Drug Release Kinetics Research Articles

Advancements in Ocular Modelling and Simulations: Key Considerations and Case Studies.

This review paper discusses the key aspects of ocular biopharmaceutics, with emphasis on the crucial role played by ocular compartmental modelling and simulation in deciphering physiological conditions related to various eye diseases. It describes eye's intricate structure and function and the need for precise and targeted drug delivery systems to address prevalent eye conditions. The review categorizes and discusses various formulations employed in ocular drug delivery, delineating their respective advantages and limitations. Additionally, it probes the challenges inherent in diverse routes of drug administration for ocular therapies and provides insights into the complexities of achieving optimal drug concentrations at the target site within the eye. The central theme of this work is the ocular compartmental modelling and simulations. Hence, this works discusses on the nuanced understanding of physiological conditions within the eye, drug distribution, drug release kinetics, and key considerations for ocular compartmental modelling and simulations. By combining information from various sources, this review aims to serve as a comprehensive reference for researchers, clinicians, and pharmaceutical developers. It covers the multifaceted landscape of ocular biopharmaceutics and the transformative impact of modelling and simulation in optimizing ocular drug delivery strategies.

Back Cover: Unveiling the Influence of Oxygen on Drug Release Dynamics in Semipermeable Polymersomes

Back Cover: Unveiling the Influence of Oxygen on Drug Release Dynamics in Semipermeable Polymersomes

Back Cover: Unveiling the Influence of Oxygen on Drug Release Dynamics in Semipermeable Polymersomes

Back Cover: Unveiling the Influence of Oxygen on Drug Release Dynamics in Semipermeable Polymersomes

Nanomedicine in the treatment of Alzheimer's disease: bypassing the blood-brain barrier with cutting-edge nanotechnology.

Alzheimer's disease (AD) remains a formidable challenge in the field of neurodegenerative disorders, necessitating innovative therapeutic strategies. Nanomedicine, leveraging nanomaterials, has emerged as a promising avenue for AD treatment, with a key emphasis on overcoming the blood-brain barrier (BBB) to enhance drug delivery efficiency. This review provides a comprehensive analysis of recent advancements in the application of nanomaterials for AD therapy, highlighting their unique properties and functions. The blood-brain barrier, a complex physiological barrier, poses a significant hurdle for traditional drug delivery to the brain. Nanomedicine addresses this challenge by utilizing various nanomaterials such as liposomes, polymeric nanoparticles, and metal nanoparticles. These nanocarriers enable improved drug bioavailability, sustained release, and targeted delivery to specific brain regions affected by AD pathology. The review discusses the diverse range of nanomaterials employed in AD treatment, exploring their capacity to encapsulate therapeutic agents, modulate drug release kinetics, and enhance drug stability. Additionally, the multifunctionality of nanomaterials allows for simultaneous imaging and therapy, facilitating early diagnosis and intervention. Key aspects covered include the interaction of nanomaterials with Aβ aggregates, the role of antioxidants in mitigating oxidative stress, and the potential of nanomedicine in alleviating neuroinflammation associated with AD. Furthermore, the safety, biocompatibility, and toxicity profiles of various nanomaterials are scrutinized to ensure their clinical applicability. In conclusion, this review underscores the pivotal role of nanomedicine and nanomaterials in revolutionizing AD treatment strategies. By specifically addressing BBB challenges, these innovative approaches offer new avenues for targeted drug delivery and improved therapeutic outcomes in the complex landscape of Alzheimer's disease.

Lipid extract from Black Soldier Fly larvae: A high value excipient for solid lipid nanoparticles tailored to tackle atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a complex pathogenesis involving epidermal barrier dysfunction and aberrant lipid composition, particularly ceramides and fatty acids (FA). Conventional management options, such as topical glucocorticoids (GC), often lead to adverse effects upon prolonged usage, prompting the exploration of alternative therapeutic strategies. The lipid extract from Black Soldier Fly larvae (BSFL) biomass, holding a rich blend of FA, holds substantial potential as a novel ingredient to tackle skin barrier impairment. This study aimed to achieve proof-of-concept validation of innovative nanotechnology-based formulations tailored to enhance the topical management of AD. Specifically, solid lipid nanoparticles (SLNs) with BSFL lipid extract were developed to perform both as a carrier for dexamethasone (DEX), a representative GC, and as skin barrier repair adjuvants. Through systematic optimization using Box-Behnken Design, BSFL lipid extract-based SLNs demonstrated favorable physicochemical properties for topical application and satisfactory stability over 2 months. Notably, these SLNs exhibited favorable drug release kinetics, delivering the total DEX payload within a therapeutically relevant timeframe. Furthermore, these nanocarriers showed the ability to permeate human keratinocytes without pronounced toxicity, suggesting their potential utility in enhancing drug delivery and cellular uptake. Overall, these findings suggest that BSFL lipid extract is a promising natural and sustainable ingredient for the development of nanotechnology-driven approaches to AD management, offering a potential avenue for addressing the unmet needs in this challenging dermatologic condition.

