Vehicles For Controlled Release Research Articles

Stabilization of Picea abies Spruce Bark Extracts within Ice-Templated Porous Dextran Hydrogels

Porous hydrogels have brought more advantages than conventional hydrogels when used as chromatographic materials, controlled release vehicles for drugs and proteins, matrices for immobilization or separation of molecules and cells, or as scaffolds in tissue engineering. Polysaccharide-based porous hydrogels, in particular, can address challenges related to bioavailability, solubility, stability, and targeted delivery of natural antioxidant compounds. Their porous structure enables the facile encapsulation and controlled release of these compounds, enhancing their therapeutic effectiveness. In this context, in the present study, the cryogelation technique has been adopted to prepare novel dextran (Dx)-based porous hydrogels embedding polyphenol-rich natural extract from Picea abies spruce bark (SBE). The entrapment of the SBE within the Dx network was proved by FTIR, SEM, and energy-dispersive X-ray spectroscopy (EDX). SEM analysis showed that entrapment of SBE resulted in denser cryogels with smaller and more uniform pores. Swelling kinetics confirmed that higher concentrations of Dx, EGDGE, and SBE reduced water uptake. The release studies demonstrated the effective stabilization of SBE in the Dx-based cryogels, with minimal release irrespective of the approach selected for SBE incorporation, i.e., during synthesis (~3–4%) or post-synthesis (~15–16%). In addition, the encapsulation of SBE within the Dx network endowed the hydrogels with remarkable antioxidant and antimicrobial properties. These porous biomaterials could have broad applications in areas such as biomedical engineering, food preservation, and environmental protection, where stability, efficacy, and safety are paramount.

Synthesis and in vitro study of biodegradable and thermoresponsive polymer based on polysuccinimide for drug delivery

Hydrogels, defined as polymer networks with a high water content and insoluble in water, have emerged as pivotal materials in biomedical research due to their resemblance to the natural extracellular matrix. The aim of this study is to develop an injectable, thermoresponsive, and biodegradable hydrogel. The hydrogel (PSI-t) was derived from poly (aspartic acid) (PSI) by grafting hydrophobic dodecylamine (DA) and hydrophilic ethanolamine (EA) groups onto its backbone. PSI-t was found to exhibit a unique sol state at room temperature, which facilitates facile injection, and undergoes rapid gelation at physiological temperatures, highlighting its potential as an injectable thermosensitive hydrogel for targeted drug delivery. In vitro tests confirmed the biocompatibility of the thermosensitive hydrogel, and sustained drug release studies using the model drug, acetaminophen (AP), underscored the efficacy of the hydrogel as a controlled release vehicle. Furthermore, the hydrogel was found to be easily eliminated through bio-hydrolysis, thus enabling prolonged drug effects while mitigating any potential toxicity. These findings suggest that PSI-t is a promising candidate for an innovative and injectable drug delivery system in biomedical applications.

Montmorillonite-Sodium Alginate Oral Colon-Targeting Microcapsule Design for WGX-50 Encapsulation and Controlled Release in Gastro-Intestinal Tract.

The montmorillonite-sodium alginate (MMT-SA) colon-targeting microcapsules have been designed as a WGX-50 encapsulation and controlled release vehicle used in oral administration. The MMT-SA microcapsule was formed from a cross-linking reaction, and the stable micropore in the microcapsule changed with a different MMT-SA mixed mass ratio. The MMT-SA microcapsule has a reinforced micropore structure and an enhanced swell-dissolution in SIF and SCF with alkaline environment, which is attributed to the incorporated MMT. The MMT-SA microcapsule exhibited a high WGX-50 encapsulation rate up to 98.81 ± 0.31% and an obvious WGX-50 controlled release in the simulated digestive fluid in vitro. The WGX-50 loaded with MMT-SA microcapsule showed a weak minimizing drug loss in SGF (Simulated Gastric Fluid) with an acidic environment, while it showed a strong maximizing drug release in SIF (Simulated Intestinal Fluid) and SCF (Simulated Colonic Fluid) with an alkaline environment. These features make the MMT-SA microcapsule a nominated vehicle for colon disease treatment used in oral administration.

