High Drug Loading Research Articles

A pH/Redox Dual‐Responsive Nanocarrier for Hypoxia‐Activated Prodrug and Anticancer Prodrug in Cancer Treatment

AbstractTumor microenvironment heterogeneity (TMH) remains a challenge in cancer treatment. Nanocarrier prodrugs based on small‐molecular drug or macromolecular drug conjugates emerge as an efficient approach for multidrug delivery at tumor sites and activating the prodrugs by endogenous stimuli resulting from TMH. Herein, a redox/pH dual‐sensitive micelle conjugated is developed via disulfide linkage with naphthalimide‐based prodrug (PNA), assigned as PDM to encapsulate hypoxia‐activated prodrug, banoxantrone (AQ4N), for combination therapy. These micelles have several interesting features, including sufficiently stable with less drug release under physiological conditions and dual stimuli‐triggered intracellular release, high drug loading content, and negligible cytotoxicity. More importantly, in vitro cytotoxicity of AQ4N‐loaded PDM micelles exhibits a combinational anticancer efficacy between chemotherapy of PNA and hypoxia‐activated chemotherapy of AQ4N under hypoxic conditions. Moreover, the developed PNA as a new chemotherapeutic drug displays good therapeutic efficiency and fluorescent properties, which can be used for monitoring drug release in real time. This study not only offers an attractive strategy for an effective combination of traditional chemotherapy and hypoxia‐activated chemotherapy, but also provides an important concept to develop dual stimuli‐sensitive prodrug nanoplatform targeting for endogenous TMH.

Ivermectin-Loaded Mesoporous Silica and Polymeric Nanocapsules: Impact on Drug Loading, In Vitro Solubility Enhancement, and Release Performance.

Ivermectin (IVM), a widely used drug for parasitic infections, faces formulation and application challenges due to its poor water solubility and limited bioavailability. Pondering the impact of IVM's high partition coefficient value (log P) on its drug release performance, it is relevant to explore whether IVM nanoencapsulation in organic or inorganic nanoparticles would afford comparable enhanced aqueous solubility. To date, the use of inorganic nanoparticles remains an unexplored approach for delivering IVM. Therefore, here we loaded IVM in mesoporous silica particles (IVM-MCM), as inorganic nanomaterial, and in well-known poly(ε-caprolactone) nanocapsules (IVM-NC). IVM-MCM had a well-organized hexagonal mesoporous structure, reduced surface area, and high drug loading of 10% w/w. IVM-NC had a nanometric mean size (196 nm), high encapsulation efficiency (100%), physicochemical stability as an aqueous dispersion, and drug loading of 0.1% w/w. Despite differing characteristics, both nanoencapsulated forms enhance IVM's aqueous intrinsic solubility compared to a crystalline IVM: after 72 h, IVM-MCM and IVM-NC achieve 72% and 78% releases through a dialysis bag, whereas crystalline IVM dispersion achieves only 40% drug diffusion. These results show distinct controlled release profiles, where IVM-NC provides a deeper sustained controlled release over the whole experiment compared to the inorganic nanomaterial (IVM-MCM). Discussing differences, including drug loading and release kinetics, is crucial for optimizing IVM's therapeutic performance. The study design, combined with administration route plans and safety considerations for humans and animals, may expedite the rational optimization of IVM nanoformulations for swift clinical translation.

Formulation development of methotrexate lipid-based nanogel for treatment of skin cancer

