Potential Drug Delivery System Research Articles

Lomustine’s nanoemulsion as nose-to-brain drug delivery system for CNS tumor treatment

Nose-to-brain delivery allows the direct targeting of drug molecules bypassing the Blood Brain Barrier and systemic effect. Nanoemulsion is one of the novel strategies to deliver drug in this route due to its simplicity in manufacturing, long-term stability, and strong solubilization property for drug. The anticancer drug lomustine had poor oral bioavailability in addition to its serious side effect, therefore, developing more effective drug delivery with direct targeting towards the brain through intra-nasal administration applying nanoemulsion technology is a promising alternative. The work involved lomustine solubility screening in oils, surfactants and cosurfactants as well as emulsifier ratio (Smix) nanoemulsion area was identified using pseudo-ternary phase diagrams. Eighteen nanoemulsion formulas were produced for optimization, then characterized for droplet size, polydispersity index, zeta potential, entrapment efficiency, conductivity, transmittance, dilution, visual transparency, physical stability and in vitro release. The optimum NE formula showed droplet size, zeta potential, polydispersity index, entrapment efficiency, %transmittance, conductivity of 31.31 nm, −30.65 mV, 0.159, 98.12%, 99.08%, and 951 us/cm, respectively. The best formula released 100% lomustine within 15 min which is a promising potential drug delivery system that may deliver the drug quickly and directly to the brain as a safe and effective alternative to oral delivery.

Design of Extended Bisphosphonate-Based Coordination Polymers as Bone-Targeted Drug Delivery Systems for Breast Cancer-Induced Osteolytic Metastasis and Other Bone Therapies.

The coordination between benzene 1,4-bis(bisphosphonic acid) (BBPA), the bisphosphonate (BP) analogue of benzene 1,4-dicarboxylic acid (BDC), and bioactive metals led to the formation of extended bisphosphonate-based coordination polymers (BPCPs). Four distinct crystalline phases were obtained, namely, BBPA-Ca forms I and II, BBPA-Zn, and BBPA-Mg. Among these, BBPA-Ca forms I (7 × 9 Å2) and II (8 × 12 Å2) possess channels large enough to encapsulate 5-fluorouracil (5-FU), a drug prescribed in combination with BPs to treat breast cancer-induced osteolytic metastases (OM). Dissolution curves show a 14% release of BBPA from BBPA-Ca form II in phosphate-buffered saline, while ∼90% was released in fasted-state simulated gastric fluid. These results suggest that this material is relatively stable in neutral environments yet collapses in acidic conditions. Moreover, the phase inversion temperature method decreased the particle size of BBPA-Ca form II, resulting in nano-Ca@BBPA (∼134 d.nm). Binding assays showed a higher affinity of nano-Ca@BBPA (∼97%) to hydroxyapatite than BBPA (∼70%) and significantly higher binding than commercial BPs, zolendronic (3.0×), and risedronic (2.4×) acids after 24 h. Furthermore, both BBPA-Ca form II and nano-Ca@BBPA presented comparable drug loading and release (∼30 wt % 5-FU) relative to BDC-based CCs (UiO-66, MIL-53, and BDC-Zr) where other pharmaceutical compounds (caffeine, ibuprofen, aspirin, and α-cyano-4-hydroxycinnamic acid) have been encapsulated. Cell viability assays established that drug-loaded nano-Ca@BBPA increases the cytotoxicity of a triple-negative human breast cancer cell line (MDA-MB-231) when compared to 5-FU (%RCV = 8 ± 5 vs 75 ± 1% at a 100 μM). At the same concentration, no significant decrease in cell viability was observed for normal human osteoblast-like hFOB 1.19 cells (%RCV = 85 ± 1%). Collectively, these results demonstrate the feasibility of nano-Ca@BBPA as a potential drug delivery system (DDS), with high affinity to bone tissue, to treat bone-related diseases such as OM.

