Co-emulsified Alginate-Eudragit Nanoparticles: Potential Carriers for Localized and Time-defined Release of Tenofovir in the Female Genital Tract.

This research aimed to explore the possibilities of Eudragit S100 (ES100) and sodium alginate as carriers for tenofovir disoproxil fumarate (TDF) in the female genital tract. Alginate and alginate-ES100 nanoparticles were prepared using the ionic gelation and emulsion/gelation complexation method, respectively. The nanocarriers were tested using morphological, physicochemical, in vitro drug release, and cytotoxicity analyses. In SEM and TEM images, the presence of spherical and uniformly distributed nanoparticles was revealed. The FTIR spectrum showed that alginate and calcium chloride interacted due to ionic bonds linking divalent calcium ions and the -COO- of alginate groups. Alginate and ES100 interacted via the ester C=O amide stretching. The results obtained from XRD and DSC, on the other hand, revealed a favorable interaction between sodium alginate and ES100 polymers, as evidenced by the crystallization peaks observed. Under experimental design analysis and optimization, overall size distribution profiles ranged from 134.9 to 228.0 nm, while zeta potential results showed stable nanoparticles (-17.8 to -38.4 MV). The optimal formulation exhibited a maximum cumulative in vitro release of 72% (pH 4.2) up to 96 h. The cytotoxicity tests revealed the safety of TDF-loaded nanoparticles on vaginal epithelial cells at concentrations of 0.025 mg/mL, 0.5 mg/mL, and 1 mg/mL for 72 h. These results indicated that alginate-ES100 nanoparticles have the potential to preserve and sustain the release of the TDF drug in the FGT. The future goal is to develop a low-dose non-toxic microbicide that can be administered long term in the vagina to cater to both pregnant and non-pregnant HIV patients.

In Vivo Evaluation of Praziquantel-Loaded Solid Lipid Nanoparticles against S. mansoni Infection in Preclinical Murine Models.

This study aimed to develop and assess the long-term stability of drug-loaded solid lipid nanoparticles (SLNs). The SLNs were designed to extend the release profile, overcome the problems of bioavailability and solubility, investigate toxicity, and improve the antischistosomal efficacy of praziquantel. The aim was pursued using solvent injection co-homogenization techniques to fabricate SLNs in which Compritol ATO 888 and lecithin were used as lipids, and Pluronic F127 (PF127) was used as a stabilizer. The long-term stability effect of the PF127 as a stabilizer on the SLNs was evaluated. Dynamic light scattering (DLS) was used to determine the particle size, stability, and polydispersity. The morphology of the SLNs was examined through the use of transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The chemical properties, as well as the mechanical, thermal, and crystal behaviours of SLNs were evaluated using FTIR, ElastoSens Bio2, XRPD, DSC, and TGA, respectively. SLNs with PF127 depicted an encapsulation efficiency of 71.63% and a drug loading capacity of 11.46%. The in vitro drug release study for SLNs with PF127 showed a cumulative release of 48.08% for the PZQ within 24 h, with a similar release profile for SLNs' suspension after 120 days. DLS, ELS, and optical characterization and stability profiling data indicate that the addition of PF127 as the surfactants provided long-term stability for SLNs. In vitro cell viability and in vivo toxicity evaluation signify the safety of SLNs stabilized with PF127. In conclusion, the parasitological data showed that in S. mansoni-infected mice, a single (250 mg/kg) oral dosage of CLPF-SLNs greatly improved PZQ antischistosomal efficacy both two and four weeks post-infection. Thus, the fabricated CLPF-SLNs demonstrated significant efficiency inthe delivery of PZQ, and hence are a promising therapeutic strategy against schistosomiasis.

Advanced Strategies for Tissue Engineering in Regenerative Medicine: A Biofabrication and Biopolymer Perspective.

Tissue engineering is known to encompass multiple aspects of science, medicine and engineering. The development of systems which are able to promote the growth of new cells and tissue components are vital in the treatment of severe tissue injury and damage. This can be done through a variety of different biofabrication strategies including the use of hydrogels, 3D bioprinted scaffolds and nanotechnology. The incorporation of stem cells into these systems and the advantage of this is also discussed. Biopolymers, those which have a natural original, have been particularly advantageous in tissue engineering systems as they are often found within the extracellular matrix of the human body. The utilization of biopolymers has become increasing popular as they are biocompatible, biodegradable and do not illicit an immune response when placed into the body. Tissue engineering systems for use with the eye are also discussed. This is of particular interest as the eye is known as an immune privileged site resulting in an extremely limited ability for natural cell regeneration.

