Site-specific Delivery Systems Research Articles

Characterization and optimization of colon specific nanosponges immobilized polymeric microbeads formulation for the combined delivery of 5-fluorouracil and curcumin

Introductionand purpose: Site-specific delivery systems are highly advantageous for local cancer treatment as they allow a more significant delivery of the drug to the tumor with minimal systemic side effects. Furthermore, combination therapy is a promising approach that attracts more attention in cancer treatment due to its synergistic effects. In this work, nanosponges immobilized polymeric microbeads for colon-specific delivery systems were developed for a drug combination of 5-fluorouracil and curcumin to treat colorectal cancer. MethodsSodium alginate and low molecular chitosan polymers were used to create microbead-based formulations containing curcumin-encapsulated nanosponges and 5-fluorouracil. To improve curcumin's low solubility, Diphynylacarbonate (DPC) hyper cross-linking of β-CD was used to create curcumin-loaded β-CD nanosponges that further incorporated in the polymeric microbeads along with free 5-fluorouracil. ResultsThe optimized microbeads were spherical with a mean particle size of 1.1 ± 0.05 mm. The produced beads were subsequently coated with a multilayer coating of ethyl cellulose and Eudragit S100 polymers, which functioned as pH-dependent and time-dependent coatings to ensure drug delivery to the colon. The developed formulation (Coated MB5) showed controlled release of the drug and sustained cytotoxic effect. The release profiles of 5-fluorouracil and curcumin from Coated MB5 were best described by zero-order followed by first-order release functions. About 66.4 % of 5-FU and 73.1 % of curcumin were released for 24 h. In vivo roentgenographic evaluation in a rabbit model indicated that the optimized coated microbeads successfully reached the colon 7–9 h after administration. ConclusionsAs a prospective colon-specific drug delivery system, a successful formulation (Coated MB5) was developed for the combined delivery of 5-fluorouracil and curcumin. More in vivo studies are needed to demonstrate the therapeutic efficacy of optimized formulations and their potential to improve colorectal cancer therapy by providing a more targeted administration of combination medicines with fewer undesirable side effects.

Nanoparticle delivery systems of functional substances for precision nutrition.

Foodborne functional substances have received much attention for their functional benefits in health and disease. However, these substances are easily affected by the adverse environment during production, transportation, or storage. They will also be damaged by the gastric environment and limited by the mucosal barrier after entering the human body, thus affecting the bioavailability of functional substances in the body. The construction of nanoparticle delivery systems is helpful to protect the biological activity of functional substances and improve their solubility, stability, and absorption of substances. Responsive delivery systems help control the release of functional substances in specific environments and targeted sites to achieve nutritional intervention, disease prevention, and treatment. In this chapter, the main types of foodborne functional substances and their commonly used delivery systems were reviewed, and the application of delivery systems in precision nutrition was described from the aspects of environmental stimuli-responsive delivery systems, site-specific delivery systems, and disease-targeted delivery systems.

Homogalacturonan enriched pectin based hydrogel enhances 6-gingerol's colitis alleviation effect via NF-κB/NLRP3 axis

A nanolipidcarrier (NLC) loaded homogalacturonan enriched pectin (citrus modified pectin, MCP4) hydrogel was designed as a novel colon inflammation site-specific oral delivery system for 6-gingerol (6G) (6G-NLC/MCP4 hydrogel) administration, and its colitis alleviation effect were investigated. 6G-NLC/MCP4 exhibited typical “cage-like” ultrastructure with 6G-NLC embedded in the hydrogel matrix as observed by cryoscanning electron microscope. And due to the homogalacturonan (HG) domain in MCP4 specifically combined with Galectin-3, which is overexpressed in the inflammatory region, the 6G-NLC/MCP4 hydrogel targeted to severe inflammatory region. Meanwhile, the prolonged-release characteristics of 6G-NLC provided sustained release of 6G in severe inflammatory regions. The matrix of hydrogel MCP4 and 6G achieved synergistic alleviation effects for colitis through NF-κB/NLRP3 axis. Specifically, 6G mainly regulated the NF-κB inflammatory pathway and inhibited the activity of NLRP3 protein, while MCP4 regulated the expression of Galectin-3 and peripheral clock gene Rev-Erbα/β to prevent the activation of inflammasome NLRP3.

