High Drug Entrapment Research Articles

Sorafenib-Loaded Long-Circulating Nanoliposomes for Liver Cancer Therapy.

A type of sorafenib- (SOR-) loaded long-circulating nanoliposome was constructed, and the targeting performance and antitumor effects of the prepared liposome were evaluated in the present study. Polyethylene glycol- (PEG-) modified long-circulating nanoliposomes (LC-NPs) were designed and prepared using reverse evaporation, and the LC-NPs were used for delivering sorafenib (LC-PEG-SOR-NPs). Then, the anti-VEGFR antibody as a targeting moiety was chemically coupled with LC-PEG-SOR-NPs to form liver cancer-targeted nanoliposomes (anti-VEGFR-LC-PEG-SOR-NPs). The drug entrapment and loading efficiency were measured. And the cancer-targeting performance and therapeutic efficiency were evaluated both in vitro and in vivo. The anti-VEGFR-LC-PEG-SOR-NPs with an average of 119.8 ± 4.2 nm showed a uniform spherical structure. The drug entrapment and loading efficiency were 92.5% and 18.5%, respectively. The killing efficiency of anti-VEGFR-LC-PEG-SOR-NPs was up to 18% after incubating with liver cancer cells for 72 h. Furthermore, the anti-VEGFR-LC-PEG-SOR-NPs could actively target at the tumor region and could efficiently inhibit tumor growth with negligible side effects. This newly designed nanoliposomes had desirable dispersibility, high drug entrapment efficiency, tumor targeting and therapeutic efficiency, and good safety. As a biocompatible nanocomposite, it was promising to become a novel and useful tumor-targeting nanodrug for liver cancer therapy.

Formulation optimization and in vitro characterization of rifampicin and ceftriaxone dual drug loaded niosomes with high energy probe sonication technique

The aim of the present study was to prepare niosomal formulations for dual drug therapy of ceftriaxone sodium and poorly water-soluble rifampicin by the ecological probe sonication method. Pluronic L121 and Span 60 were used as surface active agents and the optimization of the composition was made with the aid of Design of Experiment (DoE) concept. Concentration levels of charge inducing agent, dicetylphosphate (DCP), and Pluronic L121 were studied as variables. Prepared niosomes with varying concentrations of DCP and Pluronic L121 resulted in small sized niosomes with sizes ranging from 165 nm to 893 nm. During the four weeks stability testing, the particle sizes of the empty niosomes were reduced, while the particle sizes of the drug loaded niosomes were increased very slightly. The optimized formulations resulted in stable niosomes with high drug entrapment efficiencies: entrapment efficiency was 99% for rifampicin and 96% for ceftriaxone. All the niosomal formulations showed faster in vitro drug release rates as compared to bulk drug formulations. In conclusion, ceftriaxone and rifampicin loaded niosomes prepared with Pluronic L121 and Span 60 resulted in stable, small sized niosomes with high drug entrapment efficiencies and improved drug release profiles.

Encapsulation of berberine into liquid crystalline nanoparticles to enhance its solubility and anticancer activity in MCF7 human breast cancer cells

Berberine, an isoquinoline alkaloid derived from Berberis vulgaris and plants of the Ranunculaceae family, elicits a broad range of pharmacological effects, including anticancer properties. However, poor solubility and low bioavailability limit its therapeutic use. In this study, we developed lyotropic liquid crystalline nanoparticles (LCNs) to enhance the solubility of berberine. LCNs were prepared by the ultrasonication method using monoolein, poloxamer 407, polyethylene glycol-400, and Transcutol® HP. The nanoparticles were characterized for size, surface charge, in vitro release, cytotoxicity, and cellular uptake. The average particle size ranged from 186 to 190 nm with cubical shape, and the polydispersity index was lower than 0.2. The zeta potential ranged between −9.3 and −21.9 mV with high drug entrapment efficiency (≥73.8%). The cell viability assay in MCF7 human breast cancer cells revealed that formulations prepared with polyethylene glycol-400 and Transcutol® HP exhibited significantly lower half-maximal inhibitory concentration compared with pure berberine. In cellular uptake assay, berberine concentration in Caco-2 cells was higher for LCNs prepared with Transcutol® HP. In conclusion, LCNs could be a potential carrier for enhancing the solubility and thus improving the anticancer effect of berberine against breast cancer.

