Drug Release Studies Research Articles

Coated Microneedle System for Delivery of Clotrimazole in Deep-Skin Mycoses.

Mycoses of the skin are infectious diseases caused by fungal microorganisms that are generally treated with topical agents. However, such therapy is often ineffective and has to be supported by oral use of active substances, which, in turn, can cause many side effects. A good alternative for the treatment of deep-skin mycoses seems to be microneedles (MNs). The aim of this research was to fabricate and evaluate the properties of innovative MNs coated with a hydrogel as potential carriers for clotrimazole (CLO) in the treatment of deep fungal skin infections. A 3D printing technique using a photo-curable resin was employed to produce MNs, which were coated with hydrogels using a dip-coating method. Hydrogels were prepared with carbopol EZ-3 Polymer (Lubrizol) in addition to glycerol and triisopropanolamine. Clotrimazole was introduced into the gel as the solution in ethanol or was suspended. In the first step of the investigation, a texture analysis of hydrogels was prepared with a texture analyzer, and the drug release studies were conducted with the use of automatic Franz diffusion cells. Next, the release profiles of CLO for coated MNs were checked. The last part of the investigation was the evaluation of the antifungal activity of the prepared systems, and the inhibition of the growth of Candida albicans was checked with the diffusion and suspended-plate methods. The texture profile analysis (TPA) for the tested hydrogels showed that the addition of ethanol significantly affects the following studied parameters: hardness, adhesiveness and gumminess, causing a decrease in their values. On the other hand, for the gels with suspended CLO, better spreadability was seen compared to gels with dissolved CLO. The presence of the active substance did not significantly affect the values of the tested parameters. In the dissolution study, the results showed that higher amounts of CLO were released for MNs coated with a hydrogel containing dissolved CLO. Also, microbiological tests proved its efficacy against fungal cultures. Qualitative tests carried out using the diffusion method showed that circular zones of inhibition of fungal growth on the plate were obtained, confirming the hypothesis of effectiveness. The suspension-plate technique confirmed the inhibitory effect of applied CLO on the growth of Candida albicans. From the analysis of the data, the MNs coated with CLO dissolved in hydrogel showed better antifungal activity. All received results seem to be helpful in developing further studies for MNs as carriers of antifungal substances.

Development and Characterization of Thermosensitive and Bioadhesive Ophthalmic Formulations Containing Flurbiprofen Solid Dispersions.

In this study, we aimed to develop thermosensitive and bioadhesive in situ gelling systems containing solid dispersions of flurbiprofen (FB-SDs) using poloxamer 407 (P407) and 188 (P188) for ophthalmic delivery. FB-SDs were prepared with the melt method using P407, characterized by solubility, stability, SEM, DSC, TGA, and XRD analyses. Various formulations of poloxamer mixtures and FB-SDs were prepared using the cold method and P407/P188 (15/26.5%), which gels between 32 and 35 °C, was selected to develop an ophthalmic in situ gelling system. Bioadhesive polymers Carbopol 934P (CP) or carboxymethyl cellulose (CMC) were added in three concentrations (0.2, 0.4, and 0.6% (w/w)). Gelation temperature and time, mechanical properties, flow properties, and viscosity values were determined. The in vitro release rate, release kinetics, and the release mechanism of flurbiprofen (FB) from the ophthalmic formulations were analyzed. The results showed that FB-SDs' solubility in water increased 332-fold compared with FB. The oscillation study results indicated that increasing bioadhesive polymer concentrations decreased gelation temperature and time, and formulations containing CP gel at lower temperatures and in a shorter time. All formulations except F3 and F4 showed Newtonion flow under non-physiological conditions, while all formulations exhibited non-Newtonion pseudoplastic flow under physiological conditions. Viscosity values increased with an increase in bioadhesive polymer concertation at physiological conditions. Texture profile analysis (TPA) showed that CP-containing formulations had higher hardness, compressibility, and adhesiveness, and the gel structure of formulation F4, containing 0.6% CP, exhibited the greatest hardness, compressibility, and adhesiveness. In vitro drug release studies indicated that CP and CMC had no effect below 0.6% concentration. Kinetic evaluation favored first-order and Hixson-Crowell kinetic models. Release mechanism analysis showed that the n values of the formulations were greater than 1 except for formulation F5, suggesting that FB might be released from the ophthalmic formulations by super case II type diffusion. When all the results of this study are evaluated, the in situ gelling formulations prepared with FB-SDs that contained P407/P188 (15/26.5%) and 0.2% CP or 0.2% CMC or 0.4 CMC% (F2, F5, and F6, respectively) could be promising formulations to prolong precorneal residence time and improve ocular bioavailability of FB.