Cetuximab-conjugated PLGA nanoparticles as a prospective targeting therapeutics for non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is one of the most prevalent cancers diagnosed worldwide, yet managing it is still challenging. The epidermal growth factor receptor (EGFR) exhibits aberrant signalling in a wide range of human cancers, and it is reported to overexpress in most NSCLC cases. The monoclonal antibody [Cetuximab (Cet)] was conjugated onto the surface of the poly (lactide-co-glycolide) (PLGA) nanoparticles which were loaded with docetaxel (DTX) for the development of targeted therapy against lung cancer. This site-specific delivery system exhibited an enhanced cellular uptake in lung cancer cells which overexpress EGFR (A549 and NCI-H23). The nanoparticles also showed better therapeutic effectiveness against NSCLC cells, as evidenced by reduced IC50 values, cell cycle arrest at the G2/M phase, and increased apoptosis. The improved efficacy and in vivo tolerance of Cet-DTX NPs were demonstrated in benzo(a)pyrene (BaP)-induced lung cancer mice model. Histopathological analysis showed that intravenous injection of Cet-DTX NP to mice carrying lung cancer greatly reduced tumour development and proliferation. Comparing Cet-DTX NP to free drug and unconjugated nanoparticles, it also had negligible side effects and improved survival rates. Therefore, Cet-DTX NPs present a promising active targeting carrier for lung tumour-NSCLC-selective treatment.

Abstract 2005: FSHR-mediated targeted delivery of paclitaxel immunoliposomes in receptor overexpressing ovarian cancer cells

Abstract The purpose of this study was to explore the Fabʹ fragment of anti-FSHR (Follicle Stimulating Hormone Receptor) antibody as a targeting ligand to graft on the surface of paclitaxel (PTX) liposomes (PLs) for site-specific drug delivery in ovarian cancer (OC) cells. Anti-FSHR antibody Fab’ fragment conjugated PTX encapsulated immunoliposomes (ILs) were prepared, characterized, and evaluated to determine their in vitro efficacy in FSHR receptor positive (Caov3) and negative (SKOV3) OC cells. FSHR expression was determined by confocal microscopy and flow cytometry. The results confirmed that FSHR expression levels of Caov3 were higher and no expression was detected in SKOV3. ILs were prepared by covalent conjugation of Fab’ fragments to functionalized PLs via thioether linkage which was confirmed by SDS-PAGE analysis. Immunoreactivity of the prepared ILs was determined against Fabʹ in Caov3 cells using flow cytometry and it was observed that after conjugation, Fabʹ remained intact and also maintained the binding characteristic to the receptor. In MTT assay at the end of 48 h, the IC50 value for ILs was found to be 10.8 and 3.5 folds lower than Taxol® and PLs respectively in Caov3. However, being receptor negative, there was no significant difference noticed for IC50 when PLs and ILs were compared for SKOV3. To prove, whether immune tagging improves cell-specific uptake of ILs in FSHR-expressing cells, cell uptake studies were carried out using confocal microscopy and flow cytometry which showed higher uptake of ILs in Caov3 but not in SKOV3. For assessment of anti-angiogenic activity, a wound scratch assay was performed on Caov3 cells. At an equimolar concentration of treatment given to the cells by PLs and ILs, the % recovery of the wound was 1.3 and 2.3 times lower than Taxol® respectively indicating the superior performance of ILs in inhibiting cell proliferation. The quantitation of cell death after treatment was carried out by flow cytometry after staining with propidium iodide and the highest amount of cell death was seen in ILs group for Caov3 cells. Evaluation of cell cycle in the Caov3 indicated superior results of arrest of cells in G2/M phase. Further, an increase in cell death was observed as indicated by the increase in % of cells in subG1 stage. Performance of PLs was similar in Caov3 and SKOV3 leading to almost around 22% of arrest in G2/M stage, however, for ILs, the number of cells in G2/M was 28% for Caov3 cells at the end of 24 h indicating that the targeted formulation was able to better get internalized in the cells due to receptor-mediated uptake. The results highlight the importance of FSHR as a prominent target for OC therapy and the potential of anti-FSHR Antibody Fab' conjugated nanocarriers as a site-specific delivery system to reduce the limitations associated with OC chemotherapy. Citation Format: Priyanka Bhatt. FSHR-mediated targeted delivery of paclitaxel immunoliposomes in receptor overexpressing ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2005.