Cyclotide nanotubes as a novel potential Drug-Delivery System: Characterization and biocompatibility

Cyclotides are a class of cyclic peptides that can be self-assembled. This study aimed to discover the properties of cyclotide nanotubes. We performed differential scanning calorimetric (DSC) to characterize their properties. Then, we incorporated the coumarin as a probe and identified the morphology of nanostructures. The stability of cyclotide nanotubes after 3 months of keeping at −20 °C was determined by field emission scanning electron microscopy (FESEM). The cytocompatibility of cyclotide nanotubes was evaluated on peripheral blood mononuclear cells. In vivo, studies were also conducted on female C57BL/6 mice by intraperitoneally administration of nanotubes at 5, 50, and 100 mg/kg doses. Blood sampling was done before and 24 h after nanotube administration and complete blood count tests were conducted. DSC thermogram showed that the cyclotide nanotubes were stable after heating until 200 °C. Fluorescence microscopy images proved that the self-assembled structures of cyclotide can encapsulate the coumarin. FESEM proved that these nanotubes were stable even after 3 months. The results of the cytotoxicity assay and in-vivo study confirmed that these novel prepared nanotubes were biocompatible. These results suggested that the cyclotide nanotubes could be considered as a new carrier in biological fields while they are biocompatible.

Precipitative Coating of Calcium Phosphate on Microporous Silica–Titania Hybrid Particles in Simulated Body Fluid

Titania and silica have been recognized as potential drug delivery system (DDS) carriers. For this application, controllable biocompatibility and the suppression of the initial burst are required, which can be provided by a calcium phosphate (CP) coating. However, it is difficult to control the morphology of a CP coating on the surface of carrier particles owing to the homogeneous nucleation of CP. In this study, we report the development of a CP-coating method that homogeneously corresponds to the shapes of silica–titania (SiTi) porous nanoparticles. We also demonstrate that controlled surface roughness of CP coatings could be achieved in SBF using SiTi nanoparticles with a well-defined spherical shape, a uniform size, and a tunable nanoporous structure. The precipitation of CP was performed on mono-dispersed porous SiTi nanoparticles with different Si/Ti molar ratios and pore sizes. The pore size distribution was found to significantly affect the CP coating in SBF immersion; the surfaces of the nanoparticles with bimodal pore sizes of 0.7 and 1.1–1.2 nm became rough after CP precipitation, while those with a unimodal pore size of 0.7 nm remained smooth, indicating that these two pore sizes serve as different nucleation sites that lead to different surface morphologies.

Preparation and Characterization of 5‐Fluorouracil Loaded Cellulose and Exosome Nanocarriers: Sustained Release Behavior and Cytotoxicity Studies**

AbstractIn recent years, much effort has been devoted to designing nanoparticle drug delivery systems and improving the efficacy of anticancer drugs. This study focused on the preparation of a novel biocompatible nanocarrier based on bacterial cellulose (BC) in the presence of exosome (Exo) for the controlled release of 5‐fluorouracil (5‐FU), known as 5‐FU.Exo@BC. The physicochemical properties of 5‐FU.Exo@BC were thoroughly characterized using field emission scanning electron microscopy (FESEM), differential scanning calorimetry (DSC), Fourier‐transform infrared spectroscopy (FTIR), and X‐ray diffraction (XRD). These results confirmed the successful preparation of 5‐FU.Exo@BC. The release behavior of 5‐FU.Exo@BC compared with 5‐FU and 5‐FU@BC demonstrated a significant sustained release over 162 h. The release mechanism of the above three systems followed Korsmeyer‐Peppas with non‐Fickian diffusion for 5‐FU@BC and 5‐FU.Exo@BC. Furthermore, the viability of HT‐29 cells (human colon cancer cell lines) against BC, 5‐FU@BC and 5‐FU.Exo@BC indicated that 5‐FU has promising efficacy in 5‐FU.Exo@BC system. Subsequently, the prepared bio‐nanocomposite could be suggested as a potential drug delivery system with an effective controlled‐release function.