Development of mebendazole loaded nanostructured lipid carriers for lymphatic targeting: Optimization, characterization, in-vitro and in-vivo evaluation

The basic objective of research work was to develop, optimize and evaluate MBZ loaded NLCs to overcome the issues of poor solubility and bioavailability of the drug. The nanoformulation was prepared by melt-emulsification ultrasonication technique and optimizes the formulation parameters by Box–Behnken design. The optimized MBZ loaded NLCs were evaluated for its particle size, drug content and encapsulation efficiency. Characterization was done by DSC, XRD, and TEM. Further, in-vitro release study, stability study, and in-vivo pharmacokinetics and biodistribution studies were also performed. The optimized MBZ loaded NLCs composed of using Compritol 888 ATO, Miglyol 812 and Poloxamer 407 as a solid lipid, liquid lipid, and surfactant respectively. The particle size, zeta potential, drug loading and entrapment efficiency of optimized NLCs were found to be 117.4 nm, −25.3 mV, 90.1% and 3.17% respectively. In-vitro drug release studies show biphasic release pattern from NLCs. Stability study indicated that the optimized nanoformulation was significantly stable at refrigerator temperature as compared to room temperature. Lymphatic uptake of the drug was achieved by prepared nanoformulation. It was concluded from the data obtained that MBZ loaded NLCs could be regarded as a potential carrier for sustained delivery of MBZ and efficient carrier for lymphatic targeting. Highlights MBZ loaded NLCs showed high drug entrapment efficiency and bioavailability. Box–Behnken design was used to optimize the formulation parameters. In-vitro release showed the biphasic sustained behavior from nanoformulation. Lymphatic uptake of MBZ through nanoformulation was observed. Improved pharmacokinetic and biodistribution were observed.

Letrozole-loaded nonionic surfactant vesicles prepared via a slurry-based proniosome technology: Formulation development and characterization

Slurry-based Letrozole (LTZ)-loaded proniosomes were designed using sucrose or sorbitol as carriers and various ratios of cholesterol (CH) and Tween 80 (T80) as lipid composition. Proniosomes were hydrated and probe-sonicated to generate nano-vesicles. The proniosome powders were characterized in terms of morphology using scanning electron microscopy, and drug crystallinity using differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The niosomes generated from proniosomes were characterized and compared to conventional niosomes, in terms of size, zeta potential, drug entrapment, storage stability, and drug release. All formulations had size measurements in the range of 100–194 nm, polydispersity index (PDI) values below 0.3, and zeta potential values below – 23 mV. Drug entrapment was the highest for niosomes generated from sucrose-based proniosomes (CH:T80; 1:1), reaching 74% compared to less than 50% for conventional niosomes. Storage for 3 months at 4 °C resulted in minor drug leakage whilst most drug was leaked from vesicles stored at room temperature. DSC and XRD studies showed that LTZ was converted into its amorphous form upon incorporation into proniosomes. Drug release exhibited a biphasic pattern, being fast at the first 24 h (up to 65% released) followed by a very slow release phase for a duration of one month, releasing at least 95%. The release profile of niosomes fits best with the Higuchi model. Overall, in this study, a facile approach to generating niosomes incorporating LTZ using a slurry-based proniosome technology was demonstrated. The niosomes provided high drug entrapment and controlled biphasic release over one month.