Abciximab coated albumin nanoparticles of rutin for improved and targeted antithrombotic effect

In this work, we fabricated rutin (RTN)-loaded albumin nanoparticles (RTN-ALB-NPs) and abciximab (ABX) coated RTN-loaded albumin nanoparticles (ABX-RTN-ALB-NPs) for the targeted prevention and treatment of thrombosis. The prepared albumin nanoparticles were of 130–200 nm in particle size range with smooth and spherical surface morphology. The entrapment efficiency was achieved up to 73.08% with an in-vitro release rate of 34.49% in the first 4 h and 85.99% by the end of 72 h. The degree of ABX conjugation on the nanoparticle surface about 62% which was further confirmed by X-ray photoelectron spectroscopy analysis, energy-dispersive X-ray spectroscopy analysis and Bradford assay. The serum stability and biocompatibility study demonstrated that the antithrombotic property of RTN was maintained, indicative of good serum stability and hemocompatibility. Moreover, the in-vitro targeting efficiency study showed approximately 10 to 20-fold much higher intracellular fluorescence intensities of targeted formulation than non-targeted formulation towards the activated platelets. The in-vitro platelet aggregation assay and blood clot assay also revealed that the inhibition of thrombus formation was significantly higher when treated with ABX-RTN-ALB-NPs than RTN-ALB-NPs. The findings showed that the developed nanoformulation is a potential site-specific delivery system of RTN for targeted prevention and treatment of thrombosis.

IAEA Contribution to Nanosized Targeted Radiopharmaceuticals for Drug Delivery.

The rapidly growing interest in the application of nanoscience in the future design of radiopharmaceuticals and the development of nanosized radiopharmaceuticals in the late 2000′s, resulted in the creation of a Coordinated Research Project (CRP) by the International Atomic Energy Agency (IAEA) in 2014. This CRP entitled ‘Nanosized delivery systems for radiopharmaceuticals’ involved a team of expert scientist from various member states. This team of scientists worked on a number of cutting-edge areas of nanoscience with a focus on developing well-defined, highly effective and site-specific delivery systems of radiopharmaceuticals. Specifically, focus areas of various teams of scientists comprised of the development of nanoparticles (NPs) based on metals, polymers, and gels, and their conjugation/encapsulation or decoration with various tumor avid ligands such as peptides, folates, and small molecule phytochemicals. The research and development efforts also comprised of developing optimum radiolabeling methods of various nano vectors using diagnostic and therapeutic radionuclides including Tc-99m, Ga-68, Lu-177 and Au-198. Concerted efforts of teams of scientists within this CRP has resulted in the development of various protocols and guidelines on delivery systems of nanoradiopharmaceuticals, training of numerous graduate students/post-doctoral fellows and publications in peer reviewed journals while establishing numerous productive scientific networks in various participating member states. Some of the innovative nanoconstructs were chosen for further preclinical applications—all aimed at ultimate clinical translation for treating human cancer patients. This review article summarizes outcomes of this major international scientific endeavor.

Synthesis of Novel Conjugated Linoleic Acid (CLA)-Coated Superparamagnetic Iron Oxide Nanoparticles (SPIONs) for the Delivery of Paclitaxel with Enhanced In Vitro Anti-Proliferative Activity on A549 Lung Cancer Cells.