Synthesis and characterization of quercetin-layer double hydroxide (LDH) nanohybrid and their enhanced antioxidant activity

ABSTRACT. This research included the synthesis of pristine nitrate-type Zn2Al-LDH by means of Co-precipitation, which was then followed by hydrothermal treatment. Ion exchange is used to stabilize the produced pristine LDH nano layer, which is used for the encapsulation of bioactive molecules. Quercetin, which has an antioxidant function, is used. XRD was used to investigate the newly synthesized quercetin-LDH (QC-LDH) compound. Quercetin was discovered to be entirely deprotonated as a result of XRD research, and it was also shown to be stabilized in between LDH lattices as a result of electrostatic contact. On the basis of the diphenyl picrylhydrazyl (DPPH) method, the anti-oxidant property was discussed, and it was discovered that the quercetin that was free from the LDH layer helped as an owing antioxidant to scavenge DPPH radicals in ethanol solvent at concentrations ranging from 80-100%, depending on the concentration level. The powder X-ray diffraction patterns indicate that the incorporation of quercetin into the interlayer led to an expansion of the interlayer arrangement to 0.88 and 1.46 nm, respectively. According to the findings of a variety of characterization techniques, the QC-LDH may be regarded as a good antioxidant material with potential drug delivery system.
 
 KEY WORDS: Layer double hydroxide, Antioxidant activity, Quercetin, Biocompatibility
 
 Bull. Chem. Soc. Ethiop. 2023, 37(4), 917-929.
 DOI: https://dx.doi.org/10.4314/bcse.v37i4.9

Application of Nano Drug Delivery System (NDDS) in Cancer Therapy: A Perspective.

Cancer is the biggest killer that threatens human health. Poor bioavailability and strong drug resistance of cancer drugs are common defects. In recent years, drug delivery therapy based on nanotechnology has become a focused research area, and nano drug delivery system has been widely studied in cancer treatment. Based on the articles and patents published on the application of nano drug delivery systems in cancer treatment in the past five years, this paper summarizes the types of nano drug delivery systems and their advantages and limitations in cancer treatment in order to provide a reference for future anticancer research on nano drug delivery systems. This perspective summarizes the types of nano drug delivery systems and their advantages and limitations in cancer treatment in recent five years, and proposes the development direction of nano drug delivery systems in the future. Based on the review of articles and patents, we found that the nano drug delivery system is mainly divided into encapsulated nano drug delivery system and covalently bound nanoprodrug delivery system. Its advantages in cancer treatment are mainly reflected in enhancing drug stability, improving bioavailability, reducing toxicity and better application in cancer diagnosis. However, nano drug delivery system is a new field of science, some of these drug delivery systems might have high toxicity and low bioavailability; the off-target phenomenon often occurs, and most studies are just focused on the early stage, its mechanism of action, clinical efficacy and patient tolerance, and the toxicity of treatment remains to be further investigated. This perspective systematically summarizes the types of nano drug delivery systems and their advantages and limitations in cancer treatment based on the published articles and patents obtained in the last five years. Future research on nano drug delivery system should consider the potential risks, and stable and efficient nano drug delivery systems should be designed to treat cancer by changing or functionalizing the nanomaterial.

Hyaluronic acid oligosaccharide-modified zeolitic imidazolate framework-8 nanoparticles loaded with oxaliplatin as a targeted drug-delivery system for colorectal cancer therapy.

Aim: Exploring a nanoscale targeted drug-delivery system (DDS) for oxaliplatin (Oxa) to improve its therapeutic effect in colorectal cancer. Materials & methods: Nanoparticles were prepared using zeolitic imidazole framework-8 (ZIF-8) modified by hyaluronic acid oligosaccharide (oHA) as an Oxa carrier (oHA@ZIF-8@Oxa). After multiple characterizations, the therapeutic efficacy of the DDS was evaluated by cytotoxicity testing and a nude mouse tumor transplantation experiment in vivo. Results: The results of characterization showed the DDS was homogeneous in morphology and uniform in dispersion. The drug loading of Oxa was 11.82% and the encapsulation efficiency was 90.8%. The cytotoxicity test and in vivo experiments showed that oHA@ZIF-8@Oxa had a more significant anticolorectal cancer effect than free Oxa. Conclusion: This work offers a promising potential DDS for enhancing the anticolorectal cancer effect of Oxa.