Skin cancer (SC) represents a prevalent malignancy worldwide, characterized by its high drug resistance and limited therapeutic efficacy with conventional treatments. Nanoparticles have emerged as promising vehicles for targeted drug delivery, aiming to overcome these challenges and enhance treatment outcomes. The solid lipid nanocarriers (SLNs) provide improved drug absorption, encapsulation, and controlled release. These SLNs can be customized to meet unique needs, allowing for enhanced targeting, distribution to specific sites, and profiles of sustained release. This study was focused on the development and optimization of methotrexate loaded solid lipid nanoparticles (MTX-SLNs) for improving the drug delivery to the skin cancer therapy. The optimized MTX-SLNs exhibited a particle size of 203 nm, a zeta potential of −8.93 mV, entrapment efficiency of 87%, and drug loading of 62.92%. Subsequently, the optimized MTX-SLNs was incorporated into a gel system containing 1% Carbopol 934, which was further underwent comprehensive characterization, encompassing analysis of rheological properties, texture profile analysis, extrudability and spreadability, as well as uniformity of content. Notably, the dermatokinetic and confocal microscopy evaluations revealed excellent uptake and deposition of MTX-SLNs within the epidermal and dermal layers of the skin. These observations were complemented by the computation of the area under the curve (AUC0–8hr), which demonstrated values of 245.035 and 702.59 for the epidermal and dermal layers, respectively. These findings underscore the tremendous potential of our MTX-SLNs gel formulation as a promising candidate for skin cancer treatment compared to the conventional topical gel therapies, exhibiting superior topical pharmacokinetics, nanometric size, high drug loading capacity, and enhanced efficacy.

Pluronic-coated hydroxypropyl-β-cyclodextrin nanoparticle potentiated chemotherapy on multidrug resistance cancer cells via improved docetaxel loading and P-glycoprotein inhibition

In the pharmaceutical formulation of anticancer drugs, US FDA-approved cyclodextrin (CD) and its derivates have been widely employed. Among them, hydroxypropyl β-cyclodextrin (HPCD) has attracted considerable attention owing to low toxicity, improved water solubility, and enhanced drug absorption; however, HPCD exhibits low drug loading efficiency and poor anticancer efficacy in multidrug-resistant (MDR) cancer cells. Therefore, to improve the drug loading efficiency and simultaneously overcome the MDR effects, we developed docetaxel (DTX)-loaded Pluronic®(PLU)-coated hydroxypropyl-β-cyclodextrin nanoparticles (DTX@PLU/HPCD NPs). We employed a simple nanoprecipitation technique, wherein PLU acted as a P-glycoprotein inhibitor to overcome MDR and an enhancer to achieve high drug loading. The HPCD NPs were coated with PLU (PF127, PP123, and PL81) of varying hydrophilic/lipophilic balance values, and the amount of encapsulated DTX was optimized. The DTX-loaded HPCD formulations (DTX@HPCD NP, DTX@PF127/HPCD NP, and DTX@PP123/HPCD NP) exhibited good stability and facilitated sustained release. The HPCD formulations exerted no cytotoxicity against examined cancer cell lines (HCT15 and SCC 7). DTX@PLU/HPCD NPs exerted potent anticancer effects in vitro. Notably, DTX@PP123/HPCD NPs significantly reduced the tumor volume in a mouse model. Collectively, these results indicate that PLU/HPCD NPs could function as drug carriers to alleviate toxicity and overcome MDR in various cancer models.

The Effect of Polymer-Solvent Interaction on the Swelling of Polymer Matrix Tablets: A Magnetic Resonance Microscopy Study Complemented by Bond Fluctuation Model Simulations.

Polymer matrix tablets are an important drug-delivery system widely used for oral drug administration. Understanding the tablet hydration process, both experimentally and theoretically, is, thus, very important for the development of drug delivery systems that exhibit high drug loading capacity and controlled release potential. In this study, we used magnetic resonance microscopy (MRM) to nondestructively and dynamically analyze the water hydration process of xanthan-based tablets. The swelling process was characterized by well-resolved fronts of erosion, swelling, and penetration. The experimental results were complemented by numerical simulations of the polymer matrix hydration process. In the simulations, the polymer tablet matrix was modeled as an assembly of interacting chains with embedded drug particles, while its hydration process was mediated by interaction with solvent particles. The swelling dynamics were modeled within a Monte Carlo-based bond fluctuation model (BFM) that elegantly accounted for steric and nearest-neighbor interactions. This study provides an efficient experimental-theoretical approach for the study of polymer matrix swelling processes.