The application of Superparamagnetic Iron Oxide Nanoparticles (SPIONs) as a nanomedicine for Non-Small Cell Lung Carcinoma (NSCLC) can provide effective delivery of anticancer drugs with minimal side-effects. SPIONs have the flexibility to be modified to achieve enhanced oading of hydrophobic anticancer drugs such as paclitaxel (PTX). The purpose of this study was to synthesize novel trans-10, cis-12 conjugated linoleic acid (CLA)-coated SPIONs loaded with PTX to enhance the anti-proliferative activity of PTX. CLA-coated PTX-SPIONs with a particle size and zeta potential of 96.5 ± 0.6 nm and −27.3 ± 1.9 mV, respectively, were synthesized. The superparamagnetism of the CLA-coated PTX-SPIONs was confirmed, with saturation magnetization of 60 emu/g and 29 Oe coercivity. CLA-coated PTX-SPIONs had a drug loading efficiency of 98.5% and demonstrated sustained site-specific in vitro release of PTX over 24 h (i.e., 94% at pH 6.8 mimicking the tumor microenvironment). Enhanced anti-proliferative activity was also observed with the CLA-coated PTX-SPIONs against a lung adenocarcinoma (A549) cell line after 72 h, with a recorded cell viability of 17.1%. The CLA-coated PTX-SPIONs demonstrated enhanced suppression of A549 cell proliferation compared to pristine PTX, thus suggesting potential application of the nanomedicine as an effective site-specific delivery system for enhanced therapeutic activity in NSCLC therapy.

Optimized copolymeric microstructured platforms for smart controlled delivery of an anticoagulant drug: Preparation, in vitro assessment and crossover study in healthy adult human volunteers

In the present study, novel micro-structured copolymeric carriers were developed based on the grafting technology where acrylamide was chemically crosslinked with different types of Eudragits® (NE30D, L100, RL30D, or RS30D) based on a 41*21 factorial design. The designed systems efficiently engulfed the anticoagulant drug dipyridamole (DIP), within their formed entangled mesh of crosslinked polymeric network. An optimized formulation, ECOP4 with a desirability-value of 0.706, (in which DIP is engulfed within a copolymeric network of acrylamide and Eudragit® RS30D) showed high engulfment capacity (97.13 ± 1.34%) and controlled DIP release over 8 h. FTIR studies revealed absence of interactions between DIP and the formed copolymer. ECOP4 was further inserted within an easily-administered safe raft forming system composed of a mixture of LM-pectin and gellan gum. A pharmacokinetic study was performed using human volunteers to determine DIP concentration in their plasma after administering the designed formulation using the high-performance liquid chromatography (HPLC) method. A crossover design was adopted comparing the designed formulation with Persantin® 25 mg tablets as a reference standard. Superior results were obtained for the optimized formulation regarding the measured pharmacokinetic parameters (AUC0-24h, Cmax, and Tmax) with a 2.31 fold increase in relative bioavailability, which reveals the usefulness of the designed grafted dipyridamole formulation in site-specific delivery system.

Study on swelling and drug releasing behaviors of ibuprofen-loaded bimetallic alginate aerogel beads with pH-responsive performance

Bimetallic alginate aerogel beads were prepared by ionotropic gelation method with Ca2+-Ba2+ bimetallic solution and ibuprofen was loaded as a model drug. The swelling and drug releasing behaviors of the beads, especially the influence of barium, were investigated in artificial gastric and intestinal fluids. The results showed that these beads presented higher encapsulation efficiency due to the special structure of aerogel, and barium was beneficial for the more stable structure and drug releasing behavior. The lower swelling capacity of bimetallic beads was observed than monometallic beads. A rapid high-level releasing of ibuprofen was achieved in artificial intestinal fluid, which was up to 96.9% within 1 h, while ibuprofen releasing was avoided in artificial gastric fluid effectively. The drug releasing mechanism of these beads was explored in detail. In the bimetallic crosslinking system, Ba2+ presented a special effect on alginate beads with more sensitive pH response performance. Thus, these beads had more widely potential as a site-specific delivery system, especially for intestinal therapy.