Chitosan-sodium Alginate Nanoparticle as a Promising Approach for Oral Delivery of Rosuvastatin Calcium: Formulation, Optimization and In vitro Characterization

Rosuvastatin calcium is the most effective antilipidemic drug and is called "super-statin" but it exhibits low aqueous solubility and poor oral bioavailability of about 20%. The present work aimed to develop and optimize chitosan-alginate nanoparticulate formulation of rosuvastatin which can improve its solubility, dissolution and therapeutic efficacy. Chitosan-alginate nanoparticles were prepared by ionotropic pre-gelation of an alginate core followed by chitosan polyelectrolyte complexation and optimization was done in terms of two biopolymers, crosslinker concentrations. The chitosan-alginate nanoparticles were characterized by various techniques such as particle properties such as size; size distribution (polydispersity index); Zeta-potential measurements and Fourier transform infrared spectra respectively. The designed rosuvastatin loaded chitosan-alginate nanoparticle had the average particle size of 349.3 nm with the zeta potential of +29.1 mV, and had high drug loading and entrapment efficiencies. Fourier transform infrared spectra showed no chemical interaction between the rosuvastatin and chitosan-alginate nanoparticle upon the encapsulation of rosuvastatin within the nanoparticles. Nanoparticles revealed a fast release during the first two hours followed by a more gradual drug release during a 24 h period. Hence, our studies demonstrated that the new chitosan-alginate nanoparticle system of rosuvastatin is a promising strategy for improving solubility and in turn, the therapeutic efficacy of rosuvastatin. Therefore, the rosuvastatin-loaded chitosan-alginate nanoparticles are a promising approach for the oral delivery of rosuvastatin.

PREPARATION, CHARACTERIZATION AND STABILITY STUDIES OF SOLID SELF EMULSIFYING DRUG DELIVERY SYSTEM OF NIFEDIPINE

Objective: The objective of this work was to improve the solubility and dissolution rate of Nifedipine by preparing a solid-self micro emulsifying drug delivery system (Solid-smedds).
 Methods: Liquid-self-emulsifying drug delivery system formulations were prepared by using linseed oil as oil, tween 80 as a surfactant and PEG 400 as cosurfactant. Components were selected by solubility screening studies and the self-emulsifying region was identified by the pseudo-ternary phase diagram. Thermodynamic stability study was performed for the determination of stable liquid-smedds formulation. These formulations were evaluated for self-emulsification time, drug content analysis, robustness to dilution test, particle size analysis, in vitro diffusion study, and Stability study. Solid self-micro emulsifying formulations were prepared by using aerosil-200 at a different ratio. Lf9S (0.65:1) was selected due to its highest drug entrapment efficiency and a decrease in particle size. It was selected for further studies into DSC, SEM, FTIR, and XRD analysis.
 Results: DSC and XRD result shows that the drug within the formulation was in the amorphous state. From the SEM study, it was observed that the drug has been uniformly distributed and having a smooth surface. From the in vitro dissolution study, it improved the dissolution rate of nifedipine which was 98.70% of drug release where pure drug release only 6.72%.
 Conclusion: In conclusion, a solid self-micro emulsifying drug delivery system is improved the solubility and drug release rate but also improved the stability of the formulation.

Decreasing acute toxicity and suppressing colorectal carcinoma using Sorafenib-loaded nanoparticles

Objective: A polymer-based nanoparticle was constructed to target sorafenib delivery to colorectal carcinoma cells and decrease the side effects of the drug.Methods: Sorafenib-loaded nanoparticles (S-NPs) based on PEG-PLGA were prepared using a double emulsion solvent evaporation method. The properties of S-NPs were evaluated and then their effects on the viability of colorectal cancer cells and normal human cells were assessed. The mechanism of S-NP internalization was explored using cellular uptake assays and in vitro fluorescence confocal imaging. Acute toxicity of sorafenib on its own or within S-NPs was assessed in mice.Results: S-NPs showed high drug loading and entrapment efficiencies, they did not cause extensive hemolysis, and they efficiently inhibited growth of colorectal cancer cell lines and human umbilical vein endothelial cells. S-NPs showed lower acute toxicity than the free drug.Conclusions: Loading sorafenib into nanoparticles can enhance its uptake by colorectal cancer cells and decrease its acute toxicity.

