Improved Entrapment Efficiency Research Articles

Unravelling the success of transferosomes against skin cancer: Journey so far and road ahead.

Skin cancer remains one of the most prominenttypesof cancer. Melanoma and non-melanoma skin cancer are commonly found together, with melanoma being the more deadly type. Skin cancer can be effectively treated with chemotherapy, which mostly uses smallmolecular medicines, phytoceuticals, and biomacromolecules. Topical delivery of these therapeuticsis a non-invasive way that might be useful in effectively managing skin cancer. Different skin barriers, however, presented a major obstacle to topical cargo administration. Transferosomes have demonstrated significant potential in topical delivery by improving cargo penetration through the circumvention of diverse skin barriers. Additionally, the transferosome-based gel can prolong the residence of drug on the skin, lowering the frequency of doses and their associated side effects. However, the choice of appropriate transferosome compositions, such as phospholipids and edge activators, and fabrication technique are crucial for achieving improved entrapment efficiency, penetration, and regulated particle size. The present review discusses skin cancer overview, current treatment strategies for skin cancer and their drawbacks. Topical drug deliveryagainst skin cancer is also covered, along with the difficulties associated with it and the importance of transferosomes in avoiding these difficulties. Additionally, a summary of transferosome compositions and fabrication methods is provided. Furthermore, topical delivery of small molecular drugs, phytoceuticals, and biomacromolecules using transferosomes and transferosomes-based gel in treating skin cancer is discussed. Thus, transferosomes can be a significant option in the topical delivery of drugs to manage skin cancer efficiently.

Polyvinyl pyrrolidone/starch/hydroxyapatite nanocomposite: A promising approach for controlled release of doxorubicin in cancer therapy

Doxorubicin (DOX) is an effective and widely used cancer chemotherapy drug, though its use is extremely dangerous due to side effects such as cardiotoxicity resulting from high doses. Herein, a sustainable and biocompatible starch/polyvinyl pyrrolidone/hydroxyapatite nanocomposite was prepared and loaded with DOX by water-in-oil-in water (W/O/W) emulsification method. Fourier-transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) confirmed the successful synthesis of the nanocomposite and indicated strong interactions between its components. Scanning electron microscopy (SEM) images revealed the quasi-spherical shape of the nanocomposite and dynamic light scattering (DLS) showed an average particle size of 258 nm. The zeta potential at pH 5.4 was −37.28 mV, corroborating its colloidal stability. Doxorubicin release in the ex vivo environment was investigated at pH 5.4 and 7.4, mimicking tumour and physiological conditions, respectively, and the results showed no initial burst release and a faster release kinetics in the acidic environment owed to the repulsive forces among protonated oxygenated groups of the drug and the polymers. The W/O/W improved entrapment efficiency and enabled a gradual DOX release, thus increasing the drug stability. The cell biocompatibility and anticancer activity of the drug-loaded nanocomposite were proved by MTT analysis on breast cancer fibroblast cells (7-MCF). The synthesized nanocomposite shows great potential as an effective nanocarrier of anticancer drugs for controlled release in the acidic environment of the tumour.

TPGS/soluplus® blended micelles: an effective strategy for improving loading capacity of ferroptosis inducer erastin