A quality-by-design strategic approach for the development of bedaquiline-pretomanid nanoparticles as inhalable dry powders for TB treatment

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (M.tb) and is the second leading cause of death from an infectious disease globally. The disease mainly affects the lungs and forms granulomatous lesions that encapsulate the bacteria, making treating TB challenging. The current treatment includes oral administration of bedaquiline (BDQ) and pretomanid (PTD); however, patients suffer from severe systemic toxicities, low lung drug concentration, and non-adherence. In this study, we developed BDQ-PTD loaded nanoparticles as inhalable dry powders for pulmonary TB treatment using a Quality-by-Design (QbD) approach. The BDQ-PTD combination showed an additive/synergistic effect for M.tb inhibition in vitro, and the optimized drug ratio (1:4) was successfully loaded into polymeric nanoparticles (PLGA NPs). The QbD approach was implemented by identifying the quality target product profile (QTPPs), critical quality attributes (CQAs), and critical process parameters (CPPs) to develop efficient design space for dry powder preparation using spray drying. The three-factorial and three-level Box-Behnken Design was used to assess the effect of process parameters (CPPs) on product quality (CQAs). The Design of Experiments (DoE) analysis showed different regression models for product quality responses and helped optimize process parameters to meet QTPPs. The optimized dry powder showed excellent yield (72 ± 2 % w/w), high drug (BDQ-PTD) loading, low moisture content (<1% w/w), and spherical morphology. Further, aerosolization performance revealed the suitability of powder for deposition in the respiratory airways of the lungs (MMAD 2.4 µm and FPF > 75 %). In conclusion, the QbD approach helped optimize process parameters and develop dry powder with a suitable quality profile for inhalation delivery in TB patients.

Progress of Drug Nanocrystal Self-Stabilized Pickering Emulsions: Construction, Characteristics In Vitro, and Fate In Vivo.

A drug nanocrystal self-stabilized Pickering emulsion (DNSPE) is a novel Pickering emulsion with drug nanocrystals as the stabilizer. As a promising drug delivery system, DNSPEs have attracted increasing attention in recent years due to their high drug loading capacity and ability to reduce potential safety hazards posed by surfactants or specific solid particles. This paper comprehensively reviews the progress of research on DNSPEs, with an emphasis on the main factors influencing their construction, characteristics and measurement methods in vitro, and fate in vivo, and puts forward issues that need to be studied further. The review contributes to the advancement of DNSPE research and the promotion of their application in the field of drug delivery.

"One-Pot" Method Preparation of Dendritic Mesoporous Silica-Loaded Matrine Nanopesticide for Noninvasive Administration Control of Monochamus alternatus: The Vector Insect of Bursapherenchus xylophophilus.

Monochamus alternatus is an important stem-boring pest in forestry. However, the complex living environment of Monochamus alternatus creates a natural barrier to chemical control, resulting in a very limited control effect by traditional insecticidal pesticides. In this study, a stable pesticide dendritic mesoporous silica-loaded matrine nanopesticide (MAT@DMSNs) was designed by encapsulating the plant-derived pesticide matrine (MAT) in dendritic mesoporous silica nanoparticles (DMSNs). The results showed that MAT@DMSNs, sustainable nanobiopesticides with high drug loading capacity (80%) were successfully constructed. The release efficiency of DMSNs at alkaline pH was slightly higher than that at acidic pH, and the cumulative release rate of MAT was about 60% within 25 days. In addition, the study on the toxicity mechanism of MAT@DMSNs showed MAT@DMSNs were more effective than MAT and MAT (0.3% aqueous solutions) in touch and stomach toxicity, which might be closely related to their good dispersibility and permeability. Furthermore, MAT@DMSNs are also involved in water transport in trees, which can further transport the plant-derived insecticides to the target site and improve its insecticidal effect. Meanwhile, in addition, the use of essential oil bark penetrants in combination with MAT@DMSNs effectively avoids the physical damage to pines caused by traditional trunk injections and the development of new pests and diseases induced by the traditional trunk injection method, which provides a new idea for the application of biopesticides in the control of stem-boring pests in forestry.

Drug Nanocrystals: A Delivery Channel for Antiviral Therapies.

