Design Of Drug Delivery Systems Research Articles

Challenges and Opportunities Associated With Drug Delivery for the Treatment of Solid Tumors.

In this review, we discuss the effectiveness of drug delivery system based on metal nanoparticles, and also, describe the problems associated with their delivery to tumor cells. Throughout recent years, more reports have appeared in the literature that demonstrate promising results for the treatment of various types of cancer using metal-based nanoparticles. Due to their unique physical and chemical properties, metal nanoparticles are effectively being used for the delivery of drug to the tumor cells, for cancer diagnosis and treatment. They can also be synthesized allowing the control of size and shape. However, the effectiveness of the metal nanoparticles for cancer treatment largely depends on their stability, biocompatibility, and ability to selectively affect tumor cells after their systemic or local administration. Another major problem associated with metal nanoparticles is their ability to overcome tumor tissue barriers such as atypical blood vessel structure, dense and rigid extracellular matrix, and high pressure of tumor interstitial fluid. The review also describes the design of tumor drug delivery systems that are based on metal nanoparticles. The mechanism of action of metal nanoparticles on cancer cells is also discussed. Considering the therapeutic safety and toxicity of metal nanoparticles, the prospects for their use for future clinical applications are being currently reviewed.

Physiologically Based Pharmacokinetic Modeling of Extracellular Vesicles.

Extracellular vesicles (EVs) are lipid membrane bound-cell-derived structures that are a key player in intercellular communication and facilitate numerous cellular functions such as tumor growth, metastasis, immunosuppression, and angiogenesis. They can be used as a drug delivery platform because they can protect drugs from degradation and target specific cells or tissues. With the advancement in the technologies and methods in EV research, EV-therapeutics are one of the fast-growing domains in the human health sector. Therapeutic translation of EVs in clinics requires assessing the quality, safety, and efficacy of the EVs, in which pharmacokinetics is very crucial. We report here the application of physiologically based pharmacokinetic (PBPK) modeling as a principal tool for the prediction of absorption, distribution, metabolism, and excretion of EVs. To create a PBPK model of EVs, researchers would need to gather data on the size, shape, and composition of the EVs, as well as the physiological processes that affect their behavior in the body. The PBPK model would then be used to predict the pharmacokinetics of drugs delivered via EVs, such as the rate at which the drug is absorbed and distributed throughout the body, the rate at which it is metabolized and eliminated, and the maximum concentration of the drug in the body. This information can be used to optimize the design of EV-based drug delivery systems, including the size and composition of the EVs, the route of administration, and the dose of the drug. There has not been any dedicated review article that describes the PBPK modeling of EV. This review provides an overview of the absorption, distribution, metabolism, and excretion (ADME) phenomena of EVs. In addition, we will briefly describe the different computer-based modeling approaches that may help in the future of EV-based therapeutic research.

Design and synthesis of multivalent drug delivery system with CA IX inhibitors as ligands

A multivalent ligand delivery system holds tremendous potential in the field of tumor-targeted drug delivery. It addresses the challenges posed by the low affinity between small molecule ligand receptors and the rapid metabolism of small molecule drug conjugates (SMDCs) in vivo. Notably, existing multivalent ligand systems have demonstrated significant anti-tumor activity in various tumor models. In this study, we have developed a novel multivalent ligand delivery system for SN38, utilizing acetazolamide, a carbonic anhydrase IX (CA IX) inhibitor, as the target ligand. Our multivalent ligand delivery systems exhibited superior metabolic stability and enhanced targeting specificity compared to SMDC molecules. Furthermore, they demonstrated improved anti-proliferation activity, addressing the existing challenges associated with the low receptor affinity and rapid metabolism of SMDCs.

Advances in Structure Pharmaceutics from Discovery to Evaluation and Design.