Bioplatform Fabrication Approaches Affecting Chitosan-Based Interpolymer Complex Properties and Performance as Wound Dressings.

Chitosan can form interpolymer complexes (IPCs) with anionic polymers to form biomedical platforms (BMPs) for wound dressing/healing applications. This has resulted in its application in various BMPs such as gauze, nano/microparticles, hydrogels, scaffolds, and films. Notably, wound healing has been highlighted as a noteworthy application due to the remarkable physical, chemical, and mechanical properties enabled though the interaction of these polyelectrolytes. The interaction of chitosan and anionic polymers can improve the properties and performance of BMPs. To this end, the approaches employed in fabricating wound dressings was evaluated for their effect on the property-performance factors contributing to BMP suitability in wound dressing. The use of chitosan in wound dressing applications has had much attention due to its compatible biological properties. Recent advancement includes the control of the degree of crosslinking and incorporation of bioactives in an attempt to enhance the physicochemical and physicomechanical properties of wound dressing BMPs. A critical issue with polyelectrolyte-based BMPs is that their effective translation to wound dressing platforms has yet to be realised due to the unmet challenges faced when mimicking the complex and dynamic wound environment. Novel BMPs stemming from the IPCs of chitosan are discussed in this review to offer new insight into the tailoring of physical, chemical, and mechanical properties via fabrication approaches to develop effective wound dressing candidates. These BMPs may pave the way to new therapeutic developments for improved patient outcomes.

Lipid-drug conjugates and associated carrier strategies for enhanced antiretroviral drug delivery.

Mortality rate of patients infected with HIV-1 has been significantly reduced by using HAART. However, the virus to date has not been eradicated. Transmission of HIV-1 infection through sexual intercourse remains an ongoing challenge, with increased risk of infection occurring in women. Interestingly, ARV drugs can be chemically linked with lipids to produce lipid-drug conjugates (LDCs). This alters pharmacokinetic properties of ARV drugs and thereby resulting in improved effectiveness. Although LDCs can be administered without a delivery carrier, they are usually incorporated into suitable delivery systems such as lipid nanoparticles, polymeric nanoparticles, micelles, liposomes, emulsions, and carbon nanotubes. Given that LDCs have the potential to improve oral bioavailability, lipophilicity, toxicity, and drug targeting, it is of our great interest to review strategies of lipid-drug conjugation together with their delivery systems for enhanced antiretroviral efficacy.

Dexamethasone-Loaded, PEGylated, Vertically Aligned, Multiwalled Carbon Nanotubes for Potential Ischemic Stroke Intervention.

The complete synthesis, optimization, purification, functionalization and evaluation of vertically aligned multiwalled carbon nanotubes (VA-MWCNTs) was reported for potential application in dexamethasone delivery to the ischemic brain tissue. The conditions for high yield were optimized and carbon nanotubes functionalized and PEGylated prior to dexamethasone loading. Morphological changes were confirmed by SEM and TEM. Addition of functional groups to MWCNTs was demonstrated by FTIR. Thermal stability reduced following MWCNTs functionalization as demonstrated in TGA. The presence of carbon at 2θ of 25° and iron at 2θ of 45° in MWCNTs was illustrated by XRD. Polydispersive index and zeta potential were found to be 0.261 and −15.0 mV, respectively. Dexamethasone release increased by 55%, 65% and 95% in pH of 7.4, 6.5 and 5.5 respectively as evaluated by UV-VIS. The functionalized VA-MWCNTs were demonstrated to be less toxic in PC-12 cells in the concentration range from 20 to 20,000 µg/mL. These findings have demonstrated the potential of VA-MWCNTs in the enhancement of fast and prolonged release of dexamethasone which could lead to the effective treatment of ischemic stroke. More work is under way for targeting ischemic sites using atrial natriuretic peptide antibody in stroke rats.

Development of a Novel Polymeric Nanocomposite Complex for Drugs with Low Bioavailability.