ZIF-8 based microspheres with ordered mesopores and dual responsive surfaces

Zeolite imidazolate framework-8 (ZIF-8) is considered to be a potential drug delivery system for anticancer drugs. In order to address such challenges as its dosage limitation, toxicity, intelligent responsiveness, a ZIF-8 based biocompatible porous material of micron-size (ZIF-8 microphere/DOX@ PCM-PDA composites, ZMDPCs) is designed with ordered topology and dual responsive surfaces. The large specific surface area and hierarchical pores endow ZMDPCs with high loading capacity (1 mg could carry 3.8 mg DOX). The biocompatibility is enhanced by polydopamine (PDA) decoration. Moreover, PDA could be a photothermal converting material to trigger phase transition of PCM (as a thermal response valve) through NIR irradiation. Drug release could be controllable by stimulation of NIR or pH. With such biocompatibility, degradability and responsive surfaces, ZMDPCs show promising potential as a drug delivery vehicle.

Surface engineered mesoporous silica carriers for the controlled delivery of anticancer drug 5-fluorouracil: Computational approach for the drug-carrier interactions using density functional theory.

Introduction: Drug delivery systems are the topmost priority to increase drug safety and efficacy. In this study, hybrid porous silicates SBA-15 and its derivatives SBA@N and SBA@3N were synthesized and loaded with an anticancer drug, 5-fluorouracil. The drug release was studied in a simulated physiological environment. Method: These materials were characterized for their textural and physio-chemical properties by scanning electron microscopy (SEM), nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), small-angle X-ray diffraction (SAX), and nitrogen adsorption/desorption techniques. The surface electrostatics of the materials was measured by zeta potential. Results: The drug loading efficiency of the prepared hybrid materials was about 10%. In vitro drug release profiles were obtained in simulated fluids. Slow drug release kinetics was observed for SBA@3N, which released 7.5% of the entrapped drug in simulated intestinal fluid (SIF, pH 7.2) and 33% in simulated body fluid (SBF, pH 7.2) for 72h. The material SBA@N presented an initial burst release of 13% in simulated intestinal fluid and 32.6% in simulated gastric fluid (SGF, pH 1.2), while about 70% of the drug was released within the next 72h. Density functional theory (DFT) calculations have also supported the slow drug release from the SBA@3N material. The release mechanism of the drug from the prepared carriers was studied by first-order, second-order, Korsmeyer-Peppas, Hixson-Crowell, and Higuchi kinetic models. The drug release from these carriers follows Fickian diffusion and zero-order kinetics in SGF and SBF, whereas first-order, non-Fickian diffusion, and case-II transport were observed in SIF. Discussion: Based on these findings, the proposed synthesized hybrid materials may be suggested as a potential drug delivery system for anti-cancer drugs such as 5-fluorouracil.

Therapeutic potential of oxo-triarylmethyl (oxTAM) as a targeted drug delivery system for nitrosourea and fluorouracil anticancer drugs; A first principles insight

In this study, oxygenated triarylmethyl (oxTAM) is investigated by DFT calculations as a drug carrier framework for Nitrosourea (NU) and Fluorouracil (FU) drugs. Based on the adsorption analysis i.e., energies and distances between interacting atoms, it is found that oxTAM exhibits excellent carrier abilities for the delivery of FU (−1.53 eV & 2.00 Å) and NU (−1.33 eV & 2.12 Å) drugs. NCI and QTAIM results indicate the presence of hydrogen bonding in drug-carrier complexes. The values of dipole moment and global chemical descriptors show the significant reactivity of oxTAM for NU and FU drugs. Based on electronic property analysis, FU@oxTAM has a higher adsorption trend for complexation with oxTAM as compared to NU@oxTAM. Moreover, FU can easily release from the carrier due to the decreasing adsorption stability after protonation under an acidic environment as well as a short recovery time observed for the oxTAM carrier surface. Keeping in view all the above parameters, we inferred that oxTAM can serve as a potential drug delivery system for anticancer drugs including, Nitrosourea and Fluorouracil drugs.