Drug delivery systems (DDSs) play an important role in delivering active pharmaceutical ingredients (APIs) to targeted sites with a predesigned release pattern. The chemical and biological properties of APIs and excipients have been extensively studied for their contribution to DDS quality and effectiveness; however, the structural characteristics of DDSs have not been adequately explored. Structure pharmaceutics involves the study of the structure of DDSs, especially the three-dimensional (3D) structures, and its interaction with the physiological and pathological structure of organisms, possibly influencing their release kinetics and targeting abilities. A systematic overview of the structures of a variety of dosage forms, such as tablets, granules, pellets, microspheres, powders, and nanoparticles, is presented. Moreover, the influence of structures on the release and targeting capability of DDSs has also been discussed, especially the in vitro and in vivo release correlation and the structure-based organ- and tumor-targeting capabilities of particles with different structures. Additionally, an in-depth discussion is provided regarding the application of structural strategies in the DDSs design and evaluation. Furthermore, some of the most frequently used characterization techniques in structure pharmaceutics are briefly described along with their potential future applications.

Preparation and Characterization of Hydrogel Films and Nanoparticles Based on Low-Esterified Pectin for Anticancer Applications.

Prospective adjuvant anticancer therapy development includes the establishing of drug delivery systems based on biocompatible and biodegradable carriers. We have designed films and nanoparticles (NPs) based on low-esterified pectin hydrogel using the ionic gelation method. We investigated morphology, nanomechanical properties, biocompatibility and anticancer activity. Hydrogel films are characterized by tunable viscoelastic properties and surface nanoarchitectonics through pectin concentration and esterification degree (DE), expressed in variable pore frequency and diameter. An in vitro study showed a significant reduction in metabolic activity and the proliferation of the U87MG human glioblastoma cell line, probably affected via the adhesion mechanism. Glioma cells formed neurosphere-like conglomerates with a small number of neurites when cultured on fully de-esterified pectin films and they did not produce neurites on the films prepared on 50% esterified pectin. Pectin NPs were examined in terms of size distribution and nanomechanical properties. The NPs' shapes were proved spherical with a mean diameter varying in the range of 90-115 nm, and a negative zeta potential from -8.30 to -7.86 mV, which indicated their stability. The NPs did not demonstrate toxic effect on cells or metabolism inhibition, indicating good biocompatibility. Nanostructured biomaterials prepared on low-esterified pectins could be of interest for biomedical applications in adjuvant anticancer therapy and for designing drug delivery systems.

Multifunctional modified carbon nanotubes as potential anti-tumor drug delivery

The main issues associated with antitumor chemotherapy are the nonspecific and systemic toxicity induced by different types of drugs. In the other hand, the ability of tumor cells to hinder the internalization and metabolism of chemotherapy drugs affects the efficacy of antitumoral therapies. In this context, our work hypothesizes that the development of novel drug delivery systems targeting alternative sites could serve as a strategy to deliver specific and effective antitumoral activity. This study focuses on the synthesis, chemical characterization and biological evaluation of a novel rational dual drug delivery system (DDS) based on non-covalent functionalization. The DDS employed multi-walled carbon nanotubes (MWCNT) as vectors, which are conjugated with folic acid (FA) to facilitate targeted delivery to tumor sites and enhance bioavailability. Additionally, digoxin (DGX) was incorporated as a cytotoxic agent. Several characterization techniques such as X-ray diffraction, thermogravimetric analysis, Raman and infrared spectroscopy were employed to identify the characteristics attributed to the carbon-based nanomaterials and the organic molecules attached on the MWCNT. Transmission electron microscopy analysis revealed the presence of adsorbed aggregates on the surface of the nanotubes. In silico molecular docking studies identified energetically favorable interaction modes between FA and DGX on the MWCNT walls. A drug release assay was performed to elucidate the mechanism of action of the dual drug delivery system. Subsequently, MWCNT, digoxin and the newly developed hybrids were incubated with HeLa cells (cervical cancer) to assess cell viability using the MTT reduction assay. Our findings demonstrated the absence of acute cytotoxicity associated with MWCNT, whereas the DDS exhibited significant cytotoxicity, reducing tumor cell viability at safe concentrations of digoxin. These results shed light on the design and advantages of novel rational drug delivery systems that explore the potential of MWCNT, repurposed antitumor drugs, and membrane tumor biomarkers. Importantly, the synthesis of a dual drug delivery system comprising digoxin and folic acid represents a pioneering achievement in the field to date.

