Modification and stabilizing effects of PEG on resveratrol-loaded solid lipid nanoparticles

Resveratrol-loaded solid lipid nanoparticles (SLNs) modified by polyethylene glycol (PEG2000) (RES–PEG–SLNs) were prepared to study the stabilizing influences of PEG2000 on SLNs properties including loading capacity, particle size, photostability, and release. The micromorphology, particle size distribution, drug–lipid–modifier interaction and crystalline structure were characterized to elucidate stabilizing effects of PEG2000 on SLNs. Compared with ordinary SLNs, SLNs modified by PEG2000 at relatively low amounts of [m(PEG2000):m(lipids) = 1:10] exhibit high drug loading, steady nanoparticle size distributions, photostability and sustained release. According to characterizations, RES–PEG–SLNs formation is dependent on the physical interactions of drug–lipid–modifier. Since PEG2000 is doped into lipid matrix in a non-crystalline state, the lipids crystalline arrangement is disrupted. Additionally, RES–PEG–SLNs are crystallized in a PEG2000/lipid eutectic mixture rather than a simple mixture, inhibiting the lipid polymorphism transformation from α- to β-form, and therefore preventing drug exclusion from the lipid matrix. The PEG2000/lipid matrix contains lattice defects, which allow for the incorporation of more resveratrol and preventing it from photodegradation effectively. In contrast to the burst release of SLNs modified without PEG2000, resveratrol is released more slowly from the lattice defects in lipid matrix of RES–PEG–SLNs, resulting in a sustained release fitted by a two-stage exponential kinetic equation. PEG2000 is distributed on the RES–PEG–SLNs surface, increasing repulsion between nanoparticles and avoiding particles aggregation. These results confirm that both matrix doping effects and surface steric hindrance produced by the presence of PEG2000 play important roles in maintaining high loadings, nanoparticle size, photostability and sustained release.     

Tryptanthrin-loaded nanoparticles for delivery into cultured human breast cancer cells, MCF7: the effects of solid lipid/liquid lipid ratios in the inner core

Tryptanthrin is an ancient medicine which recently was also found to have a function of downregulating multidrug resistance (MDR). However, tryptanthrin is insoluble in water, which limits its availability for delivery into cancer cells. There is a need to improve delivery systems to increase the inhibition of MDR. The aim of this study was to employ nanoparticles encapsulating tryptanthrin to improve the delivery and promote the sustained release of this drug. The approach was to encapsulate tryptanthrin in various nanoparticles, including solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and lipid emulsions (LEs). We compared the particle size and zeta potential of these nanoparticles, and evaluated the partitioning behavior of tryptanthrin in them. We also determined the release kinetics of tryptanthrin from these nanoparticles. Moreover, cellular cytotoxicity toward and uptake of tryptanthrin-loaded nanoparticles by human breast cancer cells were determined. We found that the mean particle size of NLCs was lower, and the partition coefficient was higher than those of SLNs, and an increased tryptanthrin release rate was found with the NLC delivery system. NLCs achieved the sustained release of tryptanthrin without an initial burst. In particular, the NLC-C formulation, composed of a mixture of Compritol and squalene as the core materials, showed the highest release rate and cytotoxic effect. Confocal laser scanning microscopic images confirmed drug internalization into cells which enhanced the endocytosis of the particles. These results suggested that NLCs can potentially be exploited as a drug carrier for topical or intravenous use in the future.     

Preparation,Characterization, and In Vitro Release of Chloramphenicol Loaded Solid Lipid Nanoparticles

In the present contribution, solid lipid nanoparticles have been prepared from oil-in-water microemulsion, using various monoglycerides (monocaprate, monolaurate and monomyristin) as solid matrix, polyethylene glycol sorbitan monooleate (Tween 80) as emulsifier, and chloramphenicol as target drug. The morphology and microstructure of drug loaded SLNs were investigated by use of the transmission electron microscope (TEM) and x-ray diffraction (XRD) techniques. The pictures of TEM showed that SLNs are spherical particles, and the average diameters measured by dynamic light scattering (DLS) were under 100 nm. The crystallographic properties of them were characterized by XRD. It was found that chloramphenicol do not exist in crystalline state in SLN. Both drug-free and drug-loaded SLN existed in amorphous state. In addition, zeta potentials of SLNs were investigated. Zeta potentials of all the samples were around ?6 to ?23 mv. Further more, the core-shell model with drug enriched shell was proposed for the present system. Release kinetics of chloramphenicol from SLN showed a relative fast release in the initial several hours, and the release profile was accordance with the drug incorporation model we presented. Effects of types and concentration of lipids, and surface modifiers on drug release behavior were studied.     