Cefixime loaded bare and functionalized halloysite nanocarriers and their biomedical applications

Effective drug delivery for is the foremost requirement for the complete recovery of the disease. Nanomedicine and nanoengineering has provided so many spaces and ideas for the drug delivery design, whether controlled, targeted, or sustained. Different types of nanocarriers or nanoparticles are aggressively designed for the drug delivery applications. Clay minerals are identified as a one of the potential nanocarrier for the drug delivery. Owing to their biocompatibility and very low cytotoxicity, clay minerals showing effective therapeutic applications. In the present investigation, clay mineral, i.e., Halloysite nano tubes are utilized as a nanocarrier for the delivery of antibiotic cefixime (CFX), a third-generation cephalosporin. The HNT was first functionalized with the sulfuric acid and then further treated with the 3-(aminopropyl)triethoxysilane (APTES). The drug is loaded on three different classifications of HNTs, i.e., Bare-CFX-HNT, Acid-CFX-HNT, and APTES-CFX-HNT and their comparative analysis is established. Different characterization techniques such as X-ray diffractometry (XRD), Fourier transform infra-red (FT-IR), Transmission electron microscopy TEM), Brunauer–Emmett–Teller (BET), adsorption studies, and Thermogravimetric analysis (TGA) were performed to evaluate their chemical, structural, morphological, and thermal properties. TGA confirmed the encapsulation efficiency of Bare-CFX-HNT, Acid-CFX-HNT, and APTES-CFX-HNT as 42.65, 52.19, and 53.43%, respectively. Disk diffusion and MTT assay confirmed that the drug loaded HNTs have potential antibacterial activities and less cytotoxicity. The adsorption capacity of CFX with different HNTs are evaluated and Different adsorption and kinetic models have been discussed. Drug release studies shows that APTES-CFX-HNT showing sustained release of cefixime as compared to Bare-CFX-HNT and Acid-CFX-HNT.

Formulation Development of Medicated Chewing Gum by Direct Compression utilizing the SeDeM Diagram Expert System

The main objective of this study was to prepare and characterize the MCG of Ondan HCl which helps to improve the effectivity of the drug and to investigate the applicability of the SeDeM system for the formulation of MCG. The Ondan HCl was formulated into directly compressed MCG utilizing the SeDeM Diagram Expert System. The MCG was optimized using 32 factorial design. Performance evaluation was carried out by evaluating different parameters. Statistical analysis showed that micromeritic properties were improved after inclusion of appropriate excipient in optimum amount. In-vitro drug release study showed 90.01% drug release whereas ex vivo buccal permeation study exhibited significant drug permeation within 15 min indicating its potential for increasing bioavailability. It was concluded that various characteristics of powder material at pre formulation level can be successfully predicted by SeDeM diagram expert system. The developed medicated chewing gum is more effective than mouth dissolving and conventional tablet formulation.
 Keywords: Ondansetron HCl; Medicated chewing gum; direct compression; SeDeM diagram expert system.

Biocompatible gelatin-coated ferrite nanoparticles: A magnetic approach to advanced drug delivery

Nanotechnology has transformed drug delivery, offering opportunities to enhance treatment outcomes while minimizing adverse effects. This study focuses on gelatin-coated cobalt and manganese ferrite nanoparticles for potential drug delivery applications. The synthesis involved a co-precipitation method, and the nanoparticles were characterized using various techniques, including X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, and vibrating sample magnetometer (VSM). Results revealed stable structures, distinct chemical features introduced by gelatin coating, and unique magnetic properties. The hemolysis assay demonstrated reduced hemolytic activity with gelatin coating, enhancing biocompatibility. Drug release studies indicated differential release profiles, with gelatin-coated cobalt ferrite exhibiting higher drug release compared to gelatin-coated manganese ferrite. The Higuchi model supported diffusion-controlled drug release for gelatin-coated cobalt ferrite. These findings suggest the potential of gelatin-coated ferrite nanoparticles for controlled and targeted drug delivery, highlighting their significance in advancing nanomedicine.

