimal nanoparticles with lower particle size and higher entrapment efficiency had a diameter of 100 nm based on TEM analysis and 64% drug entrapment efficiency. Coating NPs surface with lipid changed the NPs charge, hydrophilicity and swelling property. Lipid coating NPs changed release rate from 6 to 4% after 2 h in simulated gastric fluid (SGF), 9 to 16% after 6 h in simulated intestine fluid (SIF) and 21 to 71% after 7 days in blood medium. Kinetic modeling of drug release confirmed Fickian diffusion based on Higuchi model in SIF and blood media where swelling and dissolution of polymer network were negligible, while drug dissolution due to polymer swelling in SGF media was the dominant mechanism for drug release.     

Preparation and nanoencapsulation of l-asparaginase II in chitosan-tripolyphosphate nanoparticles and in vitro release study

This paper describes the production, purification, and immobilization of l-asparaginase II (ASNase II) in chitosan nanoparticles (CSNPs). ASNase II is an effective antineoplastic agent, used in the acute lymphoblastic leukemia chemotherapy. Cloned ASNase II gene (ansB) in pAED4 plasmid was transformed into Escherichia coli BL21pLysS (DE3) competent cells and expressed under optimal conditions. The lyophilized enzyme was loaded into CSNPs by ionotropic gelation method. In order to get optimal entrapment efficiency, CSNP preparation, chitosan/tripolyphosphate (CS/TPP) ratio, and protein loading were investigated. ASNase II loading into CSNPs was confirmed by Fourier transform infrared (FTIR) spectroscopy, and morphological observation was carried out by transmission electron microscopy. Three absolute CS/TPP ratios were studied. Entrapment efficiency and loading capacity increased with increasing CS and TPP concentration. The best ratio was applied for obtaining optimal ASNase II-loaded CSNPs with the highest entrapment efficiency. Size, zeta potential, entrapment efficiency, and loading capacity of the optimal ASNase II-CSNPs were 340 ± 12 nm, 21.2 ± 3 mV, 76.2% and 47.6%, respectively. The immobilized enzyme showed an increased in vitro half-life in comparison with the free enzyme. The pH and thermostability of the immobilized enzyme was comparable with the free enzyme. This study leads to a better understanding of how to prepare CSNPs, how to achieve high encapsulation efficiency for a high molecular weight protein, and how to prolong the release of protein from CSNPs. A conceptual understanding of biological responses to ASNase II-loaded CSNPs is needed for the development of novel methods of drug delivery.     

A facile synthetic strategy for Mg-Al layered double hydroxide material as nanocarrier for methotrexate

Mg-Al layered double hydroxide nanopowders were synthesised by a facile coprecipitation technique at different pH conditions. LDH nanoparticles of higher aspect ratio with an average particle size of 26 nm were obtained at pH 9 whereas a pH of 11.3 resulted in LDH nanoparticles of average size 50 nm with lower aspect ratio and narrower size distribution. LDH-MTX organo-inorganic nanohybrid was produced with an average particle size of 53 nm after intercalation of MTX into the interlayer space of LDH, as evident from the shift of (0 0 3) peak in X-ray diffraction. This was corroborated by the transmission electron micrograph, which showed an increase in average interlayer spacing from 8.00 Å in pristine LDH to 21.4 Å in LDH-MTX nanohybrid. Thermogravimetric analyses showed ∼33.2 wt% MTX loading in the LDH structure. The MTX release profile from Mg-Al LDH-MTX nanohybrid in phosphate buffer saline at pH 7.4 follows Ritger-Peppas kinetics model which demonstrates that the release kinetics is diffusion controlled. An attempt has been made to explain the above observations based on the effect of electrical double layer repulsions on the growth of LDH nuclei, primarily considering significance of the particle morphology in drug delivery application.     

New Method to Prepare Mitomycin C Loaded PLA-Nanoparticles with High Drug Entrapment Efficiency