Erastin is the most classical small molecular ferroptosis inducer but its clinical application is hindered due to its poor solubility. Nanotechnology has been used to improve ferroptosis inducer erastin’s solubility. The recently reported erastin-incorporated nanosystems (e.g., nanoparticulate ferritin, poly(ethylene glycol) methyl ether-blockpoly(lactide-co-glycolide) (mPEG-PLGA) nanoparticle, exosome, and liposome) could to some degree elevate its solubility, but were still poor in loading capacity. To be specific, the maximum entrapment efficiency and drug loading in previous studies were approximately 36% and 3.7%, respectively. In order to improve drug loading capacity, we constructed a novel carrier based on Vitamin E d-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) blended micelles. The erastin@TPGS/Soluplus® micelles were prepared by thin film hydration method, and formulation details including dosage of Soluplus®, the weight ratio of TPGS to Soluplus®, the weight ratio of erastin to TPGS/Soluplus® were optimized. The physicochemical properties of the erastin micelles were measured by DLS, TEM, FTIR, and TG-DSC analysis. The products exhibited a nanoscale and uniform particle size (78.11 ± 0.54 nm) and neutral surface charge (-0.43 ± 0.32 mV). Significantly improved entrapment efficiency (89.63 ± 1.81%) and drug loading rate (10.03 ± 0.14%) were obtained, which was over 2-fold of current reports. The in vitro release study demonstrated that erastin could release in a sustained yet complete manner, and the drug release might be governed by multiple mechanisms including anomalous diffusion of non-Fickian diffusion, matrix erosion and sustained release. In summary, this proposed erastin nanosystem provides a new strategy for improving loading capacity, and may probably augment ferroptosis-inducing therapy for cancer treatment.

Design and Statistical Optimization of Novel Polyelectrolyte Complex Microbeads to Improve Entrapment Efficiency and Release Study of Vildagliptin.

The current research focused on the improvement of drug entrapment efficiency and release study of hydrophilic drug through polymer complextation. Ionotropic gelation technique was utilised for the preparation of Polyelectrolyte complex microbeads of Vildagliptin using Sodium alginate and Eudragit RL100 and their performance was optimized by Central composite design. Fourier Transform Infrared Spectroscopy, Scanning Electron Microscope, Differential Scanning Calorimetry, particle size, Drug Entrapment Efficiency, X-ray diffraction and in vitro drug release at 10hr were chosen for evaluating formulated microbeads. The impact of independent variables like concentration of sodium alginate and eudragit RL100 was examined over dependent responses. The interpretation of XRD, SEM, DSC, and FTIR affirmed no drug excipients interference and confirmed formation of polyelectrolyte complex microbeads. For complex microbeads, the maximum and minimum drug release after 10 hours was obtained as 96.23.5% and 89.45%, respectively. The 32 central composite design was further used to obtain response surface graph and the values for the particle size, DEE and Drug release were retained as 0.197, 76.30 % and 92.15%, respectively for the optimize batch. The result suggested the combination of two polymers (Sodium alginate and Eudragit RL100) were suitable for improving the entrapment efficiency of hydrophilic drug (Vildagliptin). The central composite design (CCD) technique is an effective tool for obtaining optimal drug delivery systems of Vildagliptin polyelectrolyte complex microbeads.

Optimisation and evaluation of Gymnema sylvestre extract loaded polymeric nanoparticles for enhancement of in vivo efficacy and reduction of toxicity

Aim This work studies the development and evaluation of Gymnema sylvestre (GYM) extract loaded sustained release polymeric nanoparticles (PNPs) for enhanced bioavailability and reduced nephrotoxicity. The current therapy is associated with the drawbacks of addiction and repeated administration. Method The sustained release PNPs were developed and evaluated for toxicity. PNPs of GYM were prepared by double emulsion solvent evaporation technique utilising Taguchi model and evaluated for physicochemical properties (particle size, zeta potential, entrapment efficiency), in vitro drug release, compatibility, and stability. Further, the bioavailability and in vivo nephrotoxicity studies in diabetic rat model were also carried out. Result The developed optimised nanoparticles were 205.7 ± 1.20 nm in size, −40.68 mV zeta potential, compatible, and stable in nature with improved entrapment efficiency (67.1 ± 0.2%) and sustained release. Moreover, nanoparticles were found to lower the blood glucose level in single as well as multiple doses. Results of in vivo study indicated that GYM-NPs increased the phosphorylase activity and thus enhanced insulin secretion. Furthermore, the nanoparticles were free from toxicity, which was confirmed by the estimation of kidney biomarker. Conclusion The nanoparticles increased the bioavailability of GYM extract and have a great potential for the treatment of diabetes in reduced dose, and so these can be potential candidates for treating diabetes.