Temperature-responsive PCL-PLLA nanofibrous tissue engineering scaffolds with memorized porous microstructure recovery.

Biomaterial scaffolds in tissue engineering facilitate tissue regeneration and integration with the host. Poor healing outcomes arise from lack of cell and tissue infiltration, and ill-fitting interfaces between matrices or grafts, resulting in fibrous tissue formation, inflammation, and resorption. Existing tissue engineering scaffolds struggle to recover from deformation to fit irregularly shaped defects encountered in clinical settings without compromising their mechanical properties and favorable internal architecture. This study introduces a synthetic biomaterial scaffold composed of high molecular weight poly (L-lactic acid) (PLLA) and an interpenetrating network of poly (ε-caprolactone) (PCL), in a composition aiming to address the need for conformal fitting synthetic matrices which retain and recover their advantageous morphologies. The scaffold, known as thermosensitive memorized microstructure (TS-MMS), forms nanofibrous materials with memorized microstructures capable of recovery after deformation, including macropores and nanofibers. TS-MMS nanofibers, with 50-500 nm diameters, are formed via thermally induced phase separation (TIPS) of PLLA after in situ polymerization of PCL-diacrylate. A critical partial-melting temperature of TS-MMS at 52°C enables bulk deformation above this temperature, while retaining the nanofibrous and macroporous structures upon cooling to 37°C. Incorporation of drug-loaded poly (lactide-co-glycolide) (PLGA) nanoparticles directly into TS-MMS nanofibers during fabrication allows sustained release of a model drug for up to 40 days. Subcutaneous implantation in vivo using LysM-Cre;td-Tomato; Col1eGFP mice demonstrates successful cellularization and integration of deformed/recovered TS-MMS materials, surpassing the limitations of deformed PLLA scaffolds, to facilitate cell and vasculature infiltration requisite for successful bone regeneration. Additionally we demonstrated a method for embedding controlled release vehicles directly into the scaffold nanofibers; controlled release of simvastatin enhances vascularization and tissue maturation. TS-MMS scaffolds offer promising improvements in clinical handling and performance compared to existing biomaterial scaffolds.

Study of Gelatin-grafted-2-Acrylamido-2-methylpropane sulfonic acid hydrogels as a controlled release vehicle for amorphous solid dispersion of Tripterygium Wilfordii bioactive constituents

The development of controlled-release preparations for herbal medicines remains challenging due to their complex compositions and distinct physicochemical properties. Tripterygium Wilfordii (TWHF) is a traditional Chinese medicine used to treat inflammatory diseases like rheumatoid arthritis, neurodegenerative and autoimmune diseases. The main active ingredients include diterpenes, triterpenes and alkaloids. These agents have poor pharmacokinetic and physicochemical characteristics, making it difficult to achieve therapeutic benefits. In the present study, a solid dispersion of TWHF (TWHF-SD) was prepared and loaded into Gelatin-grafted-2-Acrylamido-2-methylpropane sulfonic acid hydrogels (Gelatin-g-AMPS) for controlled drug release. A total of 48 compounds were identified in TWHF-SD using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) analysis. The hydrogel's structure and physicochemical properties were confirmed by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Thermogravimetric analysis(TGA), and Differential Scanning Calorimetry (DSC). Studies regarding hydrogel structure–function relationships were conducted, such as average weight between two or mor crosslinks (Mc), polymer volume fraction (V2,s), and diffusion coefficient (D). Hydrogel swelling and drug release from loaded hydrogels were slightly higher at pH 1.2 (swelling ratio of 60.84%, drug release of 85.08) than at pH 7.4 (swelling ratio of 46.46%, drug release of 75.03%) after 48 h. The gel fraction of hydrogel increased with increasing polymer/crosslinker ratios. Additionally, in vitro studies confirmed that the developed hydrogels were effective against bacterial growth and had good antioxidant properties.

New Methacrylated Biopolymer-Based Hydrogels as Localized Drug Delivery Systems in Skin Cancer Therapy.