Application of ultrasound-assisted compression and 3D-printing semi-solid extrusion techniques to the development of sustained-release drug delivery systems based on a novel biodegradable aliphatic copolyester

The purpose of this study was to investigate the ability of two advanced hot-processing technologies, Ultrasound-Assisted Compression (USAC) and 3D-printing Semi-solid Extrusion (SSE), to manufacture sustained-release drug delivery systems based on a novel biodegradable aliphatic copolyester. The copolymer was synthesized from ω-pentadecalactone (PDL), 1,4-cyclohexanedimethanol (CHDM) and dimethyl succinate (DMS) (monomer ratio PDL/CHDM/DMS 70/30/30) by enzymatic ring opening polymerization and two-step melt polycondensation processes and has a random microstructure, a high molecular weight (107,100 g mol−1) and a relatively low melting point (∼65 °C). The antibacterial agent metronidazole (MTZ) was chosen as model drug and binary physical mixtures copolymer:drug were prepared at 90:10 and 70:30 w/w ratios. Thermal analysis studies evidenced that the formulations could be processed below their degradation temperatures. Drug delivery devices with dense and meshed structures were manufactured using USAC and SSE techniques, respectively, with USAC devices exhibiting more reproducible physical properties than the SSE systems. Powder X-ray diffraction and scanning electron microscopy studies showed a partial sintering of the copolyester during USAC processing while MTZ remained mostly crystalline. In contrast, the copolymer melted and the drug underwent some amorphization when processed using SSE. In vitro drug release studies in phosphate buffer (pH 6.8) showed that, after an initial burst release of metronidazole, USAC and SSE devices exhibited a prolonged and/or sustained drug release over 20 days. The initial burst release was dependent on the manufacturing technique and the drug/polymer ratio, being minimized for SSE devices containing 10 wt% MTZ. The whole drug release profiles fitted well to the Peppas-Sahlin model, being drug diffusion the predominant release mechanism. After the burst release, the sustained release period of USAC and SSE devices containing 10 wt% MTZ showed a good fit to the zero-order kinetic model, with faster drug release from the SSE devices due to the larger surface area of their meshed structure. In conclusion, this work demonstrates that processing the aliphatic copolyester by both USAC and SSE technologies provides an attractive strategy to manufacture biodegradable drug delivery systems for long-term release of metronidazole.

Formulation and Characterization of Curcumin 12-Hydroxystearic Acid in Triacetin Organogel for Topical Administration

Background: Curcumin (CUR) and its derivatives have shown a wide variety of biological activities, such as anti-oxidant, anti-inflammatory, anti-tumor, antimicrobial and antiparasitic effects as well as for the treatment of skin diseases. Due to its physico-chemical limitations such as low aqueous solubility and low bioavailability, we developed curcumin organogel as a topical delivery system to overcome those limitations. The12-hydroxystearic acid (12-HSA) is well known as a low-molecular-weight organogelators (LMOGs) capable of gelling an organic liquid phase. Different concentrations of (12-HSA) in triacetin with 50 mg CUR were gelled and applied for various examinations: tabletop rheology, oil binding capacity, pH measurement, spreadability, in vitro drug release, antibacterial activity and oscillatory rheology studies. The results revealed that the organogels transition temperatures from solid to liquid were greater than the normal body temperature, this helped the organogels keep their shape; they had good spreadability,and the organogels pH levels were within the safe range for the skin . In vitro release data showed that 4% 12HSA+5%CUR +TA (4TA) gave us 100% release after 6 hours. The selected 4TA illustrated good viscoelastic properties in the amplitude sweep test and a frequency-independent as seen in the frequency sweep test. CUR has good antibacterial action against Staphylococcus aureus; Streptococcus pyrogen, Proteus mirabilis, and Escherichia coli, which prevail at the site of wound injury as this pointed out that 4TA organogel can be used for topical wound healing.

A Low Transition Temperature Mixture-based viscosupplementation complemented with celecoxib for osteoarthritis treatment