The classical utilized double emulsion solvent diffusion technique for encapsulating water soluble Mitomycin C (MMC) in PLA nanoparticles suffers from low encapsulation efficiency because of the drug rapid partitioning to the external aqueous phase. In this paper, MMC loaded PLA nanoparticles were prepared by a new single emulsion solvent evaporation method, in which soybean phosphatidylcholine (SPC) was employed to improve the liposolubility of MMC by formation of MMC–SPC complex. Four main influential factors based on the results of a single-factor test, namely, PLA molecular weight, ratio of PLA to SPC (wt/wt) and MMC to SPC (wt/wt), volume ratio of oil phase to water phase, were evaluated using an orthogonal design with respect to drug entrapment efficiency. The drug release study was performed in pH 7.2 PBS at 37 °C with drug analysis using UV/vis spectrometer at 365 nm. MMC–PLA particles prepared by classical method were used as comparison. The formulated MMC–SPC–PLA nanoparticles under optimized condition are found to be relatively uniform in size (594 nm) with up to 94.8% of drug entrapment efficiency compared to 6.44 μm of PLA–MMC microparticles with 34.5% of drug entrapment efficiency. The release of MMC shows biphasic with an initial burst effect, followed by a cumulated drug release over 30 days is 50.17% for PLA–MMC–SPC nanoparticles, and 74.1% for PLA–MMC particles. The IR analysis of MMC–SPC complex shows that their high liposolubility may be attributed to some weak physical interaction between MMC and SPC during the formation of the complex. It is concluded that the new method is advantageous in terms of smaller size, lower size distribution, higher encapsulation yield, and longer sustained drug release in comparison to classical method.     

玉米肽-麦芽糊精糖基化产物与α-生育酚共组装纳米粒子的制备及其性质

通过美拉德反应制备玉米肽-麦芽糊精糖基化产物,再通过反溶剂法制备糖基化产物与α-生育酚共组装纳米粒子,系统地研究了制备参数对于复合粒子的影响。结果表明,糖基化产物浓度、玉米肽与α-生育酚质量比、pH对于复合粒子的粒度与ζ电位有重要的影响。采用动态光散射、ζ电位观察发现,通过调节制备参数,荷载α-生育酚的玉米肽-麦芽糊精糖基化产物可以形成平均粒度为80～100 nm的纳米粒子,其表面电荷分布在-23～-32 mV之间。与玉米肽、玉米肽/麦芽糊精混合物相比,玉米肽-麦芽糊精糖基化产物对于α-生育酚具有更高的荷载效率以及更好的pH稳定性。     

Doxorubicin‐loaded poly(butylcyanoacrylate) nanoparticles produced by emulsifier‐free emulsion polymerization

ABSTRACT: Doxorubicin‐loaded poly(butylcyanoacrylate) (PBCA) nanoparticles (NPs) were prepared by an emulsifier‐free emulsion polymerization technique. The pH values of the polymerization medium and the weight ratios of doxorubicin to butylcyanoacrylate had a significant effect on the mean particle size. The particle diameter determined by transmission electron microscopy showed that the nanoparticles were predominantly less than 50 nm. Drug loading and entrapment efficiency increased with increasing pH of the medium. The surface tension of the polymerization media increased with increasing polymerization time and reached a plateau after 4 h. Doxorubicin‐loaded PBCA NPs carried a positive charge, and the zeta potential of drug‐loaded nanoparticles increased with the increase of the polymerization pH. Molecular weight, analyzed by gel permeation chromatography, showed that the nanoparticles mainly consisted of oligomers of PBCA. The release rate of doxorubicin from nanoparticles in biological phosphate buffer was very slow, with a half‐life of 111.43 h. The results indicate that drug‐loaded nanoparticles can be prepared by an emulsifier‐free emulsion polymerization technique and that the resulting nanoparticles might be suitable for targeting drug delivery vehicles for clinical application. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 78: 517–526, 2000     

Budesonide-Loaded Guar Gum Microspheres for Colon Delivery: Preparation,Characterization and in Vitro/in Vivo Evaluation

A novel budesonide (BUD) colon delivery release system was developed by using a natural polysaccharide, guar gum. The rigidity of the microspheres was induced by a chemical cross-linking method utilizing glutaraldehyde as the cross-linker. The mean particle size of the microspheres prepared was found to be 15.21 ± 1.32 µm. The drug loading and entrapment efficiency of the formulation were 17.78% ± 2.31% and 81.6% ± 5.42%, respectively. The microspheres were spherical in shape with a smooth surface, and the size was uniform. The in vitro release profiles indicated that the release of BUD from the microspheres exhibited a sustained release behavior. The model that fitted best for BUD released from the microspheres was the Higuchi kinetic model with a correlation coefficient r = 0.9993. A similar phenomenon was also observed in a pharmacokinetic study. The prolongation of the half-life (t_1/2), enhanced residence time (mean residence time, MRT) and decreased total clearance (CL) indicated that BUD microspheres could prolong the acting time of BUD in vivo. In addition, BUD guar gum microspheres are thought to have the potential to maintain BUD concentration within target ranges for a long time, decreasing the side effects caused by concentration fluctuation, ensuring the efficiency of treatment and improving patient compliance by reducing dosing frequency. None of the severe signs, like the appearance of epithelial necrosis and the sloughing of epithelial cells, were detected.     