Semi-synthetic biopolymer complex (SSBC) nanoparticles were investigated as a potential oral drug delivery system to enhance the bioavailability of a poorly water-soluble model drug acyclovir (ACV). The SSBCs were prepared from cross-linking of hydroxyl groups on hyaluronic acid (HA) with poly(acrylic acid) (PAA) resulting in ether linkages. Thereafter, conjugation of 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) onto HA-PAA was accomplished using a 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS)-promoted coupling reaction. Nanoparticle powders were prepared by spray drying of drug-loaded SSBC emulsions in a laboratory nano spray dryer. The prepared SSBC was characterized by Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), 1H nuclear magnetic resonance (NMR) imaging, and X-ray diffraction (XRD) spectroscopy. The average particle size was found to be 257.92 nm. An entrapment efficiency of 85% was achieved as ACV has enhanced affinity for the hydrophobic inner core of the complex. It was shown that SSBC improved the solubility of ACV by 30% and the ex vivo permeation by 10% compared to the conventional ACV formulation, consequentially enhancing its bioavailability. Overall, this study resulted in the successful preparation of a hybrid chemically conjugated SSBC which has great potential for enhanced oral absorption of ACV with possible tuneable ACV permeability and solubility, producing an "intelligent" nanoenabled drug delivery system.

Synthesis and Evaluation of a Sodium Alginate-4-Aminosalicylic Acid Based Microporous Hydrogel for Potential Viscosupplementation for Joint Injuries and Arthritis-Induced Conditions.

A microporous hydrogel was developed using sodium alginate (alg) and 4-aminosalicylic acid (4-ASA). The synthesized hydrogel was characterized using various analytical techniques such as Fourier transform infrared spectroscopy (FTIR), Carbon-13 nuclear magnetic resonance (13C-NMR), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC). Additonal carboxyl and hydroxyl functional groups of 4-ASA provided significant lubrication and stress-triggered sol-gel transition to the conjugated hydrogel. In addition, cytotoxicity analysis was undertaken on the conjugated hydrogel using human dermal fibroblast-adult (HDFa) cells, displaying non-toxic characteristics. Drug release profiles displaying 49.6% in the first 8 h and 97.5% within 72 h, similar to the native polymer (42.8% in first 8 h and 90.1% within 72 h). Under applied external stimuli, the modified hydrogel displayed significant gelling properties and structure deformation/recovery behaviour, confirmed using rheological evaluation (viscosity and thixotropic area of 8095.3 mPas and 26.23%, respectively). The modified hydrogel, thus, offers great possibility for designing smart synovial fluids as a biomimetic aqueous lubricant for joint-related injuries and arthritis-induced conditions. In addtion, the combination of thixotropy, non-toxicity, and drug release capabilities enables potential viscosupplementation for clinical application.

Outlook on the Application of Metal-Liganded Bioactives for Stimuli-Responsive Release.

Direct metal-liganded bioactive coordination complexes are known to be sensitive to stimuli such as pH, light, ion activation, or redox cues. This results in the controlled release of the bioactive(s). Compared to other drug delivery strategies based on metal complexation, this type of coordination negates a multi-step drug loading methodology and offers customized physiochemical properties through judicious choice of modulating ancillary ligands. Bioactive release depends on simple dissociative kinetics. Nonetheless, there are challenges encountered when translating the pure coordination chemistry into the biological and physiological landscape. The stability of the metal-bioactive complex in the biological milieu may be compromised, disrupting the stimuli-responsive release mechanism, with premature release of the bioactive. Research has therefore progressed to the incorporation of metal-liganded bioactives with established drug delivery strategies to overcome these limitations. This review will highlight and critically assess current research interventions in order to predict the direction that pharmaceutical scientists could pursue to arrive at tailored and effective metal-liganded bioactive carriers for stimuli-responsive drug release.

Synthesis, Comparison, and Optimization of a Humic Acid-Quat10 Polyelectrolyte Complex by Complexation-Precipitation versus Extrusion-Spheronization.