Preparation and characterization of an elastin nanogel with enhanced biocompatibility and improved entrapment efficiency in prostate cancer cells

Nanogels represent an emerging class of drug delivery systems with enhanced renal clearance and serum half-life. However, synthetic polymeric nanogels are immunogenic and less biodegradable than other systems. Protein nanogels, being non-immunogenic; biodegradable; biocompatible; and mechanically, spatially, and temporally tunable, are gaining widespread attention. Elastin, a natural structural component of connective tissue, has enhanced vascular mobility and is highly biodegradable, biocompatible, temperature and pH sensitive, inert in the bloodstream, able to self-assemble, and able to permeate the blood-brain-barrier. In this study, the development of an Elastin Nanogel (ENG) and its functional capacity as a next generation injectable nano-drug carrier was studied. ENG was prepared via an inverse mini-emulsion technique and was characterized and found to be stable at room temperature and cytocompatible with five different prostate cancer cell lines of varied etiologies. Rhodamine-loaded ENG showed enhanced cellular uptake. Blood smear, hemolysis, CBC, PT/APTT, and C3a complement activation assays showed that ENG is vascular tissue compatible and hence meets the objectives of injectable nanogels. The formulated ENG can be efficiently used as an injectable nano-drug carrier for cancer therapy. Moreover, ENG has the potential to encapsulate hydrophobic drugs for targeted drug delivery.

Design of biopolymer carriers enriched with natural emulsifiers for improved controlled release of thyme essential oil.

This work aims to characterize a novel system for thyme essential oil delivery based on the combination of natural emulsifiers (soy protein and soy lecithin) and alginate, produced using the extrusion technique. The formulations are optimized concerning alginate and soy protein concentrations (both 1 to 1.5wt.%), and consequently lecithin amount, in order to achieve spherical beads in the range 2.0 to 2.3mm and 1.2 to 1.4mm, wet and dry, respectively. Fourier-transform infrared analysis was performed, proving that there are interactions between all components. Lecithin-soy protein synergistic combination improved entrapment efficiency of total polyphenols (for nearly 12%) and decreased thymol release in a simulated gastric solution for nearly 35%, in comparison with beads without lecithin. The addition of lecithin enhances the thermal properties of the polysaccharide-protein systems at 50 °Cafter 3 hr of heating. The mechanical stability of the biopolymer carriers is improved with lecithin addition and the elastic modulus varied from 80.06 to 123.7kPa, depending on the formulation. Alginate/soy protein/lecithin are effective carriers for the encapsulation, protection, and controlled release of thyme essential oil. PRACTICAL APPLICATION: There is unfortunately growing human resistance to antibiotics. This work offers a novel system for effective protection and controlled release of thyme essential oil in the small intestine. The mechanical and thermal properties of the carrier were estimated as they indicate how the beads will be able to resist stress during their incorporation into food (i.e. cookies-mixing, baking). The proposed approach offers ''green advantage'' as arises from all-natural materials.

Self-Assembled Lecithin/Chitosan Nanoparticles Based on Phospholipid Complex: A Feasible Strategy to Improve Entrapment Efficiency and Transdermal Delivery of Poorly Lipophilic Drug.