Formulation design, preparation and physicochemical characterizations of solid lipid nanoparticles containing a hydrophobic drug: effects of process variables

This study aimed to prepare solid lipid nanoparticles (SLNs) of a hydrophobic drug, tretinoin, by emulsification-ultrasonication method. Solubility of tretinoin in the solid lipids was examined. Effects of process variables were investigated on particle size, polydispersity index (PI), zeta potential (ZP), drug encapsulation efficiency (EE), and drug loading (L) of the SLNs. Shape and surface morphology of the SLNs were investigated by cryogenic field emission scanning electron microscopy (cryo-FESEM). Complete encapsulation of drug in the nanoparticles was checked by cross-polarized light microscopy and differential scanning calorimetry (DSC). Crystallinity of the formulation was analyzed by DSC and powder X-ray diffraction (PXRD). In addition, drug release and stability studies were also performed. The results indicated that 10mg tretinoin was soluble in 0.45±0.07 g Precirol? ATO5 and 0.36±0.06 g Compritol? 888ATO, respectively. Process variables exhibited significant influence in producing SLNs. SLNs with <120 nm size, <0.2 PI, >I30I mV ZP, >75% EE, and ～0.8% L can be produced following the appropriate formulation conditions. Cryo-FESEM study showed spherical particles with smooth surface. Cross-polarized light microscopy study revealed that drug crystals in the external aqueous phase were absent when the SLNs were prepared at ≤0.05% drug concentration. DSC and PXRD studies indicated complete drug encapsulation within the nanoparticle matrix as amorphous form. The drug release study demonstrated sustained/prolonged drug release from the SLNs. Furthermore, tretinoin-loaded SLNs were stable for 3 months at 4°C. Hence, the developed SLNs can be used as drug carrier for sustained/prolonged drug release and/or to improve oral absorption/bioavailability.     

Efficient loading and delivery of ciprofloxacin by smart alginate/carboxylated graphene oxide/aminated chitosan composite microbeads: In vitro release and kinetic studies

New composite microbeads were formulated as smart pH-sensitive vehicle for efficient delivery of ciprofloxacin (CIP) drug. Herein, carboxylated graphene oxide (CGO) was successfully impregnated into alginate (Alg) microbeads, which were then coated with aminated chitosan (AmCs) layer to form core–shell Alg/CGO@AmCs composite microbeads. Diverse analysis tools comprising FTIR, TGA, XRD and SEM were employed to characterize the developed carriers, while their swelling profiles and pH-sensitivity were examined under different pHs. The results clarified that increasing CGO and AmCs concentrations in microbeads matrix greatly protected Alg microbeads from fast disintegration at colon pH and prolonged their swelling time. Moreover, about 94.65 % of CIP drug was successfully loaded by Alg/CGO@AmCs composite microbeads compared to 61.95 % for Alg microbeads, confirming their reduced porosity. The in vitro CIP-release profiles were investigated in simulated gastrointestinal conditions. Furthermore, increasing AmCs concentration in the outer shell of composite microbeads clearly minimized the CIP burst release at the colon region and offered a sustained release performance. Besides, the CIP release mechanism was well-described by korsmeyer-peppas kinetic model. The cytotoxicity study confirmed the potential safety of the Alg/CGO@AmCs composite microbeads with human cell viability reached 98.98 %, suggesting their applicability as smart carriers for oral delivery of antibiotics.     

Synthesis and characterization of chitosan–polyvinylpyrrolidone–bovine serum albumin-coated magnetic iron oxide nanoparticles as potential carrier for delivery of tamoxifen