Predicting particle deposition using a simplified 8-path in silico human lung prototype

Understanding particle deposition in the human lung is crucial for the assessment of environmental pollutants and the design of new drug delivery systems. Traditionally, research has been carried out by experimental analysis, but this generally requires expensive equipment and exposure of volunteers to radiation, resulting in limited data. To overcome these drawbacks, there is an emphasis on the development of numerical models capable of accurate predictive analysis. The most advanced of these computer simulations are based on three-dimensional computational fluid dynamics. Solving the flow equations in a complete, fully resolved lung airway model is currently not feasible due to the computational resources required. In the present work, a simplified lung model is presented and validated for accurate prediction of particle deposition. Simulations are performed for an 8-path approximation to a full lung airway model. A novel boundary condition method is used to ensure accurate results in truncated flow branches. Simulations are performed at a steady inhalation flow rate of 18 l min−1, corresponding to a low activity breathing rate, while the effects of particle size and density are investigated. Comparison of the simulation results with available experimental data shows that reasonably accurate results can be obtained at a small fraction of the cost of a full airway model. The simulations clearly evaluate the effect of both particle size and particle density. Most importantly, the results show an improvement over a previously documented single-path model, both in terms of accuracy and the ability to obtain regional deposition rates. The present model represents an improvement over previously used simplified models, including single-path models. The multi-path reduced airway approach described can be used by researchers for general and patient-specific analyses of particle deposition and for the design of effective drug delivery systems.

Individually Tailored Modular "Egg" Hydrogels Capable of Spatiotemporally Controlled Drug Release for Spinal Cord Injury Repair.

Controllable drug delivery systems (DDS) can overcome the disadvantages of conventional drug administration processes, such as high dosages or repeated administration. Herein, we deploy a smart DDS collagen hydrogel for spinal cord injury (SCI) repair based on modular designing of "egg" nanoparticles (NPs) that ingeniously accomplish controlled drug release via inducing a signaling cascade in response to external and internal stimuli. The "egg" NPs consist of a three-layered structure: tannic acid/Fe3+ /tetradecanol "eggshell," zeolitic imidazolate framework-8 (ZIF-8) "egg white," and paclitaxel "yolk". Then NPs served as a crosslinking epicenter, blending with collagen solutions to generate functional hydrogels. Remarkably, the "eggshell" efficiently converts near-infrared (NIR) irradiation into heat. Subsequently, tetradecanol can be triggered to disintegrate via heat, exposing the structure of ZIF-8. The Zn-imidazolium ion coordination bond of the "egg white" was susceptible to cleaving at the acidic SCI site, decomposing the skeleton to release paclitaxel on demand. As expected, the paclitaxel release rate upon NIR irradiation increased up to 3-folds on the seventh day, which matches endogenous neural stem/progenitor cell migration process. Taken together, the collagen hydrogels facilitated the neurogenesis and motor function recovery, demonstrating a revolutionary strategy for spatiotemporally controlled drug release and providing guidelines for the design of DDS. This article is protected by copyright. All rights reserved.

Intraoral Drug Delivery: Highly Thiolated κ-Carrageenan as Mucoadhesive Excipient.