The aim of the present work was to obtain drug-loaded hydrogels based on combinations of dextran, chitosan/gelatin/xanthan, and poly (acrylamide) as a sustained and controlled release vehicle of Doxorubicin, a drug used in skin cancer therapy that is associated with severe side effects. Hydrogels for use as 3D hydrophilic networks with good manipulation characteristics were produced using methacrylated biopolymer derivatives and the methacrylate group's polymerization with synthetic monomers in the presence of a photo-initiator, under UV light stimulation (365 nm). Transformed infrared spectroscopy analysis (FT-IR) confirmed the hydrogels' network structure (natural-synthetic composition and photocrosslinking), while scanning electron microscopy (SEM) analysis confirmed the microporous morphology. The hydrogels are swellable in simulated biological fluids and the material's morphology regulates the swelling properties: the maximum swelling degree was obtained for dextran-chitosan-based hydrogels because of their higher porosity and pore distribution. The hydrogels are bioadhesive on a biological simulating membrane, and values for the force of detachment and work of adhesion are recommended for applications on skin tissue. The Doxorubicin was loaded into the hydrogels and the drug was released by diffusion for all the resulting hydrogels, with small contributions from the hydrogel networks' relaxation. Doxorubicin-loaded hydrogels are efficient on keratinocytes tumor cells, the sustained released drug interrupting the cells' division and inducing cell apoptosis; we recommend the obtained materials for the topical treatment of cutaneous squamous cell carcinoma.

Cholesterol concentration effect on bilayer membranes and its role in designing efficient liposomal drug delivery systems.

Liposomal drug delivery systems provide a versatile therapeutic platform for treating numerous diseases. Cholesterol, as a common component of many liposomal drug delivery systems, plays a crucial role in enhancing mechanical strength and decreasing the permeability of biomembranes. However, the ratio required for a proper formulation is poorly recognized. In this study, all-atom molecular dynamics simulations are performed to characterize the effect of cholesterol concentration in bilayers. To prepare liposomes, we simulate DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine) phospholipid combined with different molar ratios of cholesterol (100, 80-20, 70-30, and 60-40%) in both planar and spherical bilayers. Furthermore, it has been quantified how a range of bilayer properties, including area per lipid, leaflet interdigitation, membrane thickness, and lipid Scd order parameters, are altered by variation in concentrations of lipid and cholesterol. Therefore, the most suitable amount of cholesterol and lipid to prepare stable and controlled drug release vehicles is obtained by screening the lipid and cholesterol ratio arrangement. Compared to membranes without cholesterol, the influence of cholesterol on lipid bilayers is revealed. These results provide a better understanding of the fundamental characteristics of the structure and dynamics of cholesterol-containing membranes. By revealing molecular details of interactions between cholesterol and phospholipids, these simulations accurately represent atomic-level characteristics of the planar and spherical bilayers. The simulations presented here shed light on the workings and limitations of liposomal drug delivery technology and establish a computational framework for the rational design of liposomes in drug delivery systems.

Can We Structure Biomaterials to Spray Well Whilst Maintaining Functionality?

Structured fluid biomaterials, including gels, creams, emulsions and particle suspensions, are used extensively across many industries, including great interest within the medical field as controlled release vehicles to improve the therapeutic benefit of delivered drugs and cells. Colloidal forces within these materials create multiscale cohesive interactions, giving rise to intricate microstructures and physical properties, exemplified by increasingly complex mathematical descriptions. Yield stresses and viscoelasticity, typically arising through the material microstructure, vastly improve site-specific retention, and protect valuable therapeutics during application. One powerful application route is spraying, a convenient delivery method capable of applying a thin layer of material over geometrically uneven surfaces and hard-to-reach anatomical locations. The process of spraying is inherently disruptive, breaking a bulk fluid in successive steps into smaller elements, applying multiple forces over several length scales. Historically, spray research has focused on simple, inviscid solutions and dispersions, far from the complex microstructures and highly viscoelastic properties of concentrated colloidal biomaterials. The cohesive forces in colloidal biomaterials appear to conflict with the disruptive forces that occur during spraying. This review explores the physical bass and mathematical models of both the multifarious material properties engineered into structured fluid biomaterials and the disruptive forces imparted during the spray process, in order to elucidate the challenges and identify opportunities for rational design of sprayable, structured fluid biomaterials.

Influence of ultrasound and enzymatic cross-linking on freeze-thaw stability and release properties of whey protein isolate hydrogel.