Enhanced oral bioavailability and hepatoprotective activity of thymoquinone in the form of phospholipidic nano-constructs

ABSTRACTBackground: The poor biopharmaceutical properties of thymoquinone (TQ) obstruct its development as a hepatoprotective agent. To surmount the delivery challenges of TQ, phospholipid nanoconstructs (PNCs) were constructed.Method: PNCs were constructed employing microemulsification technique and systematic optimization by three-factor three level Box-Behnken design.Result: Optimized PNC composition exhibited nano size (<100 nm), spherical morphology, within acceptable range of polydispersity index (0.55), high drug entrapment efficiency (>90%), controlled drug release pattern, and neutral surface charge (zeta potential of −0.65 mV). After oral administration of a single dose of PNC, it showed a relative bioavailability of 386.03% vis-à-vis plain TQ suspension. Further, TQ-loaded PNC demonstrated significant enhanced hepato-protective effect vis-à-vis pure TQ suspension and silymarin, as evidenced by reduction in the ALP, ALT, AST, bilirubin, and albumin level and ratified by histopathological analysis.Conclusion: TQ-loaded PNCs can be efficient nano-platforms for the management of hepatic disorders and promising drug delivery systems to enhance oral bioavailability of this hydrophobic molecule.

Stimuli Responsive In Situ Gelling Systems Loaded with PLGA Nanoparticles of Moxifloxacin Hydrochloride for Effective Treatment of Periodontitis

The objectives of the present research work were systematic development of novel in situ gel formulation containing nanoparticles for localised delivery of moxifloxacin against bacterial periodontitis. PLGA nanoparticles were prepared and optimised in a systematic manner. Factor screening was performed with the help of half-factorial design to identify the influential factors, while response surface optimisation of the nanoparticles was conducted using central composite design. The optimum nanoparticle formulation was chosen on the basis of lower particle size, higher drug entrapment and controlled drug release characteristics up to 1week time period, while the optimum in situ gel was selected on the basis of faster gelling and higher viscosity and gel strength properties for improved retention in the periodontium. In vivo histopathological studies and in vivo gamma scintigraphy studies revealed the extended release, superior efficacy and enhanced retention of nanoparticle-loaded in situ gelling system. Results obtained from in vivo histopathological studies after 1week treatment with in situ gel formulation containing nanoparticles of moxifloxacin were found to be better than with 3weeks treatment of marketed gel formulation. Overall, the studies ratify successful development of an effective site-specific drug delivery system with enhanced biopharmaceutical attributes for the periodontitis treatment.

Formulation and Characterization of Transethosomes for Enhanced Transdermal Delivery of Propranolol Hydrochloride

Objective: The objective of the present work was to develop transethosomes loaded with propranolol hydrochloride using Lipoid S100 as phospholipid, and oleic acid as permeation enhancer and evaluate them for prolonged release effect, in-vitro skin permeation, and in-vivo plasma concentration. Methods: Transethosomes loaded with propranolol hydrochloride were prepared by homogenization method. Furthermore, they were characterized by using Transmission Electron Microscopy (TEM), zeta sizer, Differential Scanning Calorimetry (DSC), and Confocal Laser Scanning Microscopy (CLSM) for in-vitro skin permeation. Plasma concentration profile of transethosomal gel was determined using Sprague Dawley rats and compared with a marketed oral tablet of propranolol hydrochloride. Results: Developed transethosomes loaded with propranolol hydrochloride showed acceptable size (182.7 ± 5.4 nm), high drug entrapment (81.98 ± 2.9%) and good colloidal characteristics [polydispersity index (PDI) = 0.234 ± 0.039, zeta potential = -21.91 ± 0.65 mV]. Transethosomes showed prolonged in-vitro release of propranolol hydrochloride for 24 h. Results of in-vitro skin permeation studies of transethosomal gel showed 74.34 ± 2.33% permeation of propranolol hydrochloride after 24 h and confocal microscopy revealed accumulation of transethosomes in the stratum basale layer of the skin. Transethosomal gel was capable to prolong the in-vivo release of propranolol hydrochloride upto 24 h. The value of peak plasma concentration (Cmax) of propranolol hydrochloride was found to be 93.8 ± 3.6 ng/mL which was very high compared to the marketed oral tablet of propranolol hydrochloride (45.6 ± 3.1 ng/mL). Conclusion: The results suggested that transethosomal gel of propranolol hydrochloride could be a better alternative to oral propranolol hydrochloride as it can avoid various disadvantages of oral propranolol hydrochloride like high dosing frequency, first pass effect, and organ toxicity.