Development and validation of a sensitive LC-MS/MS method for pioglitazone: application towards pharmacokinetic and tissue distribution study in rats.

In the present study, a sensitive LC-MS/MS method was developed and validated to measure pioglitazone (PGZ) concentrations in rat plasma and tissues. The chromatographic separation was achieved by using a YMC Pro C18 column (100 mm × 4.6 mm, 3μ) with a mobile phase consisting of formic acid (0.1% v/v) and acetonitrile (5 : 95) at a flow rate of 0.7 mL min−1 and injection volume of 10 μL (IS: rosiglitazone). Mass spectrometric detection was done using triple quadrupole mass spectrometry using the ESI interface operating in a positive ionization mode. The developed method was validated over a linearity range of 1–500 ng mL−1 with detection and a lower quantification limit of 0.5 ng mL−1 and 1 ng mL−1. The method accuracy ranged from 95.89–98.78% (inter-day) & 93.39–97.68% (intra-day) with a precision range of 6.09–8.12% for inter-day & 7.55–9.87% for intra-day, respectively. The PGZ shows the highest Cmax of 495.03 ng mL−1 in plasma and the lowest Cmax, 24.50 ± 2.71 ng mL−1 in bone. The maximum Tmax of 5.00 ± 0.49 h was observed in bone and a minimum of 1.01 ± 0.05 h in plasma. The AUC(0–24 h and 0–∞) values are highest in plasma (1056.58 ± 65.78 & 1069.38 ± 77.50 ng h−1 mL−1) and lowest in brain (166.93 ± 15.70 &167.12 ± 16.77 ng h−1 mL−1), and the T1/2 was highest in plasma (5.62 ± 0.74 h) and lowest in kidney (2.78 ± 0.19). The developed method was successfully used to measure the PGZ pharmacokinetic and tissue distribution. Further, the developed method could be utilized for validating target organ (adipose tissue) specific delivery of PGZ (nano-formulations) in addition to conventional dosage forms.

Anti-tuberculosis site-specific oral delivery system that enhances rifampicin bioavailability in a fixed-dose combination with isoniazid.

The in vivo release segregation of rifampicin (RIF) and isoniazid (INH) has been proposed as a strategy to avoid RIF acid degradation, which is known as one of the main factors for reduced RIF bioavailability and can result in drug-resistant tuberculosis. So far, this strategy has been scarcely explored. The aims of this study were to investigate the stability and bioavailability of RIF after combination of a very fast release matrix of RIF with a sustained delivery system of INH. A series of INH-alginic acid complexes (AA-INH) was obtained and characterized. Independent and sequential release profile of AA-INH at biorrelevant media of pH 1.20 and 6.80 was explored. In addition, AA-INH was combined with a RIF-carboxymethylcellulose very fast release complex (CMC-RIF) obtained previously and subjected to acid dissolution assays to evaluate RIF acid stability and determine RIF and INH dissolution efficiencies. Finally, a pharmacokinetic study in dogs was carried out. The AA-INH was easily obtained in solid-state. Their characterization revealed its ionic nature, with a loading capacity of around 30%. The dissolution efficiencies (15min) confirmed release segregation in acid media with 7.8 and 65.6% for AA-INH and CMC-RIF, respectively. INH release rate from the AA-INH system was slow in acid media and increased in simulated intestinal media. The complete release of INH was achieved after 2h in simulated intestinal media in the sequential release experiments. The acid degradation of RIF was significantly reduced (36.7%) when both systems were combined and oral administration to dogs revealed a 42% increase in RIF bioavailability. In conclusion, CMC-RIF and AA-INH may be useful for the formulation of a site-specific solid dosage form to overcome some of the main obstacles in tuberculosis treatment. Graphical abstract.