This study investigated the effect of ultrasound and enzymatic cross-linking on the freeze-thaw (FT) stability and release properties of whey protein isolate hydrogels. We evaluated the FT stability by the changes in the microstructure, riboflavin retention, syneresis, water holding capacity (WHC), and texture of gels subjected to 3 FT cycles. High-intensity ultrasound (HUS) and transglutaminase (TGase)-mediated cross-linking improved the FT stability of whey protein isolate hydrogels loaded with riboflavin (WPISAR), as demonstrated by a more uniform and denser porous structure, significantly higher riboflavin retention, WHC, and textural properties, and lower syneresis after 3 FT cycles than those of untreated hydrogels. Furthermore, HUS- and TGase-mediated cross-linking decreased protein erosion and swelling ratio of WPISAR in simulated gastrointestinal fluids (SGIF) and reduced the riboflavin release rate in SGIF both with and without the addition of digestive enzymes. After 3 FT cycles, faster riboflavin release occurred due to a more porous structure induced by ice crystal formation compared with their unfrozen counterparts as detected by confocal laser scanning microscopy. High-intensity ultrasound- and TGase-mediated cross-linking alleviated the FT-induced faster riboflavin release rate in SGIF. High-intensity ultrasound- and TGase-treated gel samples showed that both diffusion and network erosion were responsible for riboflavin release regardless of FT. These results suggest that HUS- and TGase-mediated cross-linking improved the FT stability of WPISAR with a high riboflavin retention, and might be a good candidate as a controlled-release vehicle for riboflavin delivery to overcome undesired FT processing.

An injectable supramolecular nanofiber-reinforced chitosan hydrogel with antibacterial and anti-inflammatory properties as potential carriers for drug delivery.

The inherent weak mechanical strength of chitosan physical cross-linking hydrogels (CS hydrogels) limits their applications in biomaterials. Hence, puerarin (PUE) as a self-assembly active small molecule in herbal was introduced in CS hydrogels to fabricate CS/PUE18 composite hydrogels with interpenetrating network structure. The result of rheological measurement showed that storage modulus and loss modulus of CS/PUE18 composite hydrogels were improved by three orders of magnitude, indicating that the introduction of PUE significantly reinforced CS hydrogels. The results of SEM and BET measurement demonstrated that macromolecular chains of CS intertwined with nanofibers of PUE, which caused the network structure of CS/PUE18 composite hydrogels to become denser. XRD patterns and FT-IR spectra verified that the amino groups in CS formed hydrogen bonding with the hydroxyl groups in PUE. Degradation and swelling experiments showed that CS/PUE18 composite hydrogels have pH sensitivity. Moreover, CS/PUE18 composite hydrogels exhibited multi-functionality including injectability, thixotropy, cytocompatibility, antibacterial and anti-inflammatory properties. The release behavior of berberine chloride hydrate (BCH) and PUE from the resultant CS/PUE18 composite hydrogels have pH dependence. These results revealed that injectable CS/PUE18 composite hydrogels with dual antibacterial and anti-inflammatory properties could be potential delivery vehicles for sustained and controlled release.

Controlled release of 5-Fluorouracil by a novel L-Lysine based polyesterurethane material synthesized from Epoxide and CO2 via a novel dicopper salen catalyst

Controlled release of anticancer drug 5-Fluorouracil by several delivery systems are known including porous polymeric materials. Herein we report a novel L-lysine based porous polyesterurethane material 1 which acts as a controlled release vehicle for 5-Fluorouracil. Polyesterurethane material 1 was synthesized from a green isocyanate and phosgene free synthetic route involving conversion of epoxide 2-(phenoxymethyl)oxirane and CO2 to cyclic carbonate 2 followed by ring opening with an amino acid L-Lysine to a bishydroxy compound 3 under green aqueous reaction condition. The bishydroxy compound 3 was subsequently reacted with 0.66 equivalent of trimesyl chloride in presence of triethyl amine to get the polyesterurethane material 1. The polyesterurethane material 1 was characterized via NMR, IR and MALDI analysis. From the SEM image of the polyesterurethane 1 and 5-Fluorouracil encapsulated polyesterurethane 1 it is evident that material 1 remain with porous topology which is filled by 5-Fluorouracil that is further evidenced by EDX spectroscopy with the presence of Fluorine. The controlled release of 5-Fluorouracil from the drug encapsulated 1 was monitored via UV visible spectroscopy at pH 7.4.