PurposeLecithin/chitosan nanoparticles have shown great promise in the transdermal delivery of therapeutic agents. Baicalein, a natural bioactive flavonoid, possesses multiple biological activities against dermatosis. However, its topical application is limited due to its inherently poor hydrophilicity and lipophilicity. In this study, the baicalein-phospholipid complex was prepared to enhance the lipophilicity of baicalein and then lecithin/chitosan nanoparticles loaded with the baicalein-phospholipid complex were developed to improve the transdermal retention and permeability of baicalein.MethodsLecithin/chitosan nanoparticles were prepared by the solvent-injection method and characterized in terms of particle size distribution, zeta potential, and morphology. The in vitro release, the ex vivo and in vivo permeation studies, and safety evaluation of lecithin/chitosan nanoparticles were performed to evaluate the effectiveness in enhancing transdermal retention and permeability of baicalein.ResultsThe lecithin/chitosan nanoparticles obtained by the self-assembled interaction of chitosan and lecithin not only efficiently encapsulated the drug with high entrapment efficiency (84.5%) but also provided sustained release of baicalein without initial burst release. Importantly, analysis of the permeation profile ex vivo and in vivo demonstrated that lecithin/chitosan nanoparticles prolonged the retention of baicalein in the skin and efficiently penetrated the barrier of stratum corneum without displaying skin irritation.ConclusionThese results indicate the potential of drug-phospholipid complexes in enhancing the entrapment efficiency and self-assembled lecithin/chitosan nanoparticles based on phospholipid complexes in the design of a rational transdermal delivery platform to improve the efficiency of transdermal therapy by enhancing its percutaneous retention and penetration in the skin.

Improved Drug Loading and Sustained Release of Entecavir‐loaded PLGA Microsphere Prepared by Spray Drying Technique

The purpose of this study was to construct a poly(lactic‐co‐glycolic acid) microparticle (PLGA MP) of entecavir (ETV), an anti‐viral agent for hepatitis B, for parenteral sustained delivery. To improve entrapment efficiency of the hydrophilic small compound in MPs, different fabrication methods such as double emulsion solvent evaporation and spray‐drying method were investigated. The prepared MPs were highly spherical, and the surface was smooth, irrespective of fabrication methods. On the other hand, the drug loading efficiency and in vitro release profile of ETV from the MPs were largely depending on fabrication methods. When the MPs were prepared by double emulsion method, the drug loading efficiency was extremely low (< 16.2%), with rapid drug release within two hours. On the other hand, the MPs prepared by spray‐drying process after dissolving the hydrophilic drug and PLGA polymer in acetic acid exhibited high loading efficiency more than 95%, with prolonged release profile more than 25 days. The drug release profile from the MPs prepared by spray‐drying technique was effectively adjusted by varying the lactide/glycolide ratio (75/25 or 50/50) or terminal group (carboxylic acid or ester terminated) of the biodegradable polymers. Therefore, the novel SR system fabricated by spray drying technique is expected to be an advantageous tool for the management of chronic hepatitis B with less frequent drug administration and improved patient's adherence.

An Alternative Approach for Improved Entrapment Efficiency of Hydrophilic Drug Substance in PLGA Nanoparticles by Interfacial Polymer Deposition Following Solvent Displacement

Background: Alzheimer’s disease (AD) is an age-related and irreversible neurological disorder. The low efficacy of current therapeutic strategies is related to both poor drug potency and the presence of various obstacles in the delivery routes, such as blood-brain barrier (BBB) that limits the uptake of most drugs by the brain. Rivastigmine hydrogen tartrate (RHT) is used in mild to moderate forms of AD therapy. Objectives: The present study described the use of Poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs), as effective delivery vehicles, to improve the therapeutic efficiency of RHT. Methods: RHT-loaded PLGA NPs were prepared using interfacial polymer deposition, following solvent displacement method with different ratios of polymer: Drug. The NPs were studied for entrapment efficiency, particle size, and surface morphology, using scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). In vitro drug release from NPs was also assessed by a modified dissolution method. Results: The entrapment efficiency of RHT in NPs was found to be between 27.71 ± 6.86 and 45.70 ± 11.06 and the average size was about 75.14 to 173 nm. The zeta potential was negative (-2.28 to -10.5 mV), as determined by dynamic light scattering (DLS). The drug released from NP formulations was between 69.98% and 89% upon 24 hours, which indicated improved sustained drug release characteristics. Conclusions: These results suggested the potential usefulness of PLGA NPs for the delivery of RHT in a sustained and controlled manner.