Dexamethasone-Loaded Chitosan Beads Coated with a pH-Dependent Interpolymer Complex for Colon-Specific Drug Delivery

Chitosan (CS) microparticles loaded with dexamethasone were prepared by spray drying, followed by coating with a pH-dependent interpolymer complex based on poly(acrylic acid)/poly(vinyl pyrrolidone) using an water-in-oil emulsion technique. The aim of this research was to evaluate the influence of PAA/PVP coating on the release of dexamethasone from loaded chitosan microparticles, in simulated gastric fluid (SGF, pH=1.2) and simulated intestinal fluid (SIF, pH=6.8). The release of dexamethasone from uncoated loaded CS microparticles was similar in both fluids, and almost complete release of the drug was achieved in 5 hours. In the coated loaded CS microparticles, the release of dexamethasone in SGF was reduced considerably, very close to zero, due to the interpolymer complex formation at low pH, demonstrating that this system applied as pH-dependent coating has a potential as a site-specific delivery system.

Regulation of decellularized tissue remodeling via scaffold-mediated lentiviral delivery in anatomically-shaped osteochondral constructs

Cartilage-derived matrix (CDM) has emerged as a promising scaffold material for tissue engineering of cartilage and bone due to its native chondroinductive capacity and its ability to support endochondral ossification. Because it consists of native tissue, CDM can undergo cellular remodeling, which can promote integration with host tissue and enables it to be degraded and replaced by neotissue over time. However, enzymatic degradation of decellularized tissues can occur unpredictably and may not allow sufficient time for mechanically competent tissue to form, especially in the harsh inflammatory environment of a diseased joint. The goal of the current study was to engineer cartilage and bone constructs with the ability to inhibit aberrant inflammatory processes caused by the cytokine interleukin-1 (IL-1), through scaffold-mediated delivery of lentiviral particles containing a doxycycline-inducible IL-1 receptor antagonist (IL-1Ra) transgene on anatomically-shaped CDM constructs. Additionally, scaffold-mediated lentiviral gene delivery was used to facilitate spatial organization of simultaneous chondrogenic and osteogenic differentiation via site-specific transduction of a single mesenchymal stem cell (MSC) population to overexpress either chondrogenic, transforming growth factor-beta 3 (TGF-β3), or osteogenic, bone morphogenetic protein-2 (BMP-2), transgenes. Controlled induction of IL-1Ra expression protected CDM hemispheres from inflammation-mediated degradation, and supported robust bone and cartilage tissue formation even in the presence of IL-1. In the absence of inflammatory stimuli, controlled cellular remodeling was exploited as a mechanism for fusing concentric CDM hemispheres overexpressing BMP-2 and TGF-β3 into a single bi-layered osteochondral construct. Our findings demonstrate that site-specific delivery of inducible and tunable transgenes confers spatial and temporal control over both CDM scaffold remodeling and neotissue composition. Furthermore, these constructs provide a microphysiological in vitro joint organoid model with site-specific, tunable, and inducible protein delivery systems for examining the spatiotemporal response to pro-anabolic and/or inflammatory signaling across the osteochondral interface.

Evaluation of Ciprofloxacin Floating-Bioadhesive Tablet Formulated with Okra Gum as Multifunctional Polymer