Zn/Al Layered double hydroxides nanostructure as effective controlled release vehicle of nicotinic acid for topical applications

The delivery of active ingredients through the human skin is an arduous exercise because of its structural intricacy and outstanding barrier characteristics. Nanotechnological developments have produced advanced delivery systems based on nanomaterials to reinforce the skin's ability to absorb hydrophobic, hydrophilic active ingredients and macromolecules. In this study, inorganic crystalline layered double hydroxides nanostructures (LDH) were used as an advanced release system for nicotinic acid, with skin lightening properties. Nicotinic acid was incorporated into the interlayer space of Zn/Al LDH, by co-precipitation method to develop LDH hybrids. The LDH hybrids were characterized using FTIR, XRD, TGA, and SEM. Intercalation of nicotinic acid in the interlayer space of Zn/Al LDH was ascertained by the shifting of the basal spacing d (003) reflection in the XRD pattern, to lower angles (2θ). FTIR spectra of the Zn/Al LDH hybrids displayed the absorption frequencies of nicotinic acid that indicated the presence of nicotinic acid within the LDH matrix. TGA showed that nicotinic acid intercalated in the interlayer of LDH exhibited better thermal stability than the free form of nicotinic acid. In vitro release experiments revealed controlled and pH-responsive release of nicotinic acid from Zn/Al LDH. Transdermal permeation studies employing Franz- diffusion cells demonstrated that the formulation containing nicotinic acid-intercalated Zn/Al LDH considerably enhanced the penetration of nicotinic acid compared to the formulation containing the free form of nicotinic acid. Thus, Zn/Al LDH has great potential for use as a sustained and controlled release reservoir of nicotinic acid in skin care and other topical applications.

Liposomes: Structure, Biomedical Applications, and Stability Parameters With Emphasis on Cholesterol.

Liposomes are essentially a subtype of nanoparticles comprising a hydrophobic tail and a hydrophilic head constituting a phospholipid membrane. The spherical or multilayered spherical structures of liposomes are highly rich in lipid contents with numerous criteria for their classification, including structural features, structural parameters, and size, synthesis methods, preparation, and drug loading. Despite various liposomal applications, such as drug, vaccine/gene delivery, biosensors fabrication, diagnosis, and food products applications, their use encounters many limitations due to physico-chemical instability as their stability is vigorously affected by the constituting ingredients wherein cholesterol performs a vital role in the stability of the liposomal membrane. It has well established that cholesterol exerts its impact by controlling fluidity, permeability, membrane strength, elasticity and stiffness, transition temperature (Tm), drug retention, phospholipid packing, and plasma stability. Although the undetermined optimum amount of cholesterol for preparing a stable and controlled release vehicle has been the downside, but researchers are still focused on cholesterol as a promising material for the stability of liposomes necessitating explanation for the stability promotion of liposomes. Herein, the prior art pertaining to the liposomal appliances, especially for drug delivery in cancer therapy, and their stability emphasizing the roles of cholesterol.

Improved Gel Properties of Whey Protein-Stabilized Emulsions by Ultrasound and Enzymatic Cross-Linking.

This study investigated the effects of high-intensity ultrasound (HUS) and transglutaminase pretreatment on the gelation behavior of whey protein soluble aggregate (WPISA) emulsions. HUS pretreatment and TGase-mediated cross-linking delayed the onset of gelation but significantly increased (p < 0.05) the gel firmness (G′) both after gel formation at 25 °C and during storage at 4 °C. The frequency sweep test indicated that all gels had a similar frequency dependence at 4 and 25 °C, and the elasticity and viscosity of the WPISA-stabilized emulsion gel were significantly enhanced by HUS pretreatment and TGase-mediated cross-linking (p < 0.05). HUS and TGase-mediated cross-linking greatly improved the textural properties of WPISA-stabilized emulsion gels, as revealed by their increases in gel hardness, cohesiveness, resilience, and chewiness. HUS pretreatment and TGase-mediated cross-linking significantly increased the water-holding capacity but decreased the swelling ratios of the gels (p < 0.05). Interactive force analysis confirmed that noncovalent interactions, disulfide bonds, and TGase-induced covalent cross-links were all involved in the formation of gel networks. In conclusion, the combination of HUS and TGase-mediated cross-linking were beneficial for improving the gelation properties of WPISA-stabilized emulsion as a controlled release vehicle for potential food industrial applications.