Nanonet-nano fiber electrospun mesh of PCL-chitosan for controlled and extended release of diclofenac sodium.

Electrospun nanofiber (EN) technology has been used in the past to generate electrostatically charged multilayer-nanofibers. This platform offers versatile applications including in tissue engineering, drug delivery, wound dressings, and high-efficiency particulate air filters. In this study, we synthesized for the first time nanonet-nanofiber electrospun meshes (NNEMs) of polycaprolactone (PCL)-chitosan (CH) using EN technology. The fabricated NNEMs were utilized for high payload delivery and controlled release of a water-soluble drug. Diclofenac Sodium (DS), a hydrophilic anti-inflammatory drug, was selected as a model drug because of its high aqueous solubility and poor compatibility with insoluble polymers. Various compositions of DS drug-loaded NNEMs (DS-NNEMs) were synthesized. The physicochemical properties such as structure, morphology, and aqueous stability and the chemical properties of DS-NNEMs were evaluated. High drug entrapment efficiency and concentration-dependent drug release patterns were investigated for up to 14 days. Furthermore, the biocompatibility of the DS-NNEMs was tested with NIH 3T3 cells. The physicochemical characterization results showed that the DS drug is a key contributing factor in the generation of nanonet-nanofiber networks during electrospinning. DS-NNEMs also enhanced 3T3 cell adhesion, viability, and proliferation in the nanonet-nano fiber network through the controlled release of DS. The presented EN technology-based biodegradable NNEM material is not only limited for the controlled release of hydrophilic anti-inflammatory drugs, but also can be a suitable platform for loading and release of antiviral drugs.

AlCl&lt;sub&gt;3&lt;/sub&gt; Cross-Linked and Spray Dried Carboxymethyl Sago Cellulose Microspheres as Potential Carriers for the Enteric Delivery

A semisynthetic polymer of carboxymethyl sago cellulose (CMSC) was synthesized from Malaysian sago biomass and further used in the development of drug delivery system. Recently, we have reported spray-dried carboxymethyl sago cellulose (CMSC) microspheres for enteric release and dissolution enhancement of piroxicam. In the present investigation, an attempt has been made to improve the enteric release property of CMSC microspheres using aluminium chloride as a cross-linker in the spray drying process and prednisolone as a model drug. CMSC microspheres loaded with prednisolone were prepared using a cross-linker concentration of 0%, 0.01%, 0.025% and 0.05%. All the drug-loaded microspheres were found to have high drug entrapment efficiencies (DEE) ranging from 99% to 106.1%. FT-IR spectroscopy has confirmed the cross-linking in CMSC microspheres as well as intact and amorphous nature of the entrapped drug. Field Emission Scanning Electron Microscope (FESEM) results have shown agglomeration of microspheres and the presence of drugs on the surface. Cross-linked microspheres have shown better efficiency than the uncross-linked microspheres in restricting drug release in stomach pH. Only about 5% of the loaded drug was released from cross-linked microspheres at pH 1.2 while 10% of the drug was released from uncross-linked microspheres. Also, cross-linked microspheres have exhibited faster drug release in pH 6.8 than the uncross-linked microspheres. Spray-dried and AlCl3 cross-linked CMSC microspheres have shown promising results in enteric drug delivery as well as dissolution enhancement.