Viral infections represent a significant threat to global health due to their highly communicable and potentially lethal nature. Conventional antiviral interventions encounter challenges such as drug resistance, tolerability issues, specificity concerns, high costs, side effects, and the constant mutation of viral proteins. Consequently, the exploration of alternative approaches is imperative. Therefore, nanotechnology-embedded drugs excelled as a novel approach purporting severe life-threatening viral disease. Integrating nanomaterials and nanoparticles enables ensuring precise drug targeting, improved drug delivery, and fostered pharmacokinetic properties. Notably, nanocrystals (NCs) stand out as one of the most promising nanoformulations, offering remarkable characteristics in terms of physicochemical properties (higher drug loading, improved solubility, and drug retention), pharmacokinetics (enhanced bioavailability, dose reduction), and optical properties (light absorptivity, photoluminescence). These attributes make NCs effective in diagnosing and ameliorating viral infections. This review comprises the prevalence, pathophysiology, and resistance of viral infections along with emphasizing on failure of current antivirals in the management of the diseases. Moreover, the review also highlights the role of NCs in various viral infections in mitigating, diagnosing, and other NC-based strategies combating viral infections. In vitro, in vivo, and clinical studies evident for the effectiveness of NCs against viral pathogens are also discussed.

Interplay of Drug-Polymer Interactions and Release Performance for HPMCAS-Based Amorphous Solid Dispersions.

The interplay between drug and polymer chemistry and its impact on drug release from an amorphous solid dispersion (ASD) is a relatively underexplored area. Herein, the release rates of several drugs of diverse chemistry from hydroxypropyl methylcellulose acetate succinate (HPMCAS)-based ASDs were explored using surface area normalized dissolution. The tendency of the drug to form an insoluble complex with HPMCAS was determined through coprecipitation experiments. The role of pH and the extent of drug ionization were probed to evaluate the role of electrostatic interactions in complex formation. Relationships between the extent of complexation and the drug release rate from an ASD were observed, whereby the drugs could be divided into two groups. Drugs with a low extent of insoluble complex formation with HPMCAS tended to be neutral or anionic and showed reasonable release at pH 6.8 even at higher drug loadings. Cationic drugs formed insoluble complexes with HPMCAS and showed poor release when formulated as an ASD. Thus, and somewhat counterintuitively, a weakly basic drug showed a reduced release rate from an ASD at a bulk solution pH where it was ionized, relative to when unionized. The opposite trend was observed in the absence of polymer for the neat amorphous drug. In conclusion, electrostatic interactions between HPMCAS and lipophilic cationic drugs led to insoluble complex formation, which in turn resulted in ASDs with poor release performance.

A self-assembly active nanomodulator based on berberine for photothermal immunotherapy of breast cancer via dual regulation of immune suppression

Breast cancer (BC) remains a significant global health concern, especially affecting women, necessitating the development of effective treatment strategies. Photothermal immunotherapy has holds promise for addressing BC by eradicating tumors, preventing metastasis, and reducing recurrence rates. However, the dynamic amplification of indoleamine 2,3-dioxygenase 1 (IDO-1) and programmed cell death-ligand 1 (PD-L1) triggered by photothermal therapy (PTT) poses presents a significant barrier to immune cell infiltration, thus promoting immune evasion. To enhance overall efficiency, a hyaluronic acid (HA)-coated berberine (BBR)-indocyanine green self-assembly active nano modulator (HBI NDs) was successfully developed. This nano modulator aims to reverse immune resistance and further contribute to the synergistic anti-tumor effects. The prepared HBI NDs demonstrated a uniform spherical morphology, high drug loading, and favorable optical properties. The results based on in vitro cell experiments and tumor animal models confirmed that HBI NDs selectively accumulated in tumor tissues, downregulated PD-L1 and IDO-1 protein expression, and induced elevated cell apoptosis. Consequently, these effects result in efficient immune infiltration and positive anti-tumor outcomes. In conclusion, the HBI NDs nanodrug exhibits considerable potential as a novel agent for enhancing anticancer efficacy and promoting immune infiltration.

Preparation of PLGA Microspheres Using the Non-Toxic Glycofurol as Polymer Solvent by a Modified Phase Inversion Methodology.