The proposed study examined the preparation of chitosan (CS)–polyvinylpyrrolidone (PVP)–bovine serum albumin (BSA)-coated magnetic iron oxide (Fe₃O₄) nanoparticles (Fe₃O₄–CS–PVP–BSA) to use as potential drug delivery carriers for delivery of tamoxifen drug (TAM) . The anticancer drug selected in this study was tamoxifen which can be used for the human breast cancer treatment. These prepared nanoparticles were characterized by FTIR, XRD, SEM, AFM, TEM, CD and VSM techniques. The swelling studies have been measured at different (10, 20, 30, 40, 50%) drug loading. The mean particle size of the tamoxifen-loaded nanoparticles system (Fe₃O₄–CS–TAM, Fe₃O₄–CS–TAM–PVP and Fe₃O₄–CS–TAM–PVP–BSA) as measured by Malvern Zetasizer ranged between 350 ± 2.3 and 601 ± 1.7 nm. As well as these drug-loaded nanoparticles were positively charged. The zeta potential was in the range of 28.9 ± 3.5 and 50.8 ± 3.9 mV. The encapsulation efficiency was between 63.60 ± 2.11 and 96.45 ± 2.12%. Furthermore, in vitro release and drug loading efficiency from the nanoparticles were investigated. The cytotoxicity of prepared nanoparticles was verified by MTT assay. In vitro release studies were executed in 4.0 and 7.4 pH media to simulate the intestinal and gastric conditions and different temperature (37 and 42 °C). Hence, the prepared tamoxifen-loaded nanoparticles system (Fe₃O₄–CS–TAM, Fe₃O₄–CS–TAM–PVP and Fe₃O₄–CS–TAM–PVP–BSA) could be a promising candidate in cancer therapy.     

Factors affecting drug encapsulation and stability of lipid-polymer hybrid nanoparticles

Lipid-polymer hybrid nanoparticles are polymeric nanoparticles enveloped by lipid layers that combine the highly biocompatible nature of lipids with the structural integrity afforded by polymeric nanoparticles. Recognizing them as attractive drug delivery vehicles, antibiotics are encapsulated in the present work into hybrid nanoparticles intended for lung biofilm infection therapy. Modified emulsification-solvent-evaporation methods using lipid as surfactant are employed to prepare the hybrid nanoparticles. Biodegradable poly (lactic-co-glycolic acid) and phosphatidylcholine are used as the polymer and lipid models, respectively. Three fluoroquinolone antibiotics (i.e. levofloxacin, ciprofloxacin, and ofloxacin), which vary in their ionicity, lipophilicity, and aqueous solubility, are used. The hybrid nanoparticles are examined in terms of their drug encapsulation efficiency, drug loading, stability, and in vitro drug release profile. Compared to polymeric nanoparticles prepared using non-lipid surfactants, hybrid nanoparticles in general are larger and exhibit higher drug loading, except for the ciprofloxacin-encapsulated nanoparticles. Hybrid nanoparticles, however, are unstable in salt solutions, but the stability can be conferred by adding TPGS into the formulation. Drug-lipid ionic interactions and drug lipophilicity play important roles in the hybrid nanoparticle preparation. First, interactions between oppositely charged lipid and antibiotic (i.e. ciprofloxacin) during preparation cause failed nanoparticle formation. Charge reversal of the lipid facilitated by adding counterionic surfactants (e.g. stearylamine) must be performed before drug encapsulation can take place. Second, drug loading and the release profile are strongly influenced by drug lipophilicity, where more lipophilic drug (i.e. levofloxacin) exhibit a higher drug loading and a sustained release profile attributed to the interaction with the lipid coat.     

Preparation of gamma cyclodextrin stabilized solid lipid nanoparticles (SLNS) using stearic acid–γ-cyclodextrin inclusion complex

The inclusion complexation behaviour of higher chain fatty acid, stearic acid (SA) with gamma cyclodextrin has been investigated. The inclusion complex was characterized by FT-IR, ¹H NMR, 2D NMR, XRD and DSC techniques. The results showed that the SA molecule was entrapped inside the gamma cyclodextrin cavity. Further, inclusion complex was treated with lopinavir at 85 °C and emulsified with hot water at 85 °C. The resulted nanoemulsion was cooled down to form solid lipid nanoparticles (SLNs) stabilized with gamma cyclodextrin. Prepared SLNs were having average particle size of 212.5 ± 4.8 nm, zeta potential of ?19.7 ± 0.66 mV and drug loading of 57.54 ± 0.62 %. The surface characteristics of SLNs were also observed with transmission electron microscopy and atomic force microscopy. Results indicate that inclusion complex of SA and gamma cyclodextrin can be used for SLNs preparation.     