Preparation and in vitro/in vivo evaluation of PLGA microspheres containing norquetiapine for long-acting injection.

BackgroundNorquetiapine (N-desalkyl quetiapine, NQ) is an active metabolite of quetiapine with stable pharmacokinetic and pharmacological properties. However, its short half-life is a drawback for clinical applications, and long-acting formulations are required.PurposeThe objectives of this study were to prepare improved entrapment efficiency NQ freebase microspheres by the solvent evaporation method with poly(d,l-lactic-co-glycolic acid) (PLGA) as a release modulator and to evaluate their physicochemical and in vitro/in vivo release properties.MethodsNQ freebase PLGA (1:5 w/w) formulations were prepared by the oil-in-water (o/w) emulsion–solvent evaporation method. A solution of the drug and PLGA in 9:1 v/v dichloromethane:ethanol was mixed with 0.2% polyvinyl alcohol and homogenized at 2,800 rpm. The emulsion was stirred for 3 h to dilute and evaporate the solvent. After that, the resulting product was freeze-dried. Drug-loading capacity was measured by the validated RP-HPLC method. The surface morphology of the microspheres was observed by scanning electron microscopy (SEM), and the physicochemical properties were evaluated by differential scanning calorimetry, powder X-ray diffraction, and Fourier-transform infrared spectroscopy particle size distribution. The in vitro dissolution test was performed using a rotary shaking bath at 37°C, with constant shaking at 50 rpm in sink condition.ResultsThe NQ freebase microspheres prepared by o/w emulsion-solvent evaporation showed over 30% efficiency. NQ was confirmed to be amorphous in the microspheres by powder X-ray diffraction and differential scanning calorimetry. Special chemical interaction in the microspheres was not observed by FT-IR. The in vitro dissolution test demonstrated that the prepared microspheres’ release properties were maintained for more than 20 days. The in vivo test also confirmed that the particles’ long acting properties were maintained. Therefore, good in vitro–in vivo correlation was established.ConclusionIn this study, NQ freebase-PLGA microspheres showed potential for the treatment of schizophrenia for long-periods.

Tailoring the properties of mPEG-PLLA nanoparticles for better encapsulation and tuned release of the hydrophilic anticancer drug.

Gemcitabine is used as a first-line drug for treating many solid tumours. However, it suffers from a major drawback of strong side effects and short plasma half-life because of degradation by enzyme when administered intravenously. Polyesters and copolyesters are the most widely used and preferred class of biodegradable polymer. In the present work, efforts have been made to prepare poly(ethylene glycol) monomethoxy ether-poly(L-lactide) (mPEG-PLLA), a biodegradable amphiphilic copolymer with a view to improve the entrapment and tuned release of hydrophilic drug gemcitabine. The different mPEG-PLLA copolymers were synthesized with the varying ratios of mPEG and characterized by different techniques namely FTIR and 1H NMR spectroscopy, solution viscosity, differential scanning calorimetry (DSC) and gel permeation chromatography (GPC). Gemcitabine-loaded nanoparticles were prepared using mPEG-PLLA copolymers by two methods i.e. nanoprecipitation and double emulsion solvent evaporation. The nanoprecipitation method showed very less entrapment and polymer solubility in the acetone-water mixture leading to uncontrolled polymer precipitation. The difficulties encountered in the nanoprecipitation method were overcome with the help of the double emulsion (w/o/w) solvent evaporation technique. It has been observed from the results that biodegradable copolymer nanoparticles protect the drug from degradation and also help in controlling the release of encapsulated drug. The properties of nanoparticles can be tailored by varying the composition of mPEG in order to get improved entrapment efficiency and desired drug release. The nanoparticles were assessed for their in vitro cytotoxicity (MTT and FACS) and cellular uptake (fluorescence microscopy) study which showed very promising results. Nanoparticles were also studied for their in vivo release after intravenous administration to Wistar albino rats, which successfully showed controlled drug release for more than 14days.