Poly(D,L-lactide-co-glycolide is a biodegradable copolymer that can release pharmaceuticals. These pharmaceuticals can provide local therapy and also avert the clinical issues that occur when a drug must be given continuously and/or automatically. However, the drawbacks of using poly(D,L-lactide-co-glycolide include the kinetics and duration of time of poly(D,L-lactide-co-glycolide drug release, the denaturing of the drug loaded drug, and the potential clinical side effects. These drawbacks are mainly caused by the volatile organic solvents needed to prepare poly(D,L-lactide-co-glycolide spheres. Using the non-toxic solvent glycofurol solvent instead of volatile organic solvents to construct poly(D,L-lactide-co-glycolide microspheres may deter the issues of using volatile organic solvents. Up to now, preparation of such glycofurol spheres has previously met with limited success. We constructed dexamethasone laden poly(D,L-lactide-co-glycolide microspheres utilizing glycofurol as the solvent within a modified phase inversion methodology. These prepared microspheres have a higher drug load and a lower rate of water diffusion. This prolongs drug release compared to dichloromethane constructed spheres. The glycofurol-generated spheres are also not toxic to target cells as is the case for dichloromethane-constructed spheres. Further, glycofurol-constructed spheres do not denature the dexamethasone molecule and have kinetics of drug release that are more clinically advantageous, including a lower drug burst and a prolonged drug release.

Application of microwave vacuum drying with process management in extract drying of personalized traditional Chinese medicine preparations

Extracts are important intermediates in the production of traditional Chinese medicines preparations. The drying effect of extracts will directly affect the subsequent production process and the quality of the preparation. To meet the requirements of high drug loading, short time consumption, and simple production process of personalized traditional Chinese medicine preparations, this study explored the application of multi-program microwave vacuum drying process in the extract drying of personalized traditional Chinese medicine preparations. The influencing factors of microwave vacuum drying process were investigated for 5 excipients and 40 prescriptions. Taking the feasibility of drying, drying rate, drying time, and dried extract status as indicators, this study investigated the feeding requirements of microwave vacuum drying. With the dried extract status as the evaluation indicator, the three drying programs(A, B, and C) were compared to obtain the optimal drying condition. The experimental results showed that the optimal feeding conditions for microwave vacuum drying were material layer thickness of 2 cm and C program(a total of 7 drying processes), which solved the problem of easy scorching in microwave drying with process management. Furthermore, the preset moisture content of the dried extract in microwave drying should be 4%-5%, so that the dried extract of traditional Chinese medicine preparation had uniform quality, complete drying, and no scorching. This study lays a foundation for the application of microwave drying in the production of traditional Chinese medicine preparations, promoting the high-quality development of personalized traditional Chinese medicine preparations.

Advances in superparamagnetic iron oxide nanoparticles modified with branched polyethyleneimine for multimodal imaging

Multimodal imaging are approaches which combines multiple imaging techniques to obtain multi-aspect information of a target through different imaging modalities, thereby greatly improve the accuracy and comprehensiveness of imaging. Superparamagnetic iron oxide nanoparticles (SPIONs) modified with branched polyethyleneimine have revealed good biocompatibility and stability, high drug loading capacity and nucleic acid transfection efficiency. SPIONs have been developed as functionalized platforms which can be further modified to enhance their functionalities. Those further modifications facilitate the application of SPIONs in multimodal imaging. In this review, we discuss the methods, advantages, applications, and prospects of BPEI-modified SPIONs in multimodal imaging.