A novel humic acid and polyquaternium-10 polyelectrolyte complex (PEC) was synthesized utilizing two methods and the solubility and permeability of efavirenz (EFV) were established. Complexation-precipitation and extrusion-spheronization were used to synthesize and compare the drug-loaded PECs. The chemical integrity, thermo-mechanical differences, and morphology between the drug-loaded PECs produced by the two methods were assessed by attenuated total reflectance-Fourier transform infrared, differential scanning calorimetry, and SEM. The extent of drug solubilization was determined using the saturation solubility test while the biocompatibility of both PECs was confirmed by cytotoxicity studies on human adenocarcinoma cells (caco2). Bio-relevant media was used for the solubility and permeability analysis of the optimized PEC formulations for accurate assessment of formulation performance. Ritonavir (RTV) was loaded into the optimized formulation to further corroborate the impact of the PEC on the solubility and permeability properties of a poorly soluble and poorly permeable drug. The optimized EFV-loaded PEC and the RTV-loaded PEC exhibited 14.16 ± 2.81% and 4.39 ± 0.57% increase in solubility, respectively. Both PECs were compared to currently marketed formulations. Intestinal permeation results revealed an enhancement of 61.24 ± 6.92% for EFV and 38.78 ± 0.50% for RTV. Although both fabrication methods produced PECs that enhanced the solubility and permeability of the model Biopharmaceutics Classification System Class II and IV drugs, extrusion-spheronization was selected as most optimal based on the higher solubility and permeability improvement and the impact on caco2 cell viability.

Development of a Gastric Absorptive, Immediate Responsive, Oral Protein-Loaded Versatile Polymeric Delivery System.

A multifunctional platform to deliver three diverse proteins of insulin, interferon beta (INF-ß) and erythropoietin (EPO), using a novel copolymeric microparticulate system of TMC-PEGDMA-MAA, was synthesised as an intelligent pH-responsive 2-fold gastric and intestinal absorptive system. Physiochemical and physicomechanical studies proved the degree of crystallinity that supported the controlled protein delivery of the microparticulate system. The copolymer was tableted before undertaking in vitro and in vivo analysis. After 2.5 h in simulated gastric fluid (SGF), insulin showed a fractional release of 3.2% in comparison to simulated intestinal fluid (SIF), in which a maximum of 83% of insulin was released. Similarly, INF-ß and EPO released 3 and 9.7% in SGF and a maximum of 74 and 81.3% in SIF, respectively. In vivo studies demonstrated a significant decrease in blood glucose by 54.19% within 4 h post-dosing, and the comparator formulation provided 74.6% decrease in blood glucose within the same time period. INF-ß peak bioavailable dose in serum was calculated to be 1.3% in comparison to an SC formulation having a peak concentration of 0.9%, demonstrating steady-state release for 24 h. EPO-loaded copolymeric microparticles had a 1.6% peak bioavailable concentration, in comparison to the 6.34% peak concentration after 8 h from the SC comparator formulation.

A Review of Injectable Polymeric Hydrogel Systems for Application in Bone Tissue Engineering.

Biodegradable, stimuli-responsive polymers are essential platforms in the field of drug delivery and injectable biomaterials for application of bone tissue engineering. Various thermo-responsive hydrogels display water-based homogenous properties to encapsulate, manipulate and transfer its contents to the surrounding tissue, in the least invasive manner. The success of bioengineered injectable tissue modified delivery systems depends significantly on their chemical, physical and biological properties. Irrespective of shape and defect geometry, injectable therapy has an unparalleled advantage in which intricate therapy sites can be effortlessly targeted with minimally invasive procedures. Using material testing, it was found that properties of stimuli-responsive hydrogel systems enhance cellular responses and cell distribution at any site prior to the transitional phase leading to gelation. The substantially hydrated nature allows significant simulation of the extracellular matrix (ECM), due to its similar structural properties. Significant current research strategies have been identified and reported to date by various institutions, with particular attention to thermo-responsive hydrogel delivery systems, and their pertinent focus for bone tissue engineering. Research on future perspective studies which have been proposed for evaluation, have also been reported in this review, directing considerable attention to the modification of delivering natural and synthetic polymers, to improve their biocompatibility and mechanical properties.

Design of Chitosan-Coated, Quercetin-Loaded PLGA Nanoparticles for Enhanced PSMA-Specific Activity on LnCap Prostate Cancer Cells.