Alginate-polyvinyl alcohol based interpenetrating polymer network for prolonged drug therapy, Optimization and in-vitro characterization

A new natural and synthetic polymeric blend to form interpenetrating polymer network (IPN) hydrogels was synthesized utilizing sodium alginate and PVA as polymers by free radical polymerization employing 2-Acylamido-2-methylpropane-sulfonic acid as monomer (AMPS) and tramadol HCl as model drug through 32 level full factorial design to evaluate the impact of selected independent factors i.e. polymer (sodium alginate) and monomer (AMPS) contents on swelling index at 18th hour, percent drug release at 18th hour, time required for 80% drug release and drug entrapment efficiency as dependent variables. FTIR, SEM, sol-gel analysis, equilibrium swelling studies and in-vitro release kinetics were performedfor in-vitro characterization of formulated IPN hydrogels. In-vitro studies carried out at pH 1.2 and pH 7.4 revealed pH independent swelling and drug release from polymeric IPN, providing controlled drug release for an extended period of time with improved entrapment efficiency, thereby concluding that this polymeric blend may be a promising system for the prolonged drug delivery.

Stability and controlled release of lutein loaded in zein nanoparticles with and without lecithin and pluronic F127 surfactants

Abstract The ability of zein nanoparticles, made with and without surfactants, to protect lutein from oxidation and to control its release was studied under various conditions. A combination of lecithin and pluronic F127 as surfactants was used to promote physicochemical stability of the nanoparticles and entrapped bioactives. Surfactant use resulted in an increased size, improved polydispersity index, decreased zeta potential, and improved entrapment efficiency. A two-phase lutein release profile was observed in phosphate-buffered saline (PBS) that consisted of an initial-burst release at 24 h, decreased in the presence of surfactants, followed by a gradual zero-order release profile for both systems. Lutein degradation followed second-order kinetics with no significant difference between nanoentrapped lutein and emulsified control. Nanoparticles stabilized with surfactants did improve chemical stability of lutein under different temperatures and in the presence of UV. Based on this data, the zein nanoparticles stabilized with surfactants proved to be able to protect lutein against chemical degradation and to slow down lutein release under PBS conditions.

Formulation and in vitro characterization of poly(dl-lactide-co-glycolide)/Eudragit RLPO or RS30D nanoparticles as an oral carrier of levofloxacin hemihydrate

The main objective of this study was to design positively charged Levofloxacin Hemihydrate (Levo-h)-loaded nanoparticles with improved entrapment efficiency and antibacterial activity. PLGA alone or in combinations with Eudragit® RLPO or RS30D with or without positively charged inducing agent; 1,2-dioleoyl-3-trimethylammonium-propane, chloride salt (DOTAP); were used for preparation of nanoparticles. Blending between PLGA and Eudragit® RLPO or RS30D with inclusion of DOTAP caused a marked increase in entrapment efficiency and switched zeta potential from negative to positive. Nanoparticle formulations; NR3 (Levo-h:PLGA:Eudragit® RLPO; 1:1:1 w/w with DOTAP) and NS3 (Levo-h:PLGA:Eudragit® RS30D; 1:1:1 w/w with DOTAP) that possess high positive zeta potential (59.3 ± 7.5 and 55.1 ± 8.2 mV, respectively) and Efficient Levo-h entrapment (89.54 ± 1.5 and 77.65 ± 1.8%, respectively) were selected for further examinations; in vitro release, physical stability and microbiological study. NR3 and NS3 showed significant sustained release of Levo-h. NR3 and NS3 exhibited good stability after storage at room temperature. Microbiological assay showed strengthened antibacterial activity of NR3 against both types of gram-negative bacteria (E. coli, Ps. aeruginosa) and of NS3 against Ps. aeruginosa compared to free Levo-h solution. NR3 and NS3 appear to be promising oral delivery system for Levo-h.