Abstract 829: Evaluation of SK-N-DZ CLENs as a potential drug delivery system for selective targeting of neuroblastoma cells

Abstract Background: Neuroblastoma (NB) is a malignancy of the neuroendocrine system affecting infants. NB is highly resistant to drug therapy, which leads to ineffective treatments and increased refractory. Current treatments have low specificity to targeted NB cells resulting in unwanted side effects. A drug delivery system that can overcome these problems is urgently needed. Incorporating drugs in optimized lipid nanoparticles such as liposomes have proven to be an effective method for drug targeting. To achieve better cellular selectivity, lipid membrane extract (LE) is derived from NB cells using a modified Dyer and Blight lipid extraction procedure. The objective of the study was to determine an optimized cell membrane lipid-extracted nanoliposomes (CLENs) for the NB cell model while considering physicochemical properties (i.e. size and molecular charge) and composition of the preparation. Methods: The neuroblastoma cell line, SK-N-DZ, was used for drug selectivity study. Expanded culture of SK-N-DZ was employed for cellular extraction purposes. The method for lipid membrane extraction was previously reported by Alharbi and Campbell, (AAPS Open 4,5(2018)). SK-N-DZ lipid extract was the main ingredient to prepare SK-N-DZ CLENs. Phase I of the study is to prepare CLENs with various compositions of DOPC, cholesterol, DPPE-PEG5000 and SK-N-DZ lipid extract. DPPE-Rhodamine was used for fluorescence and cellular uptake studies. Phase II of the study evaluated the effect of SK-N-DZ lipid extraction inclusion on drug incorporation, cellular uptake and selectivity, and cytotoxicity. Invitrogen alamarBlue HS in vitro assay was used to determine cell viability for cytotoxicity studies. SK-N-SH (brain tissue), BT-20 (breast tissue) and G401 (kidney tissue) cell lines served as negative controls. Results: The results from the cellular uptake optimization studies revealed that the optimized composition and ratio for SK-N-DZ CLENs was DOPC/Cholesterol/LE/PEG (65/10/20/5). The average particle size and value for zeta potential was 164 nm +/- 1.2 and -7.92 +/- 1.55 mV, respectively. The inclusion of SK-N-DZ lipid membrane extract (2, 10, 20 and 40 mol%) in preparation of CLENs increased cellular uptake by SK-N-DZ cells compared to corresponding control (no LE included). No difference observed in cellular uptake of preparations containing 20 and 40 mol% of LE. The additional inclusion of cholesterol (10, 20, 40 mol%) increased overall cellular uptake of preparations compared to CLENs without the additional cholesterol content. Overall, the inclusion of PEG (5, 10, and 20 mol%) in SK-N-DZ CLENs increased their uptake by the target cell population. Conclusion: In conclusion, the inclusion of SK-N-DZ lipid membrane extract in the nanoliposome preparations increased their overall cellular uptake by SK-N-DZ target cells. Additional cellular selectively and cytotoxicity studies are currently underway. Citation Format: Kevin Bumanglag, Thi Tran, Robert Campbell, Yishan Li. Evaluation of SK-N-DZ CLENs as a potential drug delivery system for selective targeting of neuroblastoma 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 829.

Red blood cell membrane-camouflaged poly(lactic-co-glycolic acid) microparticles as a potential controlled release drug delivery system for local stellate ganglion microinjection.