This study aims to design a novel thiolated κ-carrageenan (κ-CA-SH) and evaluate its potential as an excipient for the design of mucoadhesive drug delivery systems. Native κ-carrageenan (κ-CA) was thiolated with phosphorous pentasulfide in sulfolane and characterized via 1H NMR, FTIR, as well as Ellman's test. Cytotoxicity was assessed via resazurin assay. In vitro release of the model drug, benzydamine hydrochloride, was determined. Tensile and mucosal residence time studies were performed on buccal and small intestinal mucosa. Mucoadhesive features were investigated via rheological studies with freshly isolated porcine mucus. Thiolated κ-CA (κ-CA-SH) with 1213.88 ± 52 µmol/g thiol groups showed no cytotoxicity at a concentration of 1% (m/v) and low cytotoxicity up to 2% (m/v). Benzydamine hydrochloride showed slow release in solution for both polymers. Tensile studies on buccal and intestinal mucosa showed an up to 2.7-fold and 7.7-fold enhancement in the maximum detachment force (MDF) and total work of adhesion (TWA) of κ-CA-SH vs. κ-CA, respectively. The κ-CA-SH exhibited an up to 4.4-fold improved dynamic viscosity with mucus and significantly prolonged residence time on mucosa compared to native κ-CA. Since highly thiolated κ-CA shows a slow release of positively charged active pharmaceutical ingredients and enhanced mucoadhesive properties, it might be a promising excipient for local drug delivery in the oral cavity.

Natural polysaccharide-based smart CXCR4-targeted nano-system for magnified liver fibrosis therapy

Activated hepatic stellate cells (aHSCs), the main source of extracellular matrix deposition, are key targets in liver fibrosis. However, no effective drug specific to aHSCs has been clinically applied due to poor drug delivery efficiency. Herein, we designed a CXC chemokine receptor 4 (CXCR4)-targeted reactive oxygen species (ROS)-responsive platform AMD-Dex-ROS-responsive-sorafenib (ARS) based on natural polysaccharide and thioctic acid frame, which can deliver anti-fibrosis drug represented by sorafenib specifically to aHSCs on account of CXCR4 over-expression on aHSCs, and smartly disassemble via ROS-responsive thioketal rupture relying on high intracellular ROS in HSCs, realized on-demand drug release and effective liver fibrosis reversion. Notably, in this platform, the CXCR4 antagonist AMD3100 not only enhanced aHSCs targeting efficiency of sorafenib but also effectively magnified the aHSCs elimination of sorafenib by blocking stroma cell derived factor-1 (SDF-1)/CXCR4-induced aHSCs protection, resulting in synergistic anti-fibrosis effect. The platform provided a new approach for drug delivery system design and liver fibrosis treatment.

Influence of heterogeneity or shape on the locomotion of a caged squirmer

The development of novel drug delivery systems, which are revolutionizing modern medicine, is benefiting from studies on microorganisms’ swimming. In this paper we consider a model microorganism (a squirmer) enclosed in a viscous droplet to investigate the effects of medium heterogeneity or geometry on the propulsion speed of the caged squirmer. We first consider the squirmer and droplet to be spherical (no shape effects) and derive exact solutions for the equations governing the problem. For a squirmer with purely tangential surface velocity, the squirmer is always able to move inside the droplet (even when the latter ceases to move as a result of large fluid resistance of the heterogeneous medium). Adding radial modes to the surface velocity, we establish a new condition for the existence of a co-swimming speed (where squirmer and droplet move at the same speed). Next, to probe the effects of geometry on propulsion, we consider the squirmer and droplet to be in Newtonian fluids. For a squirmer with purely tangential surface velocity, numerical simulations reveal a strong dependence of the squirmer's speed on shapes, the size of the droplet and the viscosity contrast. We found that the squirmer speed is largest when the droplet size and squirmer's eccentricity are small, and the viscosity contrast is large. For co-swimming, our results reveal a complex, non-trivial interplay between the various factors that combine to yield the squirmer's propulsion speed. Taken together, our study provides several considerations for the efficient design of future drug delivery systems.

Mathematical modelling of microneedle-mediated transdermal delivery of drug nanocarriers into skin tissue and circulatory system