Viscosupplementation consists of hyaluronic acid (HA) intra-articular injections, commonly applied for osteoarthritis treatment while non-steroidal anti-inflammatory drugs (NSAIDs) are widely administered for pain relief. Here, HA and a NSAID (celecoxib) were combined in a formulation based on a low transition temperature mixture (LTTM) of glycerol:sorbitol, reported to increase celecoxib’s solubility, thus rendering a potential alternative viscosupplement envisioning enhanced therapeutic efficiency. The inclusion of glucosamine, a cartilage precursor, was also studied. The developed formulations were assessed in terms of rheological properties, crucial for viscosupplementation: the parameters of crossover frequency, storage (G’) and loss (G’’) moduli, zero-shear-rate viscosity, stable viscosity across temperatures, and shear thinning behaviour, support viscoelastic properties suitable for viscosupplementation. Additionally, the gels biocompatibility was confirmed in chondrogenic cells (ATDC5). Regarding drug release studies, high and low clearance scenarios demonstrated an increased celecoxib (CEX) release from the gel (6 to 73-fold), compared to dissolution in PBS. The low clearance setup presented the highest and most sustained CEX release, highlighting the importance of the gel structure in CEX delivery. NMR stability studies over time demonstrated the LTTM+HA+CEX (GHA+CEX) gel as viable candidate for further in vivo evaluation. In sum, the features of GHA+CEX support its potential use as alternative viscosupplement.

Enhanced antichemobrain activity of amino acid assisted ferulic acid solid dispersion in adult zebrafish (Danio rerio).

Chemotherapy-induced cognitive impairment (CICI), also known as "chemobrain," is a common side effect of breast cancer therapy which causes oxidative stress and generation of reactive oxygen species (ROS). Ferulic acid (FA), a natural polyphenol, belongs to BCS class II is confirmed to have nootropic, neuroprotective and antioxidant effects. Here, we have developed FA solid dispersion (SD) in order to enhance its therapeutic potential against chemobrain. An amorphous ferulic acid loaded leucin solid dispersion (FA-Leu SD) was prepared by utilizing amino acid through spray-drying technique. The solid-state characterization was carried out via Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and field emission scanning electron microscopy (FE-SEM). Additionally, in-vitro release studies and antioxidant assay were also performed along with in-vivo locomotor, biochemical and histopathological analysis. The physical properties showed that FA-Leu SD so formed exhibited spherical, irregular surface hollow cavity of along with broad melting endotherm as observed from FE-SEM and DSC results. The XRD spectra demonstrated absence of sharp and intense peaks in FA-Leu SD which evidenced for complete encapsulation of drug into carrier. Moreover, in-vitro drug release studies over a period of 5h in PBS (pH 7.4) displayed a significant enhanced release in the first hr (68. 49 ± 5.39%) and in-vitro DPPH assay displayed greater antioxidant potential of FA in FA-Leu SD. Furthermore, the in-vivo behavioral findings of FA-Leu SD (equivalent to 150mg/kg of free FA) exhibited positive results accompanied by in-vivo biochemical and molecular TNF-α showed a significant difference (p < 0.001) vis-à-vis DOX treated group upon DOX + FA-Leu SD. Additionally, histopathological analysis revealed neuroprotective effects of FA-Leu SD together with declined oxidative stress due to antioxidant potential of FA which was induced by anticancer drug doxorubicin (DOX). Overall, the above findings concluded that spray-dried FA-Leu SD could be useful for the treatment of chemotherapy induced cognitive impairment.

Fabrication and Synthesis of Thiococlchicoside Loaded Matrix Type Transdermal Patch.

The goal of this work was to synthesize and fabricate matrix type transdermal patches based on a combination of polymers (Eudragit L100, HPMC and PVP K30), plasticizer and crosslinking agents (propylene glycol and triethyl citrate) and adhesives (Dura Tak 87-6908) to increase Thiocolchicoside (THC) absorption via topical route. This method allows avoidance of first-pass metabolism along with a consistent and extended duration of therapeutic activity. Fabrication and casting of polymeric solutions containing THC was done either in petri plates or through lab coater to get transdermal patches. Finally, the formulated patches were studied for their physicochemical and biological evaluation using scanning electron microscopy, FTIR, DSC, XRD and ex-vivo permeation studies using pig ear skin. FTIR studies confirm that the THC characteristics peaks (carbonyl (Amide I) at 1525.5 cm-1, C=O stretching (tropane ring) at 1664.4 cm-1, Amide II band (N-H stretching) at 3325.9 cm-1, thioether band at 2360.7 cm-1, and OH group stretching band at 3400.2 cm-1) are still present in the polymer mixture even after formulation as a transdermal patch, indicating compatibility among all excipients. While on the other hand, DSC studies confirm endothermic peaks for all the polymers along with THC with the highest enthalpy of 65.979 J/g, which is an indicator of sharp endothermic peak at 198°C, leading to the melting of THC. The percentage drug content and percentage moisture uptake of all the formulation was found in the range of 96 ± 2.04 to 98.56 ± 1.34% and 4.13 ± 1.16 to 8.23 ± 0.90%, respectively. Drug release and release kinetics studies confirm that it is dependent on the composition of individual formulation. All these findings support the possibility of using suitable polymeric composition, as well as proper formulation and manufacturing circumstances, to create a one-of-a-kind technology platform for transdermal drug administration.