The stellate ganglion (SG) is a part of the sympathetic nervous system that has important regulatory effects on several human tissues and organs in the upper body. SG block and intervention have been clinically and preclinically implemented to manage chronic pain in the upper extremities, neck, head, and upper chest as well as chronic heart failure. However, there has been very limited effort to develop and investigate polymer-based drug delivery systems for local delivery to the SG. In this study, we fabricated red blood cell (RBC) membrane-camouflaged poly(lactic-co-glycolic acid) (PLGA) (PLGAM) microparticles for use as a potential long-term controlled release system for local drug delivery. The structure, size, and surface zeta potential results indicated that the spherical PLGAM microparticles were successfully fabricated. Both PLGA and PLGAM microparticles exhibited biocompatibility with human adipose mesenchymal stem cells (ADMSC) and satellite glial cells and showed hemocompatibility. In addition, both PLGA and PLGAM displayed no significant effects on the secretion of proinflammatory cytokines by human monocyte derived macrophages in vitro. We microinjected microparticles into rat SGs and evaluated the retention time of microparticles and the effects of the microparticles on inflammation in vivo over 21 days. Subsequently, we fabricated drug-loaded PLGAM microparticles by using GW2580, a colony stimulating factor-1 receptor inhibitor, as a model drug and assessed its encapsulation efficiency, drug release profiles, biocompatibility, and anti-inflammatory effects in vitro. Our results demonstrated the potential of PLGAM microparticles for long-term controlled local drug release in the SG. STATEMENT OF SIGNIFICANCE: SG block by locally injecting therapeutics to inhibit the activity of the sympathetic nerves provides a valuable benefit to manage chronic pain and chronic heart failure. We describe the fabrication of RBC membrane-camouflaged PLGA microparticles with cytocompatibility, hemocompatibility, and low immunogenicity, and demonstrate that they can be successfully and safely microinjected into rat SGs. The microparticle retention time within SG is over 21 days without eliciting detectable inflammation. Furthermore, we incorporate a CSF-1R inhibitor as a model drug and demonstrate the capacities of long-term drug release and regulation of macrophage functions. The strategies demonstrate the feasibility to locally microinject therapeutics loaded microparticles into SGs and pave the way for further efficacy and disease treatment evaluation.

RSPO3 Furin domain-conjugated liposomes for selective drug delivery to LGR5-high cells.

The transmembrane receptor LGR5 potentiates Wnt/β-catenin signaling by binding both secreted R-spondin (RSPOs) and the Wnt tumor suppressors RNF43/ZNRF3, directing clearance of RNF43/ZNRF3 from the cell surface. Besides being widely used as a stem cell marker in various tissues, LGR5 is overexpressed in many types of malignancies, including colorectal cancer. Its expression characterizes a subpopulation of cancer cells that play a crucial role in tumor initiation, progression and cancer relapse, known as cancer stem cells (CSCs). For this reason, ongoing efforts are aimed at eradicating LGR5-positive CSCs. Here, we engineered liposomes decorated with different RSPO proteins to specifically detect and target LGR5-positive cells. Using fluorescence-loaded liposomes, we show that conjugation of full-length RSPO1 to the liposomal surface mediates aspecific, LGR5-independent cellular uptake, largely mediated by heparan sulfate proteoglycan binding. By contrast, liposomes decorated only with the Furin (FuFu) domains of RSPO3 are taken up by cells in a highly specific, LGR5-dependent manner. Moreover, encapsulating doxorubicin in FuFuRSPO3 liposomes allowed us to selectively inhibit the growth of LGR5-high cells. Thus, FuFuRSPO3-coated liposomes allow for the selective detection and ablation of LGR5-high cells, providing a potential drug delivery system for LGR5-targeted anti-cancer strategies.