PLGA Biodegradable Nanoparticles Containing Perphenazine or Chlorpromazine Hydrochloride: Effect of Formulation and Release

In our study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles loaded with perphenazine (PPH) and chlorpromazine hydrochloride (CPZ-HCl) were formulated by emulsion solvent evaporation technique. The effect of various processing variables, including PLGA concentration, theoretical drug loading, poly(vinyl alcohol) (PVA) concentration and the power of sonication were assessed systematically to obtain higher encapsulation efficiency and to minimize the nanoparticles size. By the optimization formulation process, the nanoparticles were obtained in submicron size from 325.5 ± 32.4 to 374.3 ± 10.1 nm for nanoparticles loaded with PPH and CPZ-HCl, respectively. Nanoparticles observed by scanning electron microscopy (SEM) presented smooth surface and spherical shape. The encapsulation efficiency of nanoparticles loaded with PPH and CPZ-HCl were 83.9% and 71.0%, respectively. The drug loading were 51.1% and 39.4% for PPH and CPZ-HCl, respectively. Lyophilized nanoparticles with different PLGA concentration 0.8%, 1.3% and 1.6% (w/v) in formulation process were evaluated for in vitro release in phosphate buffered saline (pH = 7.4) by using dialysis bags. The release profile for both drugs have shown that the rate of PPH and CPZ-HCl release were dependent on a size and amount of drugs in the nanoparticles.     

Sustainable Stabilizer-Free Nanoparticle Formulations of Valsartan Using Eudragit® RLPO

The bioavailability of the antihypertensive drug valsartan can be enhanced by various microencapsulation methods. In the present investigation, valsartan-loaded polymeric nanoparticles were manufactured from Eudragit^® RLPO using an emulsion–solvent evaporation method. Polyvinyl alcohol (PVA) was found to be a suitable stabilizer for the nanoparticles, resulting in a monodisperse colloid system ranging in size between 148 nm and 162 nm. Additionally, a high encapsulation efficiency (96.4%) was observed. However, due to the quaternary ammonium groups of Eudragit^® RLPO, the stabilization of the dispersion could be achieved in the absence of PVA as well. The nanoparticles were reduced in size (by 22%) and exhibited similar encapsulation efficiencies (96.4%). This more cost-effective and sustainable production method reduces the use of excipients and their expected emission into the environment. The drug release from valsartan-loaded nanoparticles was evaluated in a two-stage biorelevant dissolution set-up, leading to the rapid dissolution of valsartan in a simulated intestinal medium. In silico simulations using a model validated previously indicate a potential dose reduction of 60–70% compared to existing drug products. This further reduces the expected emission of the ecotoxic compound into the environment.     

Formation of retinyl palmitate-loaded poly(l-lactide) nanoparticles using rapid expansion of supercritical solutions into liquid solvents (RESOLV)

Poly(l-lactide) (PLLA) nanoparticles loaded with retinyl palmitate (RP) were successfully prepared by rapid expansion of a supercritical carbon dioxide (CO₂) solution into an aqueous receiving solution containing a stabilizing agent (RESOLV). Three stabilizing agents, Pluronic F127, Pluronic F68, and sodium dodecyl sulfate (SDS) have been employed and the Pluronic F127 was found to be more effective for stabilizing PLLA/RP nanoparticles than Pluronic F68 and SDS, as RESOLV into a 0.1 wt% Pluronic F127 solution produced a stable nanosuspension consisting mainly of well-dispersed, individual nanoparticles. The effect of rapid expansion processing conditions (i.e., degree of saturation (S), pre-expansion temperature (T_pre), and concentrations of PLLA and RP (C_PLLA, C_RP)) on the particle size, form, and RP loading was systematically investigated. It was found that spherical PLLA/RP nanoparticles with an average size range of ∼40-110 nm and RP loadings of 0.9-6.2 wt% were consistently produced by RESOLV. The size of PLLA/RP nanoparticles increased from ∼30-80 to ∼30-160 nm as the solution degree of saturation changed from S < 1 to S > 1, independent of T_pre, C_PLLA, and C_RP. The entrapment capacity of RP in PLLA nanoparticles was predominantly determined by T_pre and C_RP. Increasing the T_pre from 70 to 100 °C and the C_RP from 0.05 to 0.15 wt% increased the encapsulated RP content at least twofold. Our results show that the technique with benign supercritical CO₂ should be generally applicable to nanoparticle fabrications of other important active ingredients, especially in liquid form, in polymeric nanoparticles.