Microneedle-mediated transdermal delivery using nanocarriers can successfully overcome the barrier of the stratum corneum and protect drugs from elimination in skin tissues. However, the effectiveness of drug delivery to different layers of skin tissues and the circulatory system varies considerably, subject to the properties of the drug delivery system and delivery regime. How to maximise delivery outcomes remains unclear. In this study, mathematical modelling is employed to investigate this transdermal delivery under various conditions, using the skin model that is reconstructed based on the realistic skin anatomical structure. Treatment efficacy is evaluated in terms of drug exposure over time. The modelling results demonstrate the complex dependence of drug accumulation and distribution on the nanocarrier properties, microneedle properties and environment in different skin layers and blood. Specifically, delivery outcomes in the entire skin and blood can be improved by increasing the loading dose and reducing microneedle spacing. However, several parameters need to be optimised with respect to the specific location of the target site in the tissue for better treatment; these include the drug release rate, nanocarrier diffusivity in microneedle and skin tissue, nanocarrier transvascular permeability, nanocarrier partition coefficient between tissue and microneedle, microneedle length, wind speed and relative humidity. The delivery is less sensitive to the diffusivity and physical degradation rate of free drugs in microneedle, and their partition coefficient between tissue and microneedle. Results obtained from this study can be used to improve the design of the microneedle-nanocarrier combined drug delivery system and delivery regime.

Application of Box-Behnken Design in microparticle production of p-Toluenesulfonamide through the rapid expansion of supercritical solutions process

p-Toluenesulfonamide (PTS) is a developing small molecular anticancer agent with good lipophilic ability. Microparticle production of PTS is an approach to enhance the dissolution profile and explore the potential for novel drug delivery system design. This study employed the rapid expansion of supercritical solutions (RESS) process to produce microparticles of PTS using supercritical carbon dioxide as the solvent. To meet the concept of quality by design in the pharmaceutical industry, the effects of process parameters in RESS operation were investigated and optimized by a design of experiments approach, the Box-Behnken Design (BBD). The design space for microparticle production of PTS was shown, and the analysis of variance (ANOVA) confirmed the significance of process parameters. According to the BBD study, at the optimal operating condition, PTS microparticles were successfully generated from the unprocessed mean size of 240.3 μm to 1.3 μm. The solid-state property of the unprocessed and micronized PTS powders was compared and confirmed consistent through the PXRD, DSC, and FTIR analysis. Finally, the dissolution profiles of PTS before and after the RESS process were determined, and the dissolution rate of RESS-produced PTS microparticles was enhanced 1500 times compared with the unprocessed PTS.

Dextran-based micelles for combinational chemo-photodynamic therapy of tumors via in vivo chemiluminescence

Natural polysaccharides, represented by dextran, chitosan, and hyaluronic acid, are widely approved for use as pharmaceutical excipients and are important carrier materials for the design of advanced drug delivery systems, particularly in the field of anticancer drug delivery. The combination of stimuli-activable prodrug based chemotherapy and photodynamic therapy (PDT) has attracted increasing attention. Recent studies have verified the effectiveness of this strategy in the treatment of multiple aggressive cancers. However, in such combination, the stimuli-responsive chemotherapy and PDT have their own problems that need to be overcome. The uneven distribution of endogenous stimuli within tumor tissues makes it difficult for prodrug to be completely activated. And the inadequate tissue penetration depth of external light results in low efficiency of PDT. Aiming at these two bottlenecks, we designed a biocompatible dextran based - multi-component nanomedicine (PCL-NPs) that integrate a chemiluminescence agent luminol, a photosensitizer chlorine e6 (Ce6), and a reactive oxygen species (ROS)-activable thioketal-based paclitaxel (PTX) prodrug. The presence of overexpressed hydrogen peroxide (H2O2) inside tumor oxidizes the luminol moiety to generate in-situ light for PDT through chemiluminescence resonance energy transfer (CRET). The singlet oxygen (1O2) produced in this process not only directly kills tumor cells but also amplifies oxidative stress to accelerate the activation of PTX prodrug. We propose that the PCL-NPs have great therapeutic potential by simultaneously enhancing chemotherapy and PDT in a combination therapy.