Preparation and <i>In Vitro</i> Release Study of Quaternized Chitosan Nanoparticles

In order to exploit a novel drug carrier for 5-fluorocrai (5-Fu) with improved entrapment efficiency (EE) and loading capacity (LC) determined by UV/Vis spectrophotometer, N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC) nanoparticles were prepared via the ionic gelation based on the electrostatic interactions between positively charged HTCC and negatively charged sodium tripolyphosphate (TPP). The in vitro release behavior of 5-Fu molecules encapsulated within HTCC nanoparticles took a controlled manner in PBS buffer solution (pH 7.4), initiating from a rapid release within 2 hours following a slower sustained release. A higher substitution degree of quaternary ammonium group (DQ) along HTCC chain generated a stronger electrostatic interaction between positively charged HTCC and negatively charged 5-Fu as a result of a higher positively charge density, and contributed to the controlled release of 5-Fu from HTCC nonaparticles. The formation mechanism of HTCC nanoparticles and 5-Fu-loaded HTCC nanoparticles was probed based on the results of fourier transforms infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and size and zeta potential analysis.

Polymer assisted entrapment of netilmicin in PLGA nanoparticles for sustained antibacterial activity

This study was aimed to develop poly(dl-lactide-co-glycolide) (PLGA) nanoparticle of highly water soluble antibiotic drug, netilmicin sulfate (NS) with improved entrapment efficiency (EE) and antibacterial activity. Dextran sulfate was introduced as helper polymer to form electrostatic complex with NS. Nanoparticles were prepared by double emulsification method and optimized using 25-1 fractional factorial design. EE was mainly influenced by dextran sulfate: NS charge ratio and PLGA concentration, whereas particle size (PS) was affected by all factors examined. The optimized NS-loaded-NPs had EE and PS of 93.23 ± 2.7% and 140.83 ± 2.4 nm respectively. NS-loaded-NPs effectively inhibited bacterial growth compared to free NS. Sustained release protected its inactivation and reduced the decline in its killing activity over time even in presence of bronchial cells. A MIC value of 18 μg/mL was observed for NPs on P. aeruginosa. Therefore, NPs with sustained bactericidal efficiency against P. aeruginosa may provide therapeutic benefit in chronic pulmonary infection, like cystic fibrosis.

Long chain microRNA conjugates in calcium phosphate nanoparticles for efficient formulation and delivery.

A long chain microRNA-34a conjugate (lc-miRNA) was prepared by chemical crosslinking in order to improve entrapment efficiency into calcium phosphate nanoparticles (CaPs) and intracellular delivery. Thiol-modified miRNA at both terminal ends was chemically conjugated using crosslinkers to form lc-miRNA which was encapsulated within CaPs by a conventional co-precipitation method. Encapsulation efficiencies, physicochemical properties, and in vitro intracellular delivery efficiencies of the prepared linear polyethyleneimine (LPEI)-coated CaPs (LPEI-CaP) containing common miRNA and lc-miRNA were comparatively evaluated. The prepared lc-miRNA exhibited noticeably enhanced encapsulation efficiency during the CaP formulation process when compared to common miRNA. LPEI-CaP/lc-miRNAs consisted of nano-sized particles with great homogeneity and were observed to be successfully delivered into PC-3 cells. Fabricated LPEI-CaPs with duplex form of lc-miRNA (lc-miRNA-d) suppressed cancer cell proliferation as well as migration much more efficiently than those with duplex form of miRNA (miRNA-d). In addition, LPEI-CaP/lc-miRNA-d conferred negligible cytotoxicity on PC-3 cells. Chemical crosslinking of therapeutic miRNAs via a reducible linkage may allow more efficient encapsulation within CaPs as well as homogeneous particle formulation due to a higher spatial charge density than common miRNAs. The well-formulated LPEI-CaPs with lc-miRNA-d have the potential to provide superior miRNA transfection efficiency and inhibition of cancer proliferation.