Retinoic acid-loaded solid lipid nanoparticles surrounded by chitosan film support diabetic wound healing in in vivo study

Repair of tissue damaged in diabetic wounds is essential to minimize the cases of amputation of the limbs in millions of diabetic people around the world. Although the all-trans retinoic acid (ATRA) is described as a potential wound healing agent, however its effects are controversial due to adverse reactions that may impair the wound healing during the treatment schedules. Our aim was to design and characterize an ATRA-loaded solid lipid nanoparticles surrounded by chitosan film to promote an ATRA controlled release and to evaluate its effectiveness in promoting wound healing in a diabetic mouse model. The SLN-ATRA were developed using biocompatible lipids without using organic solvent. The SLN-ATRA had high drug entrapment efficiency (98.0 %) and low polydispersity index (PDI) and average diameter, respectively, 0.24 ± 0.02 and 83.0 ± 6 nm. The transmission electron microscope (TEM) image presented that the SLN-ATRA were homogeneous in size and had spherical structures. The incorporation of SLN-ATRA in the chitosan films propitiated a homogeneous distribution of the drug and a controlled drug release. Furthermore, in vivo assay proved that chitosan films containing SLN-ATRA accelerated the closure of wounds of diabetic mice when compared to the control chitosan films without ATRA. SLN-ATRA chitosan films also reduced leukocyte infiltrate in the wound bed, improved collagen deposition, and reduced scar tissue. No sign of skin irritation was observed. These results indicated that SLN-ATRA surrounded in chitosan films are a promising candidate to treat diabetic wounds, improving tissue healing.

Trastuzumab-conjugated nanoparticles composed of poly(butylene adipate-co-butylene terephthalate) prepared by electrospraying technique for targeted delivery of docetaxel.

Human epidermal growth factor receptor 2 (HER-2) is overexpressed in 20-30% of human breast cancers, associated with poor prognosis and tumour aggression. The aim of this study was the production of trastuzumab-targeted Ecoflex nanoparticles (NPs) loaded with docetaxel and in vitro evaluation of their cytotoxicity and cellular uptake. The NPs were manufactured by electrospraying and characterised regarding size, zeta potential, drug loading, and release behaviour. Then their cytotoxicity was evaluated by MTT assay against an HER-2-positive cell line, BT-474, and an HER-2-negative cell line, MDA-MB-468. The cellular uptake was studied by flow cytometry and fluorescent microscope. The particle size of NPs was in an appropriate range, with relatively high drug entrapment and acceptable release efficiency. The results showed no cytotoxicity for the polymer, but the significant increment of cytotoxicity was observed by treatment with docetaxel-loaded NPs in both HER-2-positive and HER-2-negative cell lines, in comparison with the free drug. The trastuzumab-targeted NPs also significantly enhanced cytotoxicity against BT-474 cells, compared with non-targeted NPs.

Polymeric Microsphere Formulation for Colon Targeted Delivery of 5-Fluorouracil Using Biocompatible Natural Gum Katira.

Controlled release delivery system of chemotherapeutic agents at the site of colon endorses modern drug-entrapped delivery tools, which release the entrappedagents at a controlled rate for anextended period providing patient compliance and additional protection from the degradinggastric environment. Thus, the present study was aimed to develop and optimize a novel polymeric microsphere of 5-fluorouracil (5-FU) using natural gum katira to obtain an optimal therapeutic response at the colon. Due course of experimentation, in-vivo safety profile of the gum katira in an animal model was established. Modified solvent extraction/evaporation technique wasemployed to encapsulate 5-FU in the natural polymeric microsphere and was characterized using in-vitro studies to investigate particle size, morphology, encapsulation efficiency and release of the drug from developed formulation. Formulated and optimized polymeric microsphere of 5-FU using gum katira polymer own optimal physicochemical characteristics with a fine spherical particle with size ranged from 210.37±7.50 to 314.45±7.80 µm.Targeted microsphere exhibited good cytotoxicity and also has high drug entrapment efficiency, and satisfactory release pattern of the drug within a time frame of 12 h. Finally, we foresee that the optimized polymeric gum katiramicrosphere of 5-FU could be a promising micro-carrier for efficient colon drug targeting delivery tool with improved chemotherapeutic efficacy against colon cancer.