Formulation, Characterization and In-vitro Evaluation of Prolonged Local Drug Delivery of Antimicrobial on Bone Tissue Formation

The present study aim to prepare and characterize prolonged local drug delivery of antimicrobial on bones tissue formation and its In-vitro evaluation. The results of drug released pattern were analysed after coating. In formulation (F1), the drug release was steep till 73%, where coating showed no such retardation effect. After 73% of drug release, F1 showed prolonged release of drug even after coating with 1% and 2% Chitosan, F2 and F3 showed prolonged better effect with 1% as compared to 2% Chitosan coating. In formulations containing one part of bioglass (F4 and F6) Showed prolonged release by 2% coating followed by 1% Chitosan coating. F5 was the exception where coating favoured dissolution. F8 and F9 showed prolonged release of drug by 1% than 2% Chitosan. In-case of In-vitro study, concentration was maintained above MIC i,e above 0.032 except in 816 hours where the drug concentration was observed below MIC (Fig No-14). F4C was found to be the best i,e 0.880 (Table No-06) for prolonged drug release over 6 weeks. FTIR study confirmed that characteristic peaks showed by Moxifloxicin (Fig No-3 & Table No-5) were 719cm-1, 1045cm-1, 1702cm-1 and 3327cm-1 which were also shown by developed formulations (725cm-1, 1051cm-1, 1703cm-1 and 3543cm-1). For In-vitro bioactivity, SEM were also performed after 24hrs (Fig No-15) and 48hrs (Fig No-16), the intensity of the HAP in 48hrs was more as compared to 24rs which confirmed that formulation is able to induced new bone cell after implantation. This result indicates that these newly prepared formulations could be a potential drug delivery system in osteomylietis condition (induces new bone cell) and can be helpful for the scientists for the particular field of study in near future.

Synthesis, characterization, and in vitro anti-tumor activity studies of the hyaluronic acid-mangiferin-methotrexate nanodrug targeted delivery system

In this study, to increase the accumulation of MTX in the tumor site and reduce the toxicity to normal tissues by MA, a novel nano-drug delivery system comprised of hyaluronic acid (HA)-mangiferin (MA)-methotrexate (MTX) (HA-MA-MTX) was developed by a self-assembly strategy. The advantage of the nano-drug delivery system is that MTX can be used as a tumor-targeting ligand of the folate receptor (FA), HA can be used as another tumor-targeting ligand of the CD44 receptor, and MA serves as an anti-inflammatory agent. 1HNMR and FT-IR results confirmed that HA, MA, and MTX were well coupled together by the ester bond. DLS and AFM images revealed that the size of HA-MA-MTX nanoparticles was about ~138 nm. In vitro cell experiments proved that HA-MA-MTX nanoparticles have a positive effect on inhibiting K7 cancer cells while having relatively lower toxicity to normal MC3T3-E1 cells than MTX does. All these results indicated that the prepared HA-MA-MTX nanoparticles can be selectively ingested by K7 tumor cells through FA and CD44 receptor-mediated endocytosis, thus inhibiting the growth of tumor tissues and reducing the nonspecific uptake toxicity caused by chemotherapy. Therefore, these self-assembled HA-MA-MTX NPs could be a potential anti-tumor drug delivery system.

Fabrication of Transdermal Gel Embedded with Solid Lipid Nanoparticles of Indomethacin

Rheumatoid/osteoarthritis is one of the most common causes for lacking behind in the health sector. Medication in the form of tablets are already available in the market but has disadvantages. When these medicines are taken orally it cause heartburn and discomfort. The introduction of transdermal drug delivery is expected to solve this problem of side eff ects associated with oral delivery of drug. In the present study, indomethacin was loaded in solid lipid nanoparticles (SLN) which are then embedded in Carbopol gel for transdermal application. The solvent evaporation ultrasonication method was used for making SLNs. The formulation was evaluated for various parameters such as ; particle size and zeta potential of SLN using zetasizer as an instrument and gel formulations were evaluated for pH, spreading coeffi cient, viscosity, visual appearance and clarity. Gel-embedded SLN formulation was found to be a potential transdermal drug delivery system for NSAIDs like indomethacin to treat ailments like rheumatoid arthritis or osteoarthritis.