Nanoparticles are designed to entrap drugs at a high concentration, escape clearance by the immune system, be selectively taken up by cancer cells, and release bioactives in a rate-modulated manner. In this study, quercetin-loaded PLGA nanoparticles were prepared and optimized to determine whether coating with chitosan would increase the cellular uptake of the nanoparticles and if the targeting ability of folic acid as a ligand can provide selective toxicity and enhanced uptake in model LnCap prostate cancer cells, which express high levels of the receptor prostate-specific membrane antigen (PSMA), compared to PC-3 cells, that have relatively low PSMA expression. A design of experiments approach was used to optimize the PLGA nanoparticles to have the maximum quercetin loading, optimal cationic charge, and folic acid coating. We examined the in vitro release of quercetin and comparative cytotoxicity and cellular uptake of the optimized PLGA nanoparticles and revealed that the targeted nano-system provided sustained, pH-dependent quercetin release, and higher cytotoxicity and cellular uptake, compared to the non-targeted nano-system on LnCap cells. There was no significant difference in the cytotoxicity or cellular uptake between the targeted and non-targeted nano-systems on PC-3 cells (featured by low levels of PSMA), pointing to a PSMA-specific mechanism of action of the targeted nano-system. The findings suggest that the nano-system can be used as an efficient nanocarrier for the targeted delivery and release of quercetin (and other similar chemotherapeutics) against prostate cancer cells.

A Closed Loop Stimuli-Responsive Concanavalin A-Loaded Chitosan-Pluronic Hydrogel for Glucose-Responsive Delivery of Short-Acting Insulin Prototyped in RIN-5F Pancreatic Cells.

The optimal treatment of diabetes (in particular, type 1 diabetes-T1D) remains a challenge. Closed-loop systems (implants/inserts) provide significant advantages for glucose responsivity and providing real-time sustained release of rapid-acting insulin. Concanavalin A (ConA), a glucose affinity agent, has been used to design closed-loop insulin delivery systems but not without significant risk of leakage of ConA from the matrices and poor mechanical strength of the hydrogels impacting longevity and control of insulin release. Therefore, this work focused on employing a thermoresponsive co-forming matrix between Pluronic F-127 (PL) and structurally robust chitosan (CHT) via EDC/NHS coupling (i.e., covalent linkage of -NH2 from CHT and ConA to the -COOH of PL). The system was characterized for its chemical structure stability and integrity (FTIR, XRD and TGA), injectability, rheological parameters and hydrogel morphology (Texture Analysis, Elastosens TM Bio2 and SEM). The prepared hydrogels demonstrated shear-thinning for injectability with a maximum force of 4.9 ± 8.3 N in a 26G needle with sol-gel transitioning from 25 to 38 °C. The apparent yield stress value of the hydrogel was determined to be 67.47 Pa. The insulin loading efficiency within the hydrogel matrix was calculated to be 46.8%. Insulin release studies revealed glucose responsiveness in simulated glycemic media (4 and 10 mg/mL) over 7 days (97%) (305 nm via fluorescence spectrophotometry). The MTT studies were performed over 72 h on RIN-5F pancreatic cells with viability results >80%. Results revealed that the thermoresponsive hydrogel is a promising alternative to current closed-loop insulin delivery systems.

Design and Evaluation of Composite Magnetic Iron-Platinum Nanowires for Targeted Cancer Nanomedicine.

The purpose of the study was to synthesize and investigate the influence of geometrical structure, magnetism, and cytotoxic activity on core-shell platinum and iron-platinum (Fe/Pt) composite nanowires (NWs) for potential application in targeted chemotherapeutic approaches. The Pt-NWs and Fe/Pt composite NWs were synthesized via template electrodeposition, using anodic aluminum oxide (AAO) membranes. The Fe/Pt composite NWs (Method 1) was synthesized using two electrodeposition steps, allowing for greater control of the diameter of the NW core. The Fe/Pt composite NWs (Method 2) was synthesized by pulsed electrodeposition, using a single electrolytic bath. The properties of the synthesized NWs were assessed by high-resolution transmission electron microscopy (HRTEM), Raman spectroscopy, powder X-ray diffraction (XRD), inductively coupled plasma-optical emission spectrometry (ICP-OES), vibrating-sample magnetometry (VSM), and surface charge (zeta potential). A microscopy image analysis of the NWs revealed the presence of high-aspect-ratio NWs with nominal diameters of 40-50 nm and lengths of approximately <4 µm. The obtained powder XRD patterns confirmed the presence of a polycrystalline structure for both Pt NWs and Fe/Pt composite NWs. The potential utility of the synthesized NW nanoplatforms for anticancer activity was investigated using Tera 1 cells and Mouse 3T3 cells. Pt-NWs displayed modest cytotoxic activity against Tera 1 cells, while the Fe/Pt composite NWs (both Methods 1 and 2) demonstrated enhanced cytotoxic activity compared to the Pt-NWs on Tera 1 cells. The Fe/Pt composite NWs (Method 1) displayed ferromagnetic behavior and enhanced cytotoxic activity compared to Pt-NWs on Tera 1 cells, thus providing a sound basis for future magnetically targeted chemotherapeutic applications.