Synthesis, Characterization and Drug Release Study of Novel Guided Tissue Regeneration Membranes Containing Drug Loaded Chitosan Nanoparticles

Periodontitis is an inflammatory disease which can cause the destruction of the supporting tissues of the tooth leading to tooth loss. The guided tissue regeneration is considered as a gold standard for its treatment but the re-infection of surgical site limits its overall success. Objective: To synthesize novel monolayer guided tissue regeneration (GTR) membrane containing drug loaded chitosan nanoparticles and to evaluate the drug release from the synthesized GTR membranes. Methods: The chitosan nanoparticles containing ciprofloxacin were synthesized by the ionotropic gelation method and these synthesized nanoparticles were added into chitosan GTR membrane fabricated by the freeze gelation method. For comparison GTR membrane was prepared as a control by freeze gelation method in which the drug was added directly. The prepared membranes were characterized by the SEM and FTIR. The drug release was measured from the membrane samples in the phosphate buffer saline (PBS) at 1, 3, 5, 7 and 9 days. Results: The GTR membrane containing the ciprofloxacin loaded chitosan nanoparticles showed fast drug release as compared to the membrane in which the ciprofloxacin was added directly. Conclusions: The inclusion of antibiotic loaded chitosan nanoparticles can increase the drug release from GTR membrane.

Biopolymeric 3D printed implantable scaffolds as a potential adjuvant treatment for acute post-operative pain management

ABSTRACT Background Pain is characterized as a major symptom induced by tissue damage occurring from surgical procedures, whose potency is being experienced subjectively, while current pain relief strategies are not always efficient in providing individualized treatment. 3D printed implantable devices hold the potential to offer a precise and customized medicinal approach, targeting both tissue engineering and drug delivery. Research design and methods Polycaprolactone (PCL) and PCL – chitosan (CS) composite scaffolds loaded with procaine (PRC) were fabricated by bioprinting. Geometrical features including dimensions, pattern, and infill of the scaffolds were mathematically optimized and digitally determined, aiming at developing structurally uniform 3D printed models. Printability studies based on thermal imaging of the bioprinting system were performed, and physicochemical, surface, and mechanical attributes of the extruded scaffolds were evaluated. The release rate of PRC was examined at different time intervals up to 1 week. Results Physicochemical stability and mechanical integrity of the scaffolds were studied, while in vitro drug release studies revealed that CS contributes to the sustained release dynamic of PRC. Conclusions The printing extrusion process was capable of developing implantable devices for a local and sustained delivery of PRC as a 7-day adjuvant regimen in post-operative pain management.

From Polymeric Nanoformulations to Polyphenols-Strategies for Enhancing the Efficacy and Drug Delivery of Gentamicin.

Gentamicin is an essential broad-spectrum aminoglycoside antibiotic that is used in over 40 clinical conditions and has shown activity against a wide range of nosocomial, biofilm-forming, multi-drug resistant bacteria. Nevertheless, the low cellular penetration and serious side effects of gentamicin, as well as the fear of the development of antibacterial resistance, has led to a search for ways to circumvent these obstacles. This review provides an overview of the chemical and pharmacological properties of gentamicin and offers six different strategies (the isolation of specific types of gentamicin, encapsulation in polymeric nanoparticles, hydrophobization of the gentamicin molecule, and combinations of gentamicin with other antibiotics, polyphenols, and natural products) that aim to enhance the drug delivery and antibacterial activity of gentamicin. In addition, factors influencing the synthesis of gentamicin-loaded polymeric (poly (lactic-co-glycolic acid) (PLGA) and chitosan) nanoparticles and the methods used in drug release studies are discussed. Potential research directions and future perspectives for gentamicin-loaded drug delivery systems are given.

Levofloxacin loaded poly (ethylene oxide)-chitosan/quercetin loaded poly (D,L-lactide-co-glycolide) core-shell electrospun nanofibers for burn wound healing.