Calcium Phosphate Silicate Microspheres with Soybean Lecithin as a Sustained-Release Bone Morphogenetic Protein-Delivery System for Bone Tissue Regeneration.

Bone morphogenetic protein (BMP) is a growth factor that effectively promotes osteogenesis. Microsphere-based drug-delivery systems can facilitate an increase in the local concentration of BMP, thus promoting bone formation. In this study, calcium phosphate silicate (CPS) microspheres were used as drug-loading systems for BMP. Three groups─CPS, CPS + BMP, and CPS + BMP + soy lecithin (SL)─were set up, where SL was used to prolong the osteogenic effect of the microsphere system. Bone marrow mesenchymal stem cells and femoral defects in rats were used to compare the osteogenic ability of the three groups. The results indicated that CPS microspheres were good carriers of BMP, facilitating a smoother release into the cells and tissues. SL loading improved the loading rate of BMP, which promoted the osteogenic effect of the microspheres with BMP. We propose CPS microspheres as potential drug-delivery systems that can be effectively used in the treatment of bone defects.

Controlled release of a non-steroidal anti-inflammatory drug from a photocurable polymeric calcium phosphate cement

In this research, a photocurable composite based on tetracalcuim phosphate ceramic and, hydroxyethyl methacrylate-modified poly(acrylic-maleic acid) was developed and studied as a potential drug delivery system for bone defects. Different concentrations (5, 10 and 20 wt. %) of a non-steroidal anti-inflammatory drug, Indomethacin, were loaded on to the composite and its release behavior was investigated in phosphate buffered solution during 504 h. The obtained release data were fitted by both power law (Peppas) and Weibull equations. The composites were also characterized after different soaking periods using X-ray diffractometry (XRD), scanning electron microscopy (SEM) and Fourier transforming infrared spectroscopy. The results of XRD and SEM analyses revealed the formation of nanosized needle/flake-like apatite crystals on the composites surfaces; however, better apatite formation was observed for the composites loaded with higher amounts of Indomethacin. The morphological observations and quantitative estimations revealed that the loaded composites were gradually degraded in the phosphate-buffered saline. Moreover, a controlled release of Indomethacin was found from the composites in which a higher drug concentration led to a more drug level as well as sustained release profile. In drug release modeling, better regression coefficient was obtained from the Weibull equation, compared to the power law, meaning that the Weibull equation suggests a better description of the indomethacin release from the composites during the whole period of the test. In conclusion, the photocurable composite with apatite formation ability can be successfully used for the controlled release of indomethacin as an anti-inflammatory drug in bone defects.

Potential of Lipid-Based Nanocarriers against Two Major Barriers to Drug Delivery-Skin and Blood-Brain Barrier.

Over the past few years, pharmaceutical and biomedical areas have made the most astounding accomplishments in the field of medicine, diagnostics and drug delivery. Nanotechnology-based tools have played a major role in this. The implementation of this multifaceted nanotechnology concept encourages the advancement of innovative strategies and materials for improving patient compliance. The plausible usage of nanotechnology in drug delivery prompts an extension of lipid-based nanocarriers with a special reference to barriers such as the skin and blood-brain barrier (BBB) that have been discussed in the given manuscript. The limited permeability of these two intriguing biological barriers restricts the penetration of active moieties through the skin and brain, resulting in futile outcomes in several related ailments. Lipid-based nanocarriers provide a possible solution to this problem by facilitating the penetration of drugs across these obstacles, which leads to improvements in their effectiveness. A special emphasis in this review is placed on the composition, mechanism of penetration and recent applications of these carriers. It also includes recent research and the latest findings in the form of patents and clinical trials in this field. The presented data demonstrate the capability of these carriers as potential drug delivery systems across the skin (referred to as topical, dermal and transdermal delivery) as well as to the brain, which can be exploited further for the development of safe and efficacious products.