Impact of Molecular Building Blocks on Dynamic Nature of Novel Biomimetic Drug Delivery Systems as Ufasomes and Ufosomes: Modification in Structure and Surface Charge

Abstract: This review is focused on the self-assembly of different molecular building blocks at var-ious levels of complexity. In this perspective, we present the basic concept and recent research on the self-assembly of fatty acids and their derivatives, surfactants, and cholesterol. In addition, we discuss the conditions for designing and stabilizing novel vesicular drug delivery systems and how the flux changes due to the molecular structure of building blocks. Furthermore, the article provides a brief discussion on fatty acid and oleate self-assembly, which is becoming an emerging nanotech-nology because of its ability to alter the dynamic nature of the skin. These structures have been shown to enhance the skin permeability of drugs and other active compounds, making them poten-tial candidates for transdermal drug delivery. In conclusion, the self-assembly of various molecular building blocks at different levels of complexity has significant implications in the fields of drug de-livery, cosmetics, and nanotechnology. The ability to control and manipulate the self-assembly pro-cess offers a wide range of possibilities for the design of novel and efficient drug delivery systems.

Amelioration of Cancer Employing Chitosan, Its Derivatives, and Chitosan-Based Nanoparticles: Recent Updates.

The limitations associated with the conventional treatment of cancer have necessitated the design and development of novel drug delivery systems based mainly on nanotechnology. These novel drug delivery systems include various kinds of nanoparticles, such as polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, hydrogels, and polymeric micelles. Among the various kinds of novel drug delivery systems, chitosan-based nanoparticles have attracted the attention of researchers to treat cancer. Chitosan is a polycationic polymer generated from chitin with various characteristics such as biocompatibility, biodegradability, non-toxicity, and mucoadhesiveness, making it an ideal polymer to fabricate drug delivery systems. However, chitosan is poorly soluble in water and soluble in acidic aqueous solutions. Furthermore, owing to the presence of reactive amino groups, chitosan can be chemically modified to improve its physiochemical properties. Chitosan and its modified derivatives can be employed to fabricate nanoparticles, which are used most frequently in the pharmaceutical sector due to their possession of various characteristics such as nanosize, appropriate pharmacokinetic and pharmacodynamic properties, non-immunogenicity, improved stability, and improved drug loading capacity. Furthermore, it is capable of delivering nucleic acids, chemotherapeutic medicines, and bioactives using modified chitosan. Chitosan and its modified derivative-based nanoparticles can be targeted to specific cancer sites via active and passive mechanisms. Based on chitosan drug delivery systems, many anticancer drugs now have better effectiveness, potency, cytotoxicity, or biocompatibility. The characteristics of chitosan and its chemically tailored derivatives, as well as their use in cancer therapy, will be examined in this review.

Enhanced anticancer effect of Artemisia turcomanica extract in niosomal formulation on breast cancer cells: In-vitro study

Artemisia turcomanica is a medicinal plant that has been used to treat hepatitis, fever, malaria, cancer, tumors and asthma, and is considered inexpensive. In this work, we report the synthesis of niosomes loaded with Artemisia turcomanica extract and its anti-cancer properties against MCF-7 cells, as model breast cancer cells. The formulation with the highest surfactant concentration had a maximum entrapment efficiency of approximately 71.21%. Moreover, at physiological pH (7.4), the niosomal formulations exhibited a slow-release profile within three days, while at lower pH (5.4), the release rate was more significant. While the designed drug delivery system showed high biocompatibility against non-tumorigenic breast cells (MCF-10A), it showed high cytotoxicity against breast cancer cells (MCF-7 cell line). The anti-cancer effect of the Artemisia turcomanica-loaded niosomal formulation was significantly higher than free Artemisia turcomanica and pristine niosomes. The enhanced anti-cancer effect was further confirmed by regulation of different gene expression levels in MCF-7 cells and cell cycle analysis. The results of this study show the great potential of plant extract-loaded niosomes, in particular Artemisia turcomanica-loaded niosomes, as effective drug delivery systems for cancer treatment, which could impact on the future of traditional medicine cum modern medicine.

An enzyme-instructed self-assembly system induces tumor acidosis via sequential-dual effect for cancer selective therapy.