Development and Evaluation of Amoxicillin Loaded Carbopol 934P Mucoadhesive Microcapsules for Sustained Drug Release for H. pylori Treatment

Amoxicillin (α-amino-p-hydroxybenzyl-penicillin) is a semi-synthetic, orally absorbed and widely prescribed β-lactam antibiotic. It is now widely used for eradication of gastric Helicobacter pylori infection combined with a second antibiotic and an acid‐suppressing agent despite its short elimination half-life of one hour. The purpose of this study was to develop and evaluate amoxicillin loaded carbopol 934P mucoadhesive microcapsules for sustained drug release at the gastric mucosa to prolong the residence time of dosage form in the stomach and to achieve controlled drug release for more effective H. pylori eradication. Amoxicillin mucoadhesive microcapsules were formulated by ion gelation technique using 32 factorial designs. A 32 full factorial design was used to derive the statistical equation, ANOVA analysis, contour plots and 3D response surface plots. FT- IR (4000 cm-1- 450 cm-1) analysis of amoxicillin and with polymers was performed by using potassium bromide pellet method. Different polymer ratios of carbopol 934P and sodium alginate were used to formulate by nine formulations (F1 to F9) amoxicillin mucoadhesive microcapsules. The prepared formulations were characterized by determining their percentage of yield, particle size, percentage of entrapment efficiency, swelling index, percentage of mucoadhesion and percentage of drug release. Amoxicillin and used polymers are found to be compatible with no interaction reported by FTIR analysis. The optimized formulation (F9) exhibited a high drug entrapment efficiency of 96.04±0.03%, particle size of 847.2518±0.06 μm, yield of 98.86±0.01%, swelling index of 120.09±0.06%, and mucoadhesion of 67.00±0.02 after 8 h. A successful sustained drug release was achieved for more than 14 h. In-vitro dissolution test for optimized formulation (F9) demonstrated a slower release behavior in 0.1N hydrochloric acid followed by linear release profile in pH 7.4 phosphate buffer. The drug-to-polymer-to-polymer ratio had a more significant effect on the dependent variables. The release kinetic study of optimized formulation (F9) displayed a good fitting with zero order behavior and Korsmeyer-Peppas model has confirmed a non-Fickian release. The developed mucoadhesive amoxicillin microcapsules were observed to have adhered strongly with gastric mucosa with approximately 14 h of prolonged stay expecting improved bioavailability and reduced dosing frequency and subsequently improving patient’s compliance. The concentration of carbopol 934P and sodium alginate had highly significant effects on depended variables. The present study concludes that amoxicillin mucoadhesive microcapsules can be effectively used for the more effective treatment of H. pylori infection.

Anticancer activity of polymeric nanoparticles containing linoleic acid-SN38 (LA-SN38) conjugate in a murine model of colorectal cancer