Lymphatic targeting of hematoporphyrin monomethyl ether using poly (butyl-cyanoacrylate) based nanoparticle drug delivery system

The traditional treatment has inevitable drawbacks of nonspecific lymph targeting, poor therapeutic efficiency and residual metastatic for advanced cancer patients with lymph node metastases. To overcome these shortcomings, we prepare a nano-carrier drug delivery system. Photosensitizer hematoporphyrin monomethyl ether (HMME)-loaded poly (n-butylcyanoacrylate) nanoparticles (PBCA-NPs) was prepared successfully. The particle size was approximately 160 nm, the envelopment rate was 87.9%, and the drug loading rate was about 13.4%. The drug release study in vitro showed that the cumulative release rates of HMME-PBCA-NPs group was much less than free HMME group. The drug distribution in different tissues showed that the peak-reach time was 3 h in free HMME group and 6 h in nanoparticles group. All of these results confirmed the slow release characteristic of nanoparticles. In lymph node tissues, the HMME concentrations in HMME-PBCA-NPs group were much higher than those of the free HMME group at any time points we tested, in which the maximum difference concentration of HMME appeared at 6 h (1.2884?±?0.04695 vs. 0.0438?±?0.00558 µg/mg) after drug delivery. The mesenteric lymph nodes of rabbits were enlarged obviously in the NP group than in free HMME group at 6 h after drug delivery. All of these results confirmed the slow release characteristic and the lymphatic targeting characteristic of nanoparticles. In summary, we developed a lymphatic targeting nanoparticles drug delivery system successfully, which showed perfect lymph targeting and has the potential to be a new therapy strategy for advanced cancer patients with lymph node metastasis.     

Acyclovir-Loaded Chitosan Microspheres for Gastroretention: Development and Evaluation

Mucoadhesive chitosan microspheres of acyclovir were prepared to prolong the gastric residence time using simple emulsification phase separation technique. The particle morphology of drug-loaded formulations was measured by SEM and the particle size distribution was determined using an optical microscope. The release profile of acyclovir from microspheres was examined in simulated gastric fluid (SGF pH 1.2). The particles were found to be discreet and spherical with the maximum particles of an average size (31.62 ± 4.64). The entrapment efficiency was found to be in the range of 40.24 to 67.29%. The concentration of the glutaraldehyde (25%v/v) as a cross-linker 2 ml and drug polymer ratio of 1:2 caused an increase in the entrapment efficiency and the extent of drug release. The optimized chitosan microspheres were found to possess good bioadhesion (79.89 ± 1.01%). The gamma-scintigraphy study showed the gastric residence time of more than 6 hours which revealed that optimized formulation could be a good choice for gastroretentive systems.     

The enhancement on thermal stability and charring–forming capability of nitration group

Lipid nanoparticles, both solid lipid nanoparticles and nanostructured lipid carriers (NLC), containing tacrolimus (FK) were obtained by solvent diffusion method associated with ultrasonication using stearic acid (SA) or beeswax as solid lipid. The oleic acid was used as liquid lipid in the NLC. Lipid nanoparticles were characterized by determining the drug loading, particle size, polydispersity index (PDI) and zeta potential (ZP). Analysis by differential scanning calorimetry and X-ray diffraction were performed. Lipid nanoparticles presented nano-sized from 139 to 275 nm. The PDI results show the particles present from 0.3 to 0.5, and ZP was higher than |25| mV. Drug loading ranged of 2.3–3.2%. SA nanoparticles presented better ZP, average size and distribution. However, beeswax nanoparticles showed higher drug loading. Results suggest there are no incompatibilities between FK and the raw materials. Polymorphic modifications were not observed. The results presented show that lipid nanoparticles using both lipids were successfully obtained and may represent promising delivery system of FK in topical formulations.     

Core–shell nanoparticles of carboxy methyl cellulose and compritol-PEG for antiretroviral drug delivery

Multi-functional nanoparticles hold great promise for the effective treatment of many diseases. Zidovudine a commonly used anti-HIV drug, requires a delivery system for more effective treatment of AIDS. The present study focuses on the development of anti-viral drug-loaded hybrid nanoparticles (LPNs) of lipid and polymer consisting of carboxy methyl cellulose—zidovudine (AZT) core enclosed by a compritol (Comp)-polyethylene glycol shell. The characterization of drug loaded LPNs was done using TEM, DLS and FT-IR analysis. The drug loading efficiency, drug release, blood compatibility, MTT assay and cell uptake studies were carried out using the LPNs. The synthesized nanoparticles exhibited core–shell morphology with an average size of 161.65 ± 44.06 nm; the LPN also demonstrated 82% drug encapsulation efficiency with slow drug release behaviour. The hybrid nanoparticles were found to be blood compatible and non toxic. The rhodamine-labeled hybrid nanoparticles were also found to effectively enter the brain cells. The novel hybrid drug delivery system shows controlled drug release, biocompatibility and high drug loading efficiency. These LPNs obtained from natural polymers can provide an excellent platform for designing systems for targeted drug delivery.     