This study developed a new burn wound dressing based on core-shell nanofibers that co-deliver antibiotic and antioxidant drugs. For this purpose, poly(ethylene oxide) (PEO)-chitosan (CS)/poly(D,L-lactide-co-glycolide) (PLGA) core-shell nanofibers were fabricated through co-axial electrospinning technique. Antibiotic levofloxacin (LEV) and antioxidant quercetin (QS) were incorporated into the core and shell parts of PEO-CS/PLGA nanofibers, respectively. The drugs could bond to the polymer chains through hydrogen bonding, leading to their steady release for 168h. An in vitro drug release study showed a burst effect followed by sustained release of LEV and QS from the nanofibers due to the Fickian diffusion. The NIH 3T3 fibroblast cell viability of the drug loaded core-shell nanofibers was comparable to that in the control (tissue culture polystyrene) implying biocompatibility of the nanofibers and their cell supportive role. However, there was no significant difference in cell viability between the drug loaded and drug free core-shell nanofibers. According to in vivo experiments, PEO-CS-LEV/PLGA-QS core-shell nanofibers could accelerate the healing process of a burn wound compared to a sterile gauze. Thanks to the synergistic therapeutic effect of LEV and QS, a significantly higher wound closure rate was recorded for the drug loaded core-shell nanofibrous dressing than the drug free nanofibers and control. Conclusively, PEO-CS-LEV/PLGA-QS core-shell nanofibers were shown to be a promising wound healing material that could drive the healing cascade through local co-delivery of LEV and QS to burn wounds.

Triple-Hybrid BioScaffold Based on Silk Fibroin, Chitosan, and nano-Biphasic Calcium Phosphates: Preparation, Characterization of Physiochemical and Biopharmaceutical Properties

Bioscaffolds, which promote cell regeneration and restore tissues’ functions, have emerged as significant need in clinic. The hybrid of several biomaterials in a bioscaffold renders clinically advanced and relevant properties for applications yet add challenges in cost efficiency, production, and clinical investigation. This study proposes a facile and sustainable method to formulate a triple-hybrid bioscaffold based on Vietnamese cocoon origin Silk Fibroin, Chitosan, and nano-Biphasic Calcium Phosphates (nano-BCP) that can be easily molded, has high porosity (55–80%), and swelling capacity that facilitates cell proliferation and nutrient diffusion. Notably, their mechanical properties, in particular compressive strength, can easily be tuned in a range from 50 – 200 kPa by changing the amount of nano-BCP addition, which is comparable to the successful precedents for productive cell regeneration. The latter parts investigate the biopharmaceutical properties of a representative bioscaffold, including drug loading and release studies with two kinds of active compounds, salmon calcitonin and methylprednisolone. Furthermore, the bioscaffold is highly biocompatible as the results of hemocompatibility and hemostasis tests, as well as ovo chick chorioallantoic membrane investigation. The findings of the study suggest the triple-hybrid scaffold as a promising platform for multi-functional drug delivery and bone defect repair.

Abstract 478: Targeted combination nano-drug delivery system to enhance anti-cancer efficacy and reduce side effects

Abstract Background: Colorectal cancer (CRC) is a global health concern, with significant morbidity and mortality. Oxaliplatin (OXL) is a common treatment for CRC but its effectiveness is hampered by side effects, including gastrointestinal and neurotoxic effects. APX3330 exerts anti-angiogenic and neuroprotective effects. It is proposed that the combined use of OXL and APX3330-loaded nanoparticles (NPs) would improve drug delivery to cancer cells with enhanced therapeutic efficacy while reducing side effects of OXL. Methods: We developed dual-loaded NPs containing OXL and APX3330 linked to a cancer targeting monoclonal antibody (NPs+mAb). We characterized the physicochemical properties of the NPs and evaluated their cytotoxicity and drug release using CRC cell lines. In vivo, we assessed their therapeutic efficiency and side effects using an orthotopic CRC mouse model. Results: NPs exhibited an average size of 229±26 nm with a zeta potential of -24.1±2.1 mV. The drug loading and encapsulation efficiency were 3.3±0.2% and 71.9%, respectively. Morphological analysis via scanning electron microscopy confirmed NP structure. In vitro drug release studies showed a slower release profile from NPs compared to free OXL, with a cumulative release of 34% (w/w) after 48 hours. Notably, cytotoxicity evaluation on CT-26 cells revealed a significant reduction in the IC50 for NPs compared to free APX3330 and OXL. In vivo studies demonstrated a remarkable 31% reduction in tumor growth rate in animals treated with NPs+mAb compared to those receiving free forms of OXL and APX3330. Body weight for animals treated with NPs+mAb remained similar to the healthy group, indicating minimal systemic toxicity. Moreover, the length of the colon in healthy organs remained steady compared to animals treated with OXL, which experienced a reduction in colon length. Animals treated with the free form of OXL exhibited diarrhoea, while the stool water content for animals treated with NPs+mAb remained at a similar level as the healthy group, suggesting reduced gastrointestinal side effects. Conclusions: This study demonstrates the potential of NPs with improved retention and encapsulation efficiency for effective drug delivery. Our research validates our novel method for creating NPs with mAb conjugation, enhancing cytotoxicity against CRC cell lines. In conclusion, the designed NPs+mAb formulation improves OXL treatment efficacy, providing targeted delivery of anti-cancer drugs to the tumor site and reducing tumor size while minimizing side effects. Citation Format: Niloufar Rashidi, Majid Davidson, Vasso Apostolopoulos, Mark R. Kelley, Kulmira Nurgali. Targeted combination nano-drug delivery system to enhance anti-cancer efficacy and reduce side effects [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 478.