Biodegradable polymeric nanoparticles (NPs) have been used frequently as nanocarriers for anticancer drugs. Linoleic acid conjugated SN38 (LA-SN38)-loaded NPs (EBNPs) were developed using biodegradable poly (ethylene oxide)-poly (butylene oxide) (PEO-PBO) diblock copolymer by titration hydration method without using a toxic organic solvent. The EBNPs had high drug loading efficiency and entrapment efficiency for LA-SN38, at 7.53% and 93.55%, respectively. The polydispersity index (PDI) and average diameter were 0.173 ± 0.019 and 226.1 ± 1.2 nm, respectively. The transmission electron microscope (TEM) image presented that the NPs were homogeneous in size and had spherical structures. In vitro study showed the release behavior of EBNPs was slow and sustained. Furthermore, cytotoxicity and apoptosis assay proved that EBNPs were more effective in growth inhibition of human colon cancer cells. Cell uptake experiments further demonstrated that EBNPs could avoid the phagocytosis by macrophages and promote the uptake by cancer cells. In vivo, EBNPs had prolonged blood circulation time and tumor selectivity in biodistribution. The tumor inhibitory rate of EBNPs was higher compared to SNPs group and CPT-11group (P < 0.01), and the drug did not show significant systemic toxicity at the tested dose. These results indicated that EBNPs are a promising candidate for delivery of LA-SN38 to treat colorectal cancer.

Intranasal dolutegravir sodium loaded nanoparticles of hydroxypropyl-beta-cyclodextrin for brain delivery in Neuro-AIDS

Dolutegravir sodium (DTG) loaded nanoparticles (NPs) were prepared by cross-linking Hydroxypropyl-β-cyclodextrin (HPβCD) with diphenyl carbonate to enhance its CNS uptake via intranasal delivery. NPs were characterized for various parameters like size, drug loading, in vitro release, safety and CNS uptake and optimized using quadratic response surface methodology (RSM) employing 2-factor, 5-level circumscribed central composite design. The batch of NPs containing DTG:HPβCD; 1:4.16 was considered optimum as uniform small NPs (size; 81±3 nm, PDI 0.378 ± 0.04) with high drug loading (14.9 ± 1.4%) and entrapment efficiency (77 ± 3.35%). NPs produced sustained drug release (89.51 ± 0.56% in 6 h) by Fickian diffusion mechanism, they provided 2.54 folds greater permeability of DTG compared to free drug and were non-toxic to L929 cell line. Significantly higher concentration of DTG in the CSF (24.89±4.56μg/mL) and higher CSF:Plasma ratio(1.64) was achieved from intranasal NPs as compared to the reported DTG concentration in the CSF (18 ng/mL) and CSF:Plasma ratio (0.11–0.66) following oral administration of tablet. High brain drug transport percentage (83.47%) from intranasal NPs confirms nose to brain transport of the drug. Gamma scintigraphy studies in rats revealed enhanced CNS uptake of drug from NPs. These results suggest that the present investigation hold promise for management of Neuro-AIDS.

Omega-3 Fatty Acid Based Nanolipid Formulation of Atorvastatin for Treating Hyperlipidemia.

Purpose: In the current study, attempts have been made to formulate an omega-3 fatty acid based nanostructured lipid carriers of atorvastatin (AT), for treating hyperlipidemia; and to evaluate their antihyperlipidemic activity using in vitro and in vivo studies. Methods: Omega-3 fatty acid based AT-loaded nanolipid carriers (NLC) were formulated by the melt emulsification ultrasonication technology. The prepared NLC consist of stearic acid (as solid lipid), omega-3 fatty acid (as liquid lipid), Tween 80, poloxamer 188 (surfactants) and soya-lecithin (co-surfactant). Results: AT loaded NLCs have a particle size of 74.76 ± 4.266 nm, a zeta potential value of -36.03 ± 1.504 mV and a high drug entrapment efficiency (EE) of 86.70 % ± 0.155. The release of AT from NLCs exhibited a sustained behaviour, which made it an ideal vehicle for drug delivery. MTT assay results indicated that NLCs are compatible with L929 (mouse fibroblast) cell lines. Anti-hyperlipidemic study showed a significant reduction in LDL and TG levels in serum with the orally administered Omega-3 fatty acid based AT loaded NLCs when compared to marketed formulation. Conclusion: The results demonstrated that the omega-3 fatty acid based NLC has the potential to be a promising nanomedicine for the treatment of hyperlipidemia.