Design and Characterization of Maltoheptaose-b-Polystyrene Nanoparticles,as a Potential New Nanocarrier for Oral Delivery of Tamoxifen

Tamoxifen citrate (TMC), a non-steroidal antiestrogen drug used for the treatment of breast cancer, was loaded in a block copolymer of maltoheptaose-b-polystyrene (MH-b-PS) nanoparticles, a potential drug delivery system to optimize oral chemotherapy. The nanoparticles were obtained from self-assembly of MH-b-PS using the standard and reverse nanoprecipitation methods. The MH-b-PS@TMC nanoparticles were characterized by their physicochemical properties, morphology, drug loading and encapsulation efficiency, and release kinetic profile in simulated intestinal fluid (pH 7.4). Finally, their cytotoxicity towards the human breast carcinoma MCF-7 cell line was assessed. The standard nanoprecipitation method proved to be more efficient than reverse nanoprecipitation to produce nanoparticles with small size and narrow particle size distribution. Moreover, tamoxifen-loaded nanoparticles displayed spherical morphology, a positive zeta potential and high drug content (238.6 ± 6.8 µg mL⁻¹) and encapsulation efficiency (80.9 ± 0.4 %). In vitro drug release kinetics showed a burst release at early time points, followed by a sustained release profile controlled by diffusion. MH-b-PS@TMC nanoparticles showed higher cytotoxicity towards MCF-7 cells than free tamoxifen citrate, confirming their effectiveness as a delivery system for administration of lipophilic anticancer drugs.     

Quick synthesis of lipid-polymer hybrid nanoparticles with low polydispersity using a single-step sonication method

Lipid-polymer hybrid nanoparticle, consisting of a hydrophobic polymeric core and a lipid monolayer shell, represents a new and promising drug delivery platform that has shown controllable particle size and surface functionality, high drug loading yield, sustained drug release profile, and excellent in vitro and in vivo stability. These lipid monolayer-coated polymeric nanoparticles are typically fabricated through a modified nanoprecipitation method, which involves sample heating, vortexing, and solvent evaporation. Herein we report a new and fast method to synthesize lipid-polymer hybrid nanoparticles with controllable and nearly uniform particle size. Using a bath sonication approach, we demonstrate that the whole hybrid nanoparticle synthesis process can be completed in about 5 min compared with a few hours for previous synthesis approaches. The size and polydispersity of the resulting nanoparticles can be readily controlled by tuning the relative concentrations of individual building components. Colloidal stability tests of the synthesized hybrid nanoparticles in PBS buffer and serum show no signs of aggregation over a period of 5 days. The present method improves the production rate of the hybrid nanoparticles by near 20-fold while not compromising the physicochemical properties of the particles. This work may facilitate the bench-to-bedside translation of lipid-polymer hybrid nanoparticles as a robust drug nanocarrier by allowing for fabricating a large amount of these nanoparticles at high production rate.     

Stimuli‐responsive zein‐based nanoparticles as a potential carrier for ellipticine: Synthesis,release, and in vitro delivery