A Method to Prepare Solid Lipid Nanoparticles with Improved Entrapment Efficiency of Hydrophilic Drugs

Introduction: Premise of the present study was to suitably select or modify the constitution of the lipid matrix to achieve significantly high entrapment of hydrophilic drugs within solid lipid nanoparticles (SLNs). Methods and Materials: Isoniazid was selected as a representative hydrophilic drug with a high solubility of 230 mg/ml and a log P of -0.402 at 25°C (determined as per OECD TG 105 and 107 respectively). Three lipids/fatty acids (Glyceryl monostearate, Compritol 888 ATO® and stearic acid) were evaluated out of which Compritol 888 ATO® and stearic acid showed favorable interactions (FTIR and DSC studies) with isoniazid. The two lipids were used alone or in combination for preparing SLNs. Formulation of SLNs by microemulsification, method involved pouring the hot microemulsion into cold water under constant stirring, which may result in expulsion of the hydrophilic drug from the lipid matrix; hence, partitioning of isoniazid from the hot lipid melts into cold water was also determined. Results and Discussion: Results indicate that combining stearic acid with Compritol 888 ATO® in certain ratio (1:4) led to significant entrapment efficiency (EE) of 84.0±1.1%. The formulations were subjected to morphological, physiochemical and in vitro drug release studies. Developed SLNs were found to be stable for 1 year at 4 °C. Conclusion: The study demonstrates the benefit of excipient screening techniques in improving entrapment efficiency of a hydrophilic drug. Keywords: Solid lipid nanoparticle, isoniazid, entrapment efficiency, lipid combination, excipient selection.

Exploration of statistical experimental design to improve entrapment efficiency of acyclovir in poly (d, l) lactide nanoparticles

Objective: In current exploration, systematic attempts have been made to improve the entrapment efficiency of a model hydrophilic drug substance, i.e. acyclovir, in poly (d, l) lactide (PLA) nanoparticles (NPs) using a modified nanoprecipitation technique.Methods: Formulation parameters such as drug to polymer ratio, antisolvent selection, electrolyte (NaCl) addition, pH alteration and temperature were screened to improve the entrapment efficiency of acyclovir in PLA NPs. The temperature of the system (0–5 °C), phase volume ratio (1:2), stirring speed (2000 rpm), sonication time (5 min), etc. were kept constant during the preparation of NPs. Drug to polymer ratio and electrolyte addition emerged as critical formulation parameters affecting particle size as well as entrapment efficiency. Hence, in the present investigation a 32 full factorial design was used to investigate the combined influence of two factors, i.e. drug to polymer ratio (X1) and the amount of electrolyte, i.e. NaCl (X2) on particle size (Y1) and entrapment efficiency (Y2). The NPs were also evaluated for drug-excipient compatibility study by employing DSC and FT-IR analysis, whereas in vitro drug release studies were performed using dialysis bag technique in phosphate buffer pH 7.4.Results: Statistically significant models were evolved to predict entrapment efficiency and particle size. The effect of factors X1, X2 and was found to be statistically significant in nature. Response variables, i.e. entrapment efficiency and particle size, were simultaneously optimized using desirability function using Design Expert software. This process allowed the selection of most suitable level of factors to achieve desired level of particle size and entrapment efficiency. The results of multiple linear regression analysis revealed that for obtaining desirable particle size (less than 250 nm) and entrapment efficiency (more than 17%), the NPs should be prepared using 1:3 drug to polymer ratio and 0.04 M NaCl. Acyclovir was found to be compatible with PLA as indicated by DSC and FT-IR studies. The experimental values obtained from the optimized formulation highly agreed with the predicted values. The drug release from the optimized formulation exhibited biphasic pattern and the drug release kinetics was best explained by Weibull model.Conclusion: In conclusion, results of the present study demonstrated that PLA NPs with expected particle size and entrapment efficiency can be obtained by adopting the concept of quality by design.