Tunable self-assembly of lipid-based block polymeric micelles with temperature-sensitive poly(vinylcaprolactam) shell for effective anticancer drug delivery

Lipids, as naturally occurring biomolecules have emerged as promising carriers for delivering various therapeutic agents. However, only a few attempts have been made in terms of their applications as amphiphilic block copolymers for anticancer drug delivery. In this work, a biocompatible micellar drug delivery system with fatty acid-based polymer core and temperature-sensitive shell was developed. A series of amphiphilic block copolymers poly(vinyl stearate)/poly(vinyl laurate)-b-poly(N-vinylcaprolactam) (PVS/PVL-b-PNVCL) were synthesized via microwave-assisted reversible addition-fragmentation chain transfer polymerization in a controlled fashion. By varying the fatty acid type and hydrophilic/hydrophobic block lengths, the self-assembly behaviour of the block copolymer micelles proved to be highly tunable in terms of their morphology and particle size. Nile Red and hydrophobic anticancer drug doxorubicin (DOX) were effectively incorporated into the micelles, demonstrating high drug loading capacity, good serum stability, and temperature-dependent drug release characteristics of the polymeric micelles. In vitro studies using cell models revealed that blank PVS -b-PNVCL micelles are biocompatible with different cell lines, while DOX-loaded micelles were internalized into and accumulated in the cells, showing a high cytotoxic effect against HeLa cells. These findings suggest an opportunity for the development of safe and efficient lipid-based micellar system for smart drug delivery and cancer treatments.

Formulation and Evaluation of Lipid Based Nanoparticles of Etravirine

Engineered nanoparticles have the potential to revolutionize the diagnosis and treatment of many diseases like HIV/AIDS. Etravirine is one of the key components of highly active antiretroviral therapy used for the treatment of HIV-1 infections. The aim of the present study was to formulate and evaluate nanostructured lipid carriers of etravirine, intended for targeted delivery to macrophages, using solvent emulsification - evaporation technique. Estimates of drug solubility were employed for selection of solid lipids, liquid lipids and stabilizers for the preparation of NLCs. Design of experiments was used to optimize the formulation with respect to drug-lipid ratio and concentration of stabilizer in the external phase using 32 full factorial design. Particle size of the carriers and drug release characteristics were the responses which were set to suitable levels for optimization. The optimized formulation was prepared and characterized for size, poly dispersity index, zeta potential, entrapment efficiency and appearance. The nanostructured lipid carriers of etravirine were prepared using stearylamine and glyceryl monostearate as solid lipids, Capryol 90 as liquid lipid and polyvinyl pyrrolidone as stabilizer. All experimental batches showed high drug loading efficiencies nearing 99%, indicating that etravirine remained closely associated with the lipids. The nanostructured lipid carriers displayed a zeta potential of -10.1 mv and a particle size of 261.6 nm with a polydispersity index of 0.374. In vitro release of etravirine from the optimized formulation at 2 h was 9% indicative of a low burst; and 56% of the entrapped drug was released after 24 h, suggesting prolonged release characteristics. Thus, etravirine loaded lipidic nanoparticles with potential for targeting cellular reservoirs of the AIDS virus such as macrophages were successfully developed.&#x0D; Keywords: Etravirine, Nanostructured lipid carriers, full factorial design

Single-, Dual-, and Multi-Stimuli-Responsive Nanogels for Biomedical Applications.

In recent years, stimuli-responsive nanogels that can undergo suitable transitions under endogenous (e.g., pH, enzymes and reduction) or exogenous stimuli (e.g., temperature, light, and magnetic fields) for on-demand drug delivery, have received significant interest in biomedical fields, including drug delivery, tissue engineering, wound healing, and gene therapy due to their unique environment-sensitive properties. Furthermore, these nanogels have become very popular due to some of their special properties such as good hydrophilicity, high drug loading efficiency, flexibility, and excellent biocompatibility and biodegradability. In this article, the authors discuss current developments in the synthesis, properties, and biomedical applications of stimulus-responsive nanogels. In addition, the opportunities and challenges of nanogels for biomedical applications are also briefly predicted.