In the present research, we have investigated a drug delivery system based on the pH‐responsive behaviors of zein colloidal nanoparticles coated with sodium caseinate (SC) and poly ethylene imine (PEI). These systematically designed nanoparticles were used as nanocarriers for encapsulation of ellipticine (EPT), as an anticancer drug. SC and PEI coatings were applied through electrostatic adsorption, leading to the increased size and improved polydispersity index of nanoparticles as well as sustained release of drug. Physicochemical characteristics such as hydrodynamic diameter, size distribution, zeta potential and morphology of nanoparticles prepared using different formulations and conditions were also determined. Based on the results, EPT was encapsulated into the prepared nanoparticles with a high drug loading capacity (5.06%) and encapsulation efficiency (94.8%) under optimal conditions. in vitro experiments demonstrated that the release of EPT from zein‐based nanoparticles was pH sensitive. When the pH level decreased from 7.4 to 5.5, the rate of drug release was considerably enhanced. The mechanism of pH‐responsive complexation in the drug encapsulation and release processes was extensively investigated. The pH‐dependent electrostatic interactions and drug state were hypothesized to affect the release profiles. Compared to the EPT‐loaded zein/PEI nanoparticles, the EPT‐loaded zein/SC nanoparticles exhibited a better drug sustained‐release profile, with a smaller initial burst release and longer release period. According to the results of in vitro cytotoxicity experiments, drug‐free nanoparticles were associated with a negligible cytotoxicity, whereas the EPT‐loaded nanoparticles displayed a high toxicity for the cancer cell line, A549. Our findings indicate that these pH‐sensitive protein‐based nanoparticles can be used as novel nanotherapeutic tools and potential antineoplastic drug carriers for cancer chemotherapy with controlled release.     

Surface modification of cellulose nanocrystal with chitosan oligosaccharide for drug delivery applications

A novel drug delivery system based on two of the most abundant natural biopolymers was developed by modifying the surface of oxidized cellulose nanocrystal (CNC) with chitosan oligosaccharide (CS_OS). First, the primary alcohol moieties of CNC were selectively oxidized to carboxyl groups using the 2,2,6,6-tetramethylpiperidine-1-oxyl radical catalyst. The amino groups of CS_OS were then reacted with carboxylic acid groups on oxidized CNC (CNC-OX) via the carbodiimide reaction using N-hydroxysuccinimide and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide as coupling agents. Successful grafting of CS_OS to CNC-OX was confirmed by infrared spectroscopy, thermogravimetry, potentiometric titration, and zeta potential measurements. The grafting resulted in a conversion of ~90 % carboxyl groups on CNC-OX and the degree of substitution was 0.26. CNC–CS_OS nanoparticles showed a binding efficiency of 21.5 % and a drug loading of 14 % w/w. A drug selective electrode was used to directly measure the concentration of procaine hydrochloride released from CNC–CS_OS particles. The in vitro drug release was studied at pH 8 and the nanoparticles revealed a fast release of up to 1 h, which can be used as biocompatible and biodegradable drug carriers for transdermal delivery applications.     

Biocompatible APTES–PEG Modified Magnetite Nanoparticles: Effective Carriers of Antineoplastic Agents to Ovarian Cancer

Magnetite nanoparticles are particularly attractive for drug delivery applications because of their size-dependent superparamagnetism, low toxicity, and biocompatibility with cells and tissues. Surface modification of iron oxide nanoparticles with biocompatible polymers is potentially beneficial to prepare biodegradable nanocomposite-based drug delivery agents for in vivo and in vitro applications. In the present study, the bare (10 nm) and polyethylene glycol (PEG)–(3-aminopropyl)triethoxysilane (APTES) (PA) modified (17 nm) superparamagnetic iron oxide nanoparticles (SPIO NPs) were synthesized by coprecipitation method. The anticancer drugs, doxorubicin (DOX) and paclitaxel (PTX), were separately encapsulated into the synthesized polymeric nanocomposites for localized targeting of human ovarian cancer in vitro. Surface morphology analysis by scanning electron microscopy showed a slight increase in particle size (27?±?0.7 and 30?±?0.45 nm) with drug loading capacities of 70 and 61.5 % and release capabilities of 90 and 93 % for the DOX- and PTX-AP-SPIO NPs, respectively (p?<?0.001). Ten milligrams/milliliter DOX- and PTX-loaded AP-SPIO NPs caused a significant amount of cytotoxicity and downregulation of antiapoptotic proteins, as compared with same amounts of free drugs (p?<?0.001). In vivo antiproliferative effect of present formulation on immunodeficient female Balb/c mice showed ovarian tumor shrinkage from 2,920 to 143 mm³ after 40 days. The present formulation of APTES–PEG-SPIO-based nanocomposite system of targeted drug delivery proved to be effective enough in order to treat deadly solid tumor of ovarian cancer in vitro and in vivo.     