Floating drug delivery systems and bioadhesive drug delivery systems are gastroretentive systems for increasing gastric residence time to obtain improved drug bioavailability. This study was to evaluate the floating and bioadhesive characteristics of Ciprofloxacin tablets formulated with Abelmoschus esculentus gum (okra gum).Okra gum was extracted and granules were prepared using the extracted Okra gum as well as sodium alginate and HPMC at concentrations of 2.5, 5 and 10 % w/w. Ciprofloxacin floating bioadhesive (CFB) tablets were evaluated for hardness, friability, in vitro buoyancy test, ex vivo bioadhesion test and drug release profiles. The floating lag time (FLT) and total floating time (TFT) for CFB tablets formulated with 10% w/w okra gum were 5.7 minutes and 8 hours respectively while the bioadhesive force was 1.324 N. Formulations of ciprofloxacin tablets containing admixtures of okra gum and sodium alginate or HPMC resulted in significant decrease (p < 0.05) in the floating lag times (≤ 3.1 minutes) and significant increase (p < 0.05) in total floating times (> 12 h). The bioadhesive force for CFB tablets containing admixtures of okra gum and sodium alginate or HPMC gave higher values in the range of 1.766 – 2.207 N. The in vitro release profiles for CFB tablets formulated with okra gum alone did not show sustained release below 10 % w/w. Batches FB10 and FB11 containing admixtures showed sustained release with maximum release of 86% at maximum time of 9 h. The dissolution profiles of tablets from batches F10 and F11 compared favourably with the profile for the commercial brand of floating ciprofloxacin tablet, MF. From the study Okra gum has shown to possess good floating and bioadhesive properties and may be utilized in the formulation gastro-retentive dosage form of ciprofloxacin which can possibly be harnessed as a targeted site-specific delivery system in the eradication of Helicobacter pylori in gastric ulcer disease as well as in the treatment of Salmonella typhi induced enteric fever.

Erratum to: Mitochondria-targeting self-assembled nanoparticles derived from triphenylphosphonium-conjugated cyanostilbene enable site-specific imaging and anticancer drug delivery

Subcellular organelle-specific nanoparticles for simultaneous tumor targeting, imaging, and drug delivery are of enormous interest in cancer therapy. Herein, we report a selective mitochondria-targeting probe 1, which was synthesized by incorporating a triphenyl phosphine with a cyanostilbene and a long alkyl chain moiety. Probe 1 was found to display fluorescence via aggregation-induced emission (AIE). The low molecular-weight cyanostilbene-based probe 1, with and without an anticancer drug, formed a narrow homogeneous nanorod with ca. 110 nm of length or nanoparticles with ca. 20 nm diameter in aqueous media. The self-assembled cyanostilbene nanoparticles (N1) selectively accumulated in the mitochondria of cancer cells and emitted fluorescence. N1 was also able to deliver an anticancer drug, doxorubicin (DOX), to the mitochondria with high efficiency. More importantly, N1 exhibited highly selective cytotoxicity for cancer cells over normal cells. The great potential applications of this self-assembled nanoparticle to biological systems result from its ability to aggregate in the mitochondria. This aggregation led to a significant increase in the generation of intracellular reactive oxygen species and to a decrease in the mitochondrial membrane potential in cancer cells. Furthermore, tumor tissue uptake experiments in mice proposed that the self-assembled N1 had the ability to internalize and deliver the anticancer drug into tumor tissues effectively. Moreover, both N1 and N1-encapsulated doxorubicin (N1-DOX) effectively suppressed tumor growth in a xenograft model in vivo. Taken together, our findings indicate that applications of N1 as a mitochondrial targeting probe, drug delivery platform, and chemotherapeutic agent provide a unique strategy for potential image-guided therapy as well as a site-specific delivery system to cancer cells.

Colon cancer targeting using conjugates biomaterial 5-flurouracil.

There has been several research works on the development of an oral delivery system to deliver cytotoxic and chemo preventive agents directly at the targeted site of action with reduced unwanted side effects. The efficacy of the site-specific delivery system of a drug to colon has been proven to increase the drugs concentration at the target site, and thus requires a reduced dose of the drug with minimized side effects. This review includes discussion of the delivery systems of 5-FU using biodegradable materials and some significant outcomes in the pre-clinical development of 5-fluorouracil carriers for the colon cancer.