Levofloxacin loaded chitosan and poly-lactic-co-glycolic acid nano-particles against resistant bacteria: Synthesis, characterization and antibacterial activity

BackgroundWith the global increase in antibacterial resistance, the challenge faced by developing countries is to utilize the available antibiotics, alone or in combination, against resistant bacterial strains. We aimed to encapsulate the levofloxacin (LVX) into polymeric nanoparticles using biodegradable polymers i.e. Chitosan and PLGA, estimating their physicochemical characteristics followed by functional assessment as nanocarriers of levofloxacin against the different resistant strains of bacteria isolated from biological samples collected from tertiary care hospital in Lahore, Pakistan. MethodsLVX-NPs were synthesized using ion gelation and double emulsion solvent-evaporation method employing chitosan (CS) and poly-lactic-co-glycolic acid (PLGA), characterized via FTIR, XRD, SEM, and invitro drug release studies, while antibacterial activity was assessed using Kirby-Bauer disc-diffusion method. ResultsData revealed that the levofloxacin-loaded chitosan nanoparticles showed entrapment efficiency of 57.14% ± 0.03 (CS-I), 77.30% ± 0.08(CS-II) and 87.47% ± 0.08 (CS-III). The drug content, particle size, and polydispersity index of CS-I were 52.22% ± 0.2, 559 nm ± 31 nm, and 0.030, respectively, whereas it was 66.86% ± 0.17, 595 nm ± 52.3 nm and 0.057, respectively for CS-II and 82.65% ± 0.36, 758 nm ± 24 nm and 0.1, respectively for CS-III. The PLGA-levofloxacin nanoparticles showed an entrapment efficiency of 42.80% ± 0.4 (PLGA I) and 23.80% ± 0.4 (PLGA II). The drug content, particle size and polydispersity index of PLGA-I were 86% ± 0.21, 92 nm ± 10 nm, and 0.058, respectively, whereas it was 52.41% ± 0.45, 313 nm ± 32 nm and 0.076, respectively for PLGA-II. The XRD patterns of both polymeric nanoparticles showed an amorphous nature. SEM analysis reflects the circular-shaped agglomerated nanoparticles with PLGA polymer and dense spherical nanoparticles with chitosan polymer. The in-vitro release profile of PLGA-I nanoparticles showed a sustained release of 82% in 120 h and it was 58.40% for CS-III. Both types of polymeric nanoparticles were found to be stable for up to 6 months without losing any major drug content. Among the selected formulations, CS-III and PLGA-I, CS-III had better antibacterial potency against gram+ve and gram-ve bacteria, except for K. pneumonia, yet, PLGA-I demonstrated efficacy against K. pneumonia as per CSLI guidelines. All formulations did not exhibit any signs of hemotoxicity, nonetheless, the CS-NPs tend to bind on the surface of RBCs. ConclusionThese data suggested that available antibiotics can effectively be utilized as nano-antibiotics against resistant bacterial strains, causing severe infections, for improved antibiotic sensitivity without compromising patient safety.