Accelerated in vitro release testing method for a long-acting peptide-PLGA formulation

Poly (lactic-co-glycolic acid) (PLGA), a biocompatible and biodegradable polymer, is one of the most commonly used vehicles for controlled-release (CR) implantable dosage forms. Drug molecules formulated in such CR vehicles are released slowly over an extended period of time – often months to years – posing challenges for batch release and quality control testing. Thus, reliable and reproducible accelerated testing methods are required to bridge this gap during early formulation development. This work describes the development of an accelerated in vitro release testing method to predict the real-time in vitro release of a synthetic peptide from a 6-month CR PLGA implant formulation. While accelerated methods have been previously reported for PLGA-based formulations, this work describes a unique case of an aggregation-prone peptide, which required careful attention to the impact of different conditions on both release kinetics and peptide stability. This method describes a suitable combination of release conditions that could help in understanding the release profiles of such peptides prone to aggregation. Parameters including pH, buffer species, temperature, and addition of organic co-solvents and surfactants were evaluated separately and in combination for their ability to achieve complete peptide release within 2 weeks while accurately recapitulating release rate, profile and peptide stability. The accelerated release method that gave the best agreement with real-time release was a mixed media of co-solvent (5% tetrahydrofuran), surfactant (5% TritonX-100) and elevated temperature (50 °C) in a neutral buffer (PBS pH 7.4). This optimized accelerated release method achieved complete release of the peptide load within 14–21 days compared to 3- to 6-months of real-time release and could discriminate critical differences in release behavior between different CR formulations to guide formulation and process development.

Vaccine implants: current status and recent advancements.

Implants have long been used in the field of drug delivery as controlled release vehicles and are now being investigated as single-shot vaccine technologies. Implants have shown great promise, minimizing the need for multiple immunizations while stimulating potent immune responses with reduced doses of vaccine. Synchronous release of vaccine components from implants over an appropriate period of time is important in order to avoid issues including immune tolerance, sequestration or deletion. Traditionally, implants require surgical implantation and removal, which can be a barrier to their widespread use. Degradable and in situ implants are now being developed that can be administered using minimally invasive subcutaneous or intramuscular injection techniques. Injectable hydrogels remain the most commonly studied approach for sustained vaccine delivery due to their ease of administration and tunable degradation properties. Despite exciting advancements in the field of vaccine implants, few technologies have progressed to clinical trials. To increase the likelihood of clinical translation of vaccine implants, strategic testing of disease-relevant antigens in appropriate species is essential. In this review, the significance of vaccine implants and the different types of implants being developed to deliver vaccines are discussed.

Development of electrospun polymer scaffolds for the localized and controlled delivery of siponimod for the management of critical bone defects.

Sphingosine 1-phosphate (S1P) receptor modulators can influence bone regeneration owing to their positive impact on osteoblast differentiation and neovascularisation. While previous studies have utilised non-specific S1P and fingolimod, this study aims to design and characterise a controlled release vehicle to deliver the specific S1P1 & 5 receptor modulator siponimod and test its effectiveness in rat critical cranial defects. Electrospun scaffolds of poly lactide-co-glycolide (PLGA) were loaded with siponimod at drug:polymer mass ratios of 0.5:100 to 2:100. Where indicated, collagen was co-spun at a collagen:polymer mass ratio of 2:100. Thereafter, scaffolds underwent in vitro physicochemical characterisation and in vivo assessment using a rat cranial defect model. Drug-loaded scaffolds showed controlled release of siponimod, -cytocompatibility with endothelial and osteoblast cells in vitro, and furthermore, showed that released siponimod stimulated osteoblast differentiation and endothelial cell migration. The in vivo cranial defect repair study showed regeneration was occurring in the defect, although there was no significant difference in the extent of mineralisation between scaffold experimental groups. To our knowledge, this is the first study investigating siponimod in bone regeneration. In vitro studies confirm a positive impact on key cells involved in bone regeneration, however, the scaffolds did not result in significant repair of critical cranial defects.