Synthesis, characterization and in vitro application of pH/temperature sensitive superabsorbent hydrogel of phosphated co-polymer of methacrylic acid and methyl methacrylate ester

This study presents an efficient functionalization method of methacrylic polymers such as Eudragit L100. The incorporation of phosphate groups results in pH/temperature-sensitive superabsorbent hydrogels. They are characterized spectroscopically by 1H-, 13 C- 31P-NMR and FT-IR. Thermal analyses, powder X-ray diffractometry and scanning electron microscopy are also carried out. The swelling experiments of the hydrogels take place in phosphate buffer of different pH values at various temperatures and it is found that the hydrogels follow second order kinetics. The swelling percents are in the range of 5200 and 2160 % at 37 °C and pH 7.2, and up to 7130 % at 55 °C and pH 8.0. The matrices of the hydrogels show bimodal curves on the dissolution study which correlate the drug release with the swelling results. The release of the drug achieves values from 12 to 24 times slower than those obtained with Eudragit L100. The synthesized hydrogels respond to changes in pH and temperature and show a collapsing to swelling phase behavior not reported before. These properties make them useful to be studied as potential in site-specific delivery systems.

Development of engineered nanocarrier for controlled delivery of a protease inhibitor

Background: AIDS is a chronic, progressive syndrome, characterized by intense viral replication and profound immunosuppression, resulting in the development of life threatening opportunistic infections. HIV infection leads to deterioration of immune functions. The objective of the present study was to develop, optimize and characterize engineered nanocarriers for controlled delivery of a protease inhibitor. Lopinavir was the drug of choice as it is an effective antiretroviral drug having specific and prominent anti-HIV action. In the present study, it is envisaged to develop and characterize a controlled delivery system wherein the drug lopinavir (LPV) will be entrapped in engineered nanocarrier. Engineered nanocarriers targeted towards the prespecified target tissues by coupling with mannose delivers the drug in a controlled manner to the site of action. Thus it results in increased bioavailability and avoids the adverse effects associated with the drug. Overall the approach leads to a safe, economical and effective Anti-HIV formulation. Methods & Materials: The uncoupled Solid Lipid Nanoparticles (SLN) were prepared by Solvent diffusion method and then coupled with mannose. Characterization studies were done by Scanning & Transmission Electron Microscopy (SEM & TEM). X-ray diffraction (XRD) and Differential scanning calorimetry (DSC) studies were performed along with the in-vitro studies followed by in-vivo studies on albino rats. Results: In-vitro & in-vivo studies results shows Mannose coated SLNs (MSLN) deliver their contents to macrophage rich organs and tissues, which are the reservoir of HIV. Low elimination and better distribution profile can be achieved by MSLNs. The dose of the antiviral agent can be reduced due to the site-specific delivery from this carrier.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Conclusion: Conclusively, ligand-mediated bio-disposition and cellular interaction of MSLNs, especially at the target sites, would be a focal paradigm for upcoming research in the field of anti-HIV drug delivery. MSLNs have paved the way for the bio-stable, site-specific and ligand-mediated delivery systems with desired therapeutics.

Mesoporous Silica-Based Supports for the Controlled and Targeted Release of Bioactive Molecules in the Gastrointestinal Tract.

Mesoporous silica particles (MSPs) have attracted increasing interest as supports in the design of controlled delivery materials. Besides their excellent properties as loading supports (that is, large surface area and pore volume), the modification of their external surface with molecular/supramolecular ensembles allows the design of gated MSPs. Delivery systems based on gated MSPs show "zero delivery" until an adequate stimulus is present and triggers gate opening and the cargo is released. Encapsulation of bioactive molecules in gated MSPs may improve biological stability, facilitate component handling, mask unpleasant sensorial properties, and modulate the bioaccessibility of target molecules along the gastrointestinal tract. These properties make gated MSPs excellent candidates for encapsulating bioactive molecules and their subsequent utilization in the formulation of functional foods. This text highlights the most significant endogenous triggering stimuli that might be applied to design these site-specific delivery systems, as well as the strategies to develop them. Given the novelty of using MSPs in the food sector, the benefits and current potential limitations of employing MSPs in human food have been identified and discussed.