Preparation,optimization by 2<Superscript>3</Superscript> factorial design,characterization and in vitro release kinetics of lorazepam loaded PLGA nanoparticles

The aim of this work was to formulate the lorazepam loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles by optimization of different preparation variables using 2³ factorial design. The effect of three independent factors, the amount of polymer, concentration of the stabilizer and volume of organic solvent was investigated on two dependent responses, i.e., particle size and % drug entrapment efficiency. By using PLGA as polymer, PVA as a stabilizer and dimethyl sulfoxide as organic solvent lorazepam loaded PLGA nanoparticles were successfully developed through modified nanoprecipitation method. FTIR and DSC studies were carried out to examine the interaction between the excipients used and to explore the nature of the drug, the formulation and the nature of drug in the formulations. These nanoparticles were characterized for particle size, shape, zeta potential, % drug entrapment efficiency, % process yield and in vitro drug release behavior. In vitro evaluation showed particles size between 161.0 ± 5.4 and 231.9 ± 4.9 nm, % drug entrapment efficiency of formulations was in the range of 60.43 ± 5.8 to 75.40 ± 1.5, % process yield at 68.34 ± 2.3 to 81.55 ± 1.3 was achieved and in vitro drug release for these formulations was in the range of 49.2 to 54.6%. Different kinetics models, such as zero order, first order, Higuchi model, Hixson-Crowell model and Korsmeyer- Peppas model were used to analyze the in vitro drug release data. Preferred formulation showed particle size of 161.0 ± 5.4 nm, PDI as 0.367 ± 0.014,–25.2 mV zeta potential, drug entrapment efficiency as 64.58 ± 3.6% and 72.48 ± 2.5% process yield. TEM results showed that these nanoparticles were spherical in shape, and follow the Korsmeyer-Peppas model with a release exponent value of n = 0.658.     

Solid lipid nanoparticles comprising internal Compritol 888 ATO, tripalmitin and cacao butter for encapsulating and releasing stavudine, delavirdine and saquinavir

Solid lipid nanoparticles (SLNs) with complex internal phase were fabricated for formulating stavudine (D4T), delavirdine (DLV), and saquinavir (SQV). The lipids including Compritol 888 ATO, tripalmitin, and cacao butter were stabilized by L-α-phospatidylcholine, cholesteryl hemisuccinate, and taurocholate to form SLNs. The results revealed that the morphology of SLNs was spheroidal with shallow surface pits. An increase in the weight percentage of Compritol 888 ATO increased the average diameter of D4T-entrapping SLNs and decreased that of DLV- and SQV-entrapping SLNs. Preservation at 4°C over 6 weeks slightly enhanced the size of SLNs. For a specific drug, an increase in the entrapment efficiency enlarged the nanocarriers. The order of drug in the average particle diameter and in the entrapment efficiency was SQV>DLV>D4T, in general. In addition, the dissolution of the three drugs from SLNs showed the characteristics of sustained release. The order of drug in the cumulative release percentage was D4T>DLV>SQV. SLNs containing Compritol 888 ATO, tripalmitin, and cacao butter are efficient in carrying antiretroviral agents for medicinal application.     

Design and In Vitro Evaluation of Solid-Lipid Nanoparticle Drug Delivery for Aceclofenac

Solid-lipid nanoparticles (SLNs) are an interesting nanoparticulate delivery system. The present work was carried out with the aim to develop a prolonged release solid-lipid nanoparticulate system for the drug using aceclofenac. Aceclofenac-loaded solid-lipid nanoparticles (ACSLNs) was prepared by hot high pressure homogenization technique. Tripalmitin was used as the lipid core. Surfactants (Poloxamer 188, Tween 80, and soya lecithin) and co-surfactant (sodium tauro glycholate) were used in the formulations. The prepared ACSLN formulations were characterized for encapsulation efficiency (EE), photon correlation spectroscopy (PCS), scanning electron microscopy (SEM), and x-ray diffraction (XRD). From these studies, mean particle diameter of the formulation prepared with combination of surfactants (Poloxmer 188 and Tween 80) was about 200 nm with spherical morphology and amorphous nature. Higher EE was obtained with SLNs prepared using combination of soya lecithin and poloxmer 188. The organization and distribution of the ingredients in the nanoparticulate system were studied by differential scanning calorimetry (DSC) and the results showed that the drug is incorporated into the solid matrix. The prepared formulations demonstrated favorable in vitro prolonged release characteristics. Experimental in vitro release data were substituted in available mathematical models to establish the release kinetics of ACSLNs and it was found to follow first-order kinetics and Higuchi diffusion mechanism. Our results suggest that these SLN formulations could constitute a promising approach for the drug delivery of aceclofenac.