Development of Stable Nano-Sized Transfersomes as a Rectal Colloid for Enhanced Delivery of Cannabidiol.

Current cannabidiol (CBD) formulations are challenged with unpredictable release and absorption. Rational design of a rectal colloid delivery system can provide a practical alternative. In this study the inherent physiochemical properties of transferosomes were harnessed for the development of a nano-sized transfersomes to yield more stable release, absorption, and bioavailability of CBD as a rectal colloid. Transfersomes composed of soya lecithin, cholesterol, and polysorbate 80 were synthesized via thin film evaporation and characterized for size, entrapment efficiency (%), morphology, CBD release, ex vivo permeation, and physicochemical stability. The optimized formulation for rectal delivery entrapped up to 80.0 ± 0.077% of CBD with a hydrodynamic particle size of 130 nm, a PDI value of 0.285, and zeta potential of -15.97 mV. The morphological investigation via SEM and TEM revealed that the transfersomes were spherical and unilamellar vesicles coinciding with the enhanced ex vivo permeation across the excised rat colorectal membrane. Furthermore, transfersomes improved the stability of the encapsulated CBD for up to 6 months at room temperature and showed significant promise that the transfersomes promoted rectal tissue permeation with superior stability and afforded tunable release kinetics of CBD as a botanical therapeutic with inherent poor bioavailability.

In Vivo Evaluation of an Antibody-Functionalized Lipoidal Nanosystem for Schistosomiasis Intervention.

This study employed nanotechnological techniques to design and develop a praziquantel nanoliposomal (NLP) system and surface-functionalized the NLP with anti-calpain antibody (anti-calpain-NLP) for targeted praziquantel (PZQ) delivery in the treatment of schistosomiasis. Anti-calpain-NLPs were prepared and validated for their physicochemical parameters, in vitroand in vivotoxicity, drug entrapment efficiency (DEE), drug loading capacity (DLC), drug release, and parasitological cure rate. The particle sizes for the formulated nanoliposomes ranged from 88.3 to 92.7 nm (PDI = 0.17-0.35), and zeta potential ranged from -20.2 to -31.9 mV. The DLC and DEE ranged from 9.03 to 14.16 and 92.07 to 94.63, respectively. The functionalization of the nanoliposome surface was stable, uniform, and spherical. Fourier-transform infrared (FTIR), thermal behavior and X-ray powder diffraction (XRPD) analysis confirmed that the anti-calpain antibody and PZQ were attached to the surface and the nanoliposomes inner core, respectively. The drug sustained release was shown to be 93.2 and 91.1% within 24 h for NLP and anti-calpain-NLP, respectively. In thein vitroanalysis study, the nanoliposome concentrations range of 30 to 120 µg/mL employed revealed acceptable levels of cell viability, with no significant cytotoxic effects on RAW 264.7 murine macrophage as well as 3T3 human fibroblast cells. Biochemical markers and histopathological analysis showed that the formulated nanoliposomes present no or minimal oxidative stress and confer hepatoprotective effects on the animals. The cure rate of the anti-calpain-NLP and PZQ was assessed by parasitological analysis, and it was discovered that treatment with 250 mg/kg anti-calpain-NLP demonstrated greater activity on the total worm burden, and ova count for both the juvenile and adult schistosomes in the intestine and liver of infected mice. The findings so obtained supported the ability of oral anti-calpain-NLP to target young and adult schistosomes in the liver and porto-mesenteric locations, resulting in improved effectiveness of PZQ.

An Oral 3D Printed PLGA-Tocopherol PEG Succinate Nanocomposite Hydrogel for High-Dose Methotrexate Delivery in Maintenance Chemotherapy.