The acidosis anti-tumor therapy, based on the altered energy metabolism pathway of tumor cells, has been proposed as an attractive method for cancer selective treatment. However, the strategy of inducing tumor acidosis by using a single drug to simultaneously inhibit both lactate efflux and consumption has not been reported yet. Herein, an in situ enzyme-instructed self-assembly (EISA) system was rationally fabricated to induce tumor acidosis apoptosis for cancer selective therapy. Depending on the sequential effect of the in situ EISA system, the targeted drug was successively distributed on the membrane and intracellular, inhibiting MCT4 mediated lactate efflux and mitochondrial tricarboxylic acid (TCA) cycle mediated lactate consumption, respectively. Through the dual obstruction of lactate metabolism to trigger tumor acidosis, the in situ EISA nanomedicine showed selective growth and migration inhibition against cancer cells. In addition, the nanomedicine also displayed a radio-sensitization effect in vitro due to causing the mitochondrial dysfunction, and exhibited a prominent synergistic chemo-radiotherapy anti-tumor performance in vivo. Accordingly, this work demonstrated that the in situ EISA system could endow the LND with sequential-dual effects to induce tumor acidosis, which may provide an enlightening strategy for anticancer drug delivery and cancer selective therapy. STATEMENT OF SIGNIFICANCE: With the help of the sequential effect of in situ EISA , the serial attack of LND against different targets was effectively realized to induce tumor acidosis and combined chemo-radiotherapy, implying the importance of the relationship between structure and function, which could offer a distinctive inspiration for future drug delivery system design and anti-tumor application.

Cargo-Dependent Targeted Cellular Uptake Using Quaternized Starch as a Carrier

The tailored design of drug delivery systems for specific therapeutic agents is a prevailing approach in the field. In this paper, we present a study that highlights the potential of our modified starch, Q-starch, as a universal and adaptable drug delivery carrier for diverse therapeutic agents. We investigate the ability of Q-starch/cargo complexes to target different organelles within the cellular landscape, based on the specific activation sites of therapeutic agents. Plasmid DNA (pDNA), small interfering RNA (siRNA), and phosphatidylinositol (3,4,5)-trisphosphate (PIP3) were chosen as representative therapeutic molecules, acting in the nucleus, cytoplasm, and membrane, respectively. By carrying out comprehensive characterizations, employing dynamic light scattering (DLS), determining the zeta potential, and using cryo-transmitting electron microscopy (cryo-TEM), we reveal the formation of nano-sized, positively charged, and spherical Q-starch complexes. Our results demonstrate that these complexes exhibit efficient cellular uptake, targeting their intended organelles while preserving their physical integrity and functionality. Notably, the intracellular path of the Q-starch/cargo complex is guided by the cargo itself, aligning with its unique biological activity site. This study elucidates the versatility and potency of Q-starch as a versatile drug delivery carrier, paving the way for novel applications offering targeted delivery strategies for potential therapeutic molecules.

DEVELOPMENT OF GASTRORETENTIVE MUCOADHESIVE SOLID DOSAGES FORM CONTAINING AMOXICILLIN TRIHYDRATE AND RANITIDINE HCL FOR THE TREATMENT OF HELICOBACTER PYLORI INFECTIONS

Mucoadhesion can be explored in the design of drug delivery system. Mucoadhesive drug delivery systems interact with the mucus layer covering the mucosal epithelial surface, and mucin molecules, thus increasing the residence time of the dosage form at the site of absorption. The drugs having local action or possessing maximum absorption in gastrointestinal tract (GIT) requires increased duration of stay in GIT. Gastroretentive Mucoadhesive solid dosages form containing Amoxicillin Trihydrate and Ranitidine HCL were formulated to prolong the residence time of the dosage form at the site of application or absorption, and it results in intimate contact of the dosage form with the underline absorption surface. This combination is approved by FDA for the treatment of Helicobacter Pylori Infections. The formulation results in efficient absorption, enhanced bioavailability of the drugs due to a high surface to volume ratio and an improved therapeutic performance of the drug. The prolonged release of drug resulted in reduced frequency of drug administration and improved patient compliance. The optimized formulation was evaluated for various parameters i.e. hardness, friability, thickness, weight variation, drug content, dissolution study and swelling index.