Preparation iiand characterization of mucoadhesive microcapsules of paclitaxel

The objective of the present work was to develop paclitaxel encapsulated mucoadhesive microcapsules with an aim to enhance its efficacy and control the drug release in cancer patients. Paclitaxel microcapsules with a coat consisting of sodium alginate and mucoadhesive polymer such as acacia, Carbomer 941, Povidone K-30, Macrogol (PEG 6000) were prepared by ionotropic gelation technique and were evaluated for morphological characters, drug content, loading efficiency, drug–polymer interactions, swelling ratio, mucoadhesive properties and in vitro drug release. The resulting microcapsules were discrete, spherical, and free-flowing with a particle size range of 534 to 822 µm. The microencapsulation efficiency was 45.09–99.83%. The microcapsules prepared with alginate along with macrogol (F4M) have exhibited good mucoadhesive property in the in vitro wash off test. The swelling ratio of microcapsules was enhanced with increased alginate concentration and the formulation (F4) showed highest swelling index of 2666. Paclitaxel release from these mucoadhesive microcapsules was slow and extended over a period of 6 h and further depends upon the concentration of the alginate. The percent drug release of alginate-acacia microcapsules (F4Ac) was higher than other formulations in the present study. In conclusion, alginate-acacia mucoadhesive microcapsules could be promising vehicle for oral controlled release of paclitaxel.

SCIDOT-25. ENHANCING THE EFFICACY OF DRUG RELEASED FROM LOADED FIBRIN GLUE BY PHOTOCHEMICAL INTERNALIZATION (PCI)

Abstract Although gross total resection of gliomas is often possible with current available techniques, almost all tumors recur due to the infiltrative nature of these tumors. Infiltrative tumor cells in normal brain are consequently protected by the blood brain barrier (BBB), greatly reducing the efficacy of chemotherapy. Localized per-operative methods of slow-release drug delivery, that bypass the BBB altogether, are therefore of considerable interest. Fibrin glue (FG) is a FDA approved compound often used during surgery. FG loaded with drugs has been studied as a localized controlled release vehicle but the quantity and release kinetics attainable for some drugs using FG are often inadequate. Photochemical internalization (PCI) has been demonstrated to significantly enhance the efficacy of several chemo-theraputic agents such as bleomycin (BLM) and doxorubicin (DOX). In particular PCI of BLM has been shown to be effective in sterilizing the tumor bed after marginal cytoreductive surgery. We have evaluated the ability of PCI to enhance the ability of BLM and DOX, released from loaded FG, to inhibit the growth of multi-cell glioma spheroids in vitro. Spheroid growth was monitored for 14 days. The results of the present study show that drug was released for up to 72 hours. The growth inhibition caused by either BLM or DOX was significantly enhanced by PCI. The photosensitizer AlPcS2a could also be loaded and released from FG allowing local delivery at the tumor site.

Folic acid-conjugated magnetic ordered mesoporous carbon nanospheres for doxorubicin targeting delivery.

Folic acid-conjugated magnetic ordered mesoporous carbon nanospheres (FA-MOMCNs) are developed as a targeting delivery vehicle of doxorubicin (DOX) in this work. Investigations on DOX loading mechanism show that the loading capacity of FA-MOMCNs is up to 577.12 mg g-1 by means of both physical porous adsorption and covalent interactions, and the pH-dependent drug release is achieved. Excellent biocompatibility of FA-MOMCNs with blood and cells is confirmed by hemolysis and cytotoxicity assays. With the assistance of effective passive and active targeting, DOX-loading FA-MOMCNs can be readily internalized into cancer cell, where the carried DOX can be efficiently released in the acidic microenvironment of the cancer cell for its proliferation inhibition. This controlled release and targeting vehicle of DOX makes it possible to reduce the toxic effect to normal tissues during circulation in the body and is promising for highly efficient chemotherapy.