High-dose methotrexate (HDMTX) is one of the chemotherapeutic agents used to treat a variety of cancers in both adults and children. However, the toxicity associated with HDMTX has resulted in the spread of infections and treatment interruption. Further, poor bioavailability due to efflux pump activities mediated by P-glycoprotein has also been linked to poor therapeutic effects of methotrexate following oral administrations. D-α-Tocopheryl poly-ethylene glycol 1000 succinate (TPGS) is known to improve the bioavailability of poorly soluble drugs by inhibiting P-gp efflux activities, thus enhancing cellular uptake. Therefore, to achieve improved bioavailability for MTX, this study aimed to design and develop a novel drug delivery system employing TPGS and a biodegradable polymer, i.e., PLGA, to construct methotrexate-loaded nanoparticles fixated in alginate-gelatine 3D printable hydrogel ink to form a solid 3D printed tablet for oral delivery. The results indicated that high accuracy (>95%) of the 3D printed tablets was achieved using a 25 G needle. In vitro, drug release profiles were investigated at pH 1.2 and pH 7.4 to simulate the gastrointestinal environment. The in vitro release profile displayed a controlled and prolonged release of methotrexate over 24 h. The in silico modeling study displayed P-gp ATPase inhibition, suggesting enhanced MTX absorption from the gastrointestinal site. The 3D-printed hydrogel-based tablet has the potential to overcome the chemotherapeutic challenges that are experienced with conventional therapies.

A Poly (Caprolactone)-Cellulose Nanocomposite Hydrogel for Transdermal Delivery of Hydrocortisone in Treating Psoriasis Vulgaris.

Psoriasis vulgaris (PV) is a common chronic disease, affecting much of the population. Hydrocortisone (HCT) is currently utilized as a PV treatment; however, it is associated with undesirable side effects. The aim of this research was to create a thermo-responsive nano-hydrogel delivery system. HCT-loaded sorbitan monostearate (SMS)-polycaprolactone (PCL) nanoparticles, encapsulated with thermo-responsive hydrogel carboxymethyl cellulose (CMC), were synthesized by applying the interfacial polymer-deposition method following solvent displacement. The nanoparticles' properties were evaluated employing Differential Scanning Colorimetry, Thermogravimetric Analysis, Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy, Zeta sizer, Ultraviolet/Visual spectroscopy, and cytotoxicity testing. The nanoparticle sizes were 110.5 nm, with polydispersity index of 0.15 and zeta potential of -58.7 mV. A drug-entrapment efficacy of 76% was attained by the HCT-loaded SMS-PCL nanoparticles and in vitro drug-release profiles showed continuous drug release over a period of 24 hrs. Keratinocyte skin cells were treated with HCT-loaded SMS-PCL nanoparticles encapsulated with CMC; the results indicated that the synthesized drug-delivery system was less toxic to the keratinocyte cells compared to HCT. The combined trials and results from the formulation of HCT-loaded SMS-PCL nanoparticles encapsulated with CMC showed evidence that this hydrogel can be utilized as a potentially invaluable formulation for transdermal drug delivery of HCT, with improved efficacy and patient conformity.

Synthesis of a novel monofilament bioabsorbable suture for biomedical applications.

In this research, a novel bioabsorbable suture that is, monofilament and capable of localized drug delivery, was developed from a combination of natural biopolymers that where not previously applied for this purpose. The optimized suture formulation comprised of sodium alginate (6% wt/vol), pectin (0.1% wt/vol), and gelatin (3% wt/vol), in the presence of glycerol (4% vol/vol) which served as a plasticizer. The monofilament bioabsorbable sutures where synthesized via in situ ionic crosslinking in a barium chloride solution (2% wt/vol). The resulting suture was characterized in terms of mechanical properties, morphology, swelling, degradation, drug release, and biocompatibility, in addition to Fourier-transform infrared (FTIR) spectroscopy, Powder X-ray Diffraction (PXRD) and Differential Scanning Calorimetry (DSC) analysis. The drug loaded and non-drug loaded sutures had a maximum breaking strength of 4.18 and 4.08 N, in the straight configuration and 2.44 N and 2.59 N in the knot configuration, respectively. FTIR spectrum of crosslinked sutures depicted Δ9 cm-1 downward shift for the carboxyl stretching band which was indicative of ionic interactions between barium ions and sodium alginate. In vitro analysis revealed continued drug release for 7 days and gradual degradation by means of surface erosion, which was completed by day 28. Biocompatibility studies revealed excellent hemocompatibility and no cytotoxicity. These results suggest that the newly developed bioabsorbable suture meets the basic requirements of a suture material and provides a viable alternative to the synthetic polymer sutures that are currently on the market.