Fabrication of hyaluronic acid with graphene quantum dot as a dual drug delivery system for cancer therapy

With recent advancements in nanomedicine, there has been growing interest in developing drug delivery systems with multifunctional capabilities. In this study, we developed a novel dual drug delivery system by combining two drug carriers via positive and negative electrostatic interactions. First, we modified polyethyleneimine (PEI) with graphene quantum dots (GQDs) to create a positively charged particle (GPI) with high drug loading efficiency and good dispersibility. Second, we embedded the pyrenebutyric acid structure in hyaluronic acid (HA) through EDC/NHS cross-linking and used TAK-632 as the hydrophobic drug to create negatively charged particles (HANPs) with hydrogel-like properties and the CD44 receptor. After the two components were constructed, the increase in the particle charge and simultaneous delivery of both drugs synergistically enhanced the therapeutic effect of this strategy. Qualitative tests confirmed the successful synthesis of the drug carrier, while the potential of this system as a cancer treatment strategy was evaluated in HCT116 cancer cells (through MTT cell viability assays) and in vivo mice xenograft experiments. Our results demonstrated that the dual drug delivery system, HANPs(TAK)/GPI(DOX), had a significant inhibitory effect on the growth of cancer cells both in vitro and in vivo, suggesting that this system is a promising candidate for a new type of treatment.

Chia (Salvia hispanica L.) seed mucilage (a heteropolysaccharide) based antimicrobial hydrogel scaffold for wound healing: In vitro-in-vivo characterization

Wound healing is an intricate process necessitating the utilization of innovative bioactive materials to enhance and expedite recovery. Polysaccharide-based hydrogels for wound dressing have garnered significant attention due to their commendable biocompatibility, biodegradability, and non-toxic properties. Consequently, this study will design zinc oxide nanoparticles (ZnONP) and allantoin (AT) incorporated chia seed mucilage (CSM) based antimicrobial hydrogel scaffold via solvent casting method to accelerate the wound healing process. The confirmation of an ideal CSM/20 %ZnONP/AT hydrogel scaffold is achieved through spectral analysis and assessment of mechanical properties. The scaffold exhibits notable characteristics, including 36.99 % of porosity, 20.34 degrees of swelling, 63.38 % of water retention capacity, and 11.16 % of moisture content. Importantly, the hydrogel demonstrates no cytotoxicity towards normal cell lines (log p > 0.05), high drug loading efficiency (98.75 %), and 34.16 % release of AT within 8 h, following a first-order release (R2 = 0.9892). Additionally, it manifests good antibacterial and antifungal activity attributed to the presence of ZnONP within the scaffold. In vivo studies conducted using a Wistar rat model displayed a substantial reduction in wound size (90.70 %) within 14 days compared to the control group. Histopathological analysis indicates the dynamic progression of the healing process facilitated by the application of AT in conjunction with CSM and ZnONP. The enhanced performance of the CSM/20 %ZnONP/AT hydrogel scaffold is attributed to the distinctive characteristics of CSM, ZnONP, and AT. This study anticipates that CSM-based hydrogel scaffolds will pave the way for novel and promising applications in the field of wound healing.

Modeling and characterization of lenalidomide-loaded tripolyphosphate-crosslinked chitosan nanoparticles for anticancer drug delivery

Tripolyphosphate-crosslinked chitosan (TPPCS) nanoparticles were employed in the encapsulation of lenalidomide (LND) using a straightforward ionic cross-linking approach. The primary objectives of this technique were to enhance the bioavailability of LND and mitigate inadequate or overloading of hydrophobic and sparingly soluble drug towards cancer cells. In this context, a quantum chemical model was employed to elucidate the characteristics of TPPCS nanoparticles, aiming to assess the efficiency of these nanocarriers for the anticancer drug LND. Fifteen configurations of TPPCS and LND (TPPCS /LND1-15) were optimized using B3LYP density functional level of theory and PCM model (H2O). AIM analysis revealed that the high drug loading capacity of TPPCS can be attributed to hydrogen bonds, as supported by the average binding energy (168 kJ mol−1). The encouraging theoretical results prompted us to fabricate this drug delivery system and characterize it using advanced analytical techniques. The encapsulation efficiency of LND within the TPPCS was remarkably high, reaching approximately 87 %. Cytotoxicity studies showed that TPPCS/LND nanoparticles are more effective than the LND drug. To sum up, TPPCS/LND nanoparticles improved bioavailability of poorly soluble LND through cancerous cell membrane. In light of this accomplishment, the novel drug delivery route enhances efficiency, allowing for lower therapy doses.