Fast-setting multi-stimuli responsive silk hydrogels tailored with dual network interface

Silk fibroin, a naturally occurring and versatile polymer with broad range of material forms and applications, presents numerous advantages. Notably, hydrogels are noteworthy among these advantages due to their inherent hydrophilicity, biocompatibility, and flexibility. Nevertheless, their practical utility has been hindered by intricate preparation procedures and limited mechanical strength. In this investigation, we introduce a straightforward and cost-effective method for producing a novel silk hydrogel. Subsequent to the hydrogel synthesis, an ethanol treatment was employed to induce the preferential formation of β-sheet conformations. The developed system exhibits rapid gelation (gelation time: 3 min) and non-swelling behavior (swelling ratio = 0.47). This suggests its potential suitability for biomedical devices without imposing strain on adjacent tissues. Conformational rearrangement of polymeric chains induced by ethanol treatment contributed to heightened material crystallinity, resulting in a remarkable 55.9% increase in Young's modulus and a substantial 91.2% enhancement in ultimate tensile strength for the ethanol-treated hydrogels (SF/AG/Gly/Eth) when compared to their non-ethanol-treated counterparts (SF/AG/Gly). Additionally, in-situ biodegradation studies on silk hydrogels confirmed the material's degradability, with a notable 94.75% weight loss within 3 days, following pseudo-second-order kinetics (R2 = 0.991). This degradation is attributed to action of proteolytic enzymes on the amino acid units of silk fibroin, alleviating concerns regarding waste generation. Moreover, these pH and water-responsive hydrogels can be harnessed in the fabrication of intelligent biomedical devices. Further, drug release studies on silk hydrogels showed that both ethanol-treated and non-treated samples displayed sustained drug release following the Korsmeyer−Peppas model, with an entrapment efficiency of 65.6% and 48.2%, respectively.

Exploring Cyclodextrin-Based Nanosponges as Drug Delivery Systems: Understanding the Physicochemical Factors Influencing Drug Loading and Release Kinetics.

Cyclodextrin-based nanosponges (CDNSs) are complex macromolecular structures composed of individual cyclodextrins (CDs) and nanochannels created between cross-linked CD units and cross-linkers. Due to their unique structural and physicochemical properties, CDNSs can possess even more beneficial pharmaceutical features than single CDs. In this comprehensive review, various aspects related to CDNSs are summarized. Particular attention was paid to overviewing structural properties, methods of synthesis, and physicochemical analysis of CDNSs using various analytical methods, such as DLS, PXRD, TGA, DSC, FT-IR, NMR, and phase solubility studies. Also, due to the significant role of CDNSs in pharmaceutical research and industry, aspects such as drug loading, drug release studies, and kinetics profile evaluation of drug-CDNS complexes were carefully reviewed. The aim of this paper is to find the relationships between the physicochemical features and to identify crucial characteristics that are influential for using CDNSs as convenient drug delivery systems.

Formulation and Characterization of Simvastatin-Loaded Nanosponges: An Innovative Technique for Colon-Targeted Drug Delivery

Background:: To enhance the solubility of simvastatin by improving the surface area of the drug particle by preparing nanosponges that are enclosed in a tablet and capsule oral solid dosage forms, which in turn helps maintain the drug's stability. Objective:: The present investigation aimed to develop a simvastatin nanosponge containing Eu-dragit as a polymer with different ratios of drug-to-polymer concentration to increase its solubility and further improve the oral bioavailability by using nanosponges’ formulation technique. Methods:: The emulsion solvent diffusion method was used to prepare simvastatin nanosponges by using Eudragit S 100, Eudragit L 100, and a combination of both in different drug-to-polymer ratios, i.e., 1:0.5, 1:1, 1:1.5, and 1:2. To characterize the conductivity, molecular changes, and size of the prepared nanosponges, a variety of evaluation parameters, including the compressibil-ity index, Hausner's ratio, angle of repose, microscopy, production yield, entrapment efficiency, drug content, in vitro drug release studies, DSC, XRD, FTIR, and SEM were evaluated. Opti-mized formulation was used to prepare colon-targeted tablets and capsules by taking nanosponges equivalent to 20 mg of simvastatin. Results:: The percentage yield, drug content, and entrapment efficiency of the final formulation were observed at 81 ± 0.26%, 92.4%, and 97 ± 0.56%, respectively. The in vitro drug release of the optimized formulations was 91.42 % at 12 hrs. The drug release followed the Peppas model with a super case II transport mechanism. Conclusion:: The use of the nanosponge delivery system increased the solubility of simvastatin seven times, which in turn increased the drug's bioavailability.