Ultrasound-triggered drug release and cytotoxicity of microbubbles with diverse drug attributes

Ultrasound (US)-triggered cavitation of drug-loaded microbubbles (MBs) represents a promising approach for targeted drug delivery, with substantial benefits attainable through precise control over drug release dosage and form. This study investigates Camptothecin-loaded MBs (CPT-MBs) and Doxorubicin-loaded MBs (DOX-MBs), focusing on how properties such as hydrophilicity, hydrophobicity, and charged functional groups affect their interaction with the lipid surfaces of MBs, thereby influencing the fundamental characteristics and acoustic properties of the drug-loaded MBs. In comparison to DOX-MBs, CPT-MBs showed larger MB size (2.2 ± 0.3 and 1.4 ± 0.1 μm, respectively), a 2-fold increase in drug loading, and an 18 % reduction in leakage after 2 h at 37℃. Under 1 MHz US with a 100 ms pulse repetition interval (PRI), 1000 cycles, 5-minute duration, and 550 kPa acoustic pressure, CPT-MBs undergo inertial cavitation, while DOX-MBs undergo stable cavitation. Drug particles released from these MBs under US-induced cavitation were analyzed using dynamic light scattering, NanoSight, cryo-electron microscopy, and density gradient ultracentrifugation. Results showed that CPT-MBs mainly release free CPT, while DOX-MBs release multilayered DOX-lipid aggregates. The cytotoxicity to C6 cells induced by US-triggered cavitation of these two types of MBs also differed. DOX-lipid aggregates delayed initial uptake, leading to less pronounced short-term (2 h) effects compared to the rapid release of free CPT from CPT-MBs. These findings underscore the need to optimize drug delivery strategies by fine-tuning MB composition and US parameters to control drug release kinetics and achieve the best tumoricidal outcomes.

Biocompatibility and drug release kinetics of TiNbZrSn femtosecond laser-induced superhydrophilic structures

As load-bearing components, metallic implants are frequently used for orthopedic prostheses due to their superiority over conventional ceramic and polymeric biomaterials. Metal-based orthopedic implants have been subjected to various fabrication and treatment methods to enhance their biological activities at the host site. Modifying the structure, improving the hydrophilicity, and developing controlled-release drug delivery systems can improve cellular adhesion, proliferation, osseointegration, and differentiation. Ultrafast lasers have recently attracted interest in surface engineering. Laser surface structuring permits the alteration of sample topography, the chemical makeup of the surface, and the material physical properties. This study presents the surface modification of a TiNbZrSn shape memory alloy using a femtosecond laser to produce laser-induced periodic structures with better drug release than that of a pristine sample. We also present the in vitro cell viability and biocompatibility of the alloy system. All samples structured with femtosecond laser exhibited superhydrophilic nature with 0° contact angle. In addition, the laser structured surfaces showed cell viability above 80 % and minimal cytotoxicity towards human keratinocytes. Moreover, a well-defined hydroxyapatite layer developed on the laser structured surface. In general, the laser structuring process and the induced changes on the surface in terms of roughness and oxide formation result in slower drug release (up to 10 %) compared to pristine specimens.

Alginate Microbeads Technology for Pharmaceutical Applications

Nowadays, microbeads are inevitable in pharmaceutical formulations with remarkable drug delivery and therapeutic outcome benefits. Usually made from biocompatible polymers, these tiny spherical particles allow for controlled and targeted delivery of APIs within the human body. Other benefits associated with microbeads include their ability to control drug release kinetics in terms of sustained or pulsatile release profiles in order to facilitate patient compliance and minimize adverse effects. This also has a minimal size and allows for adaptation for precise dosing and targeting the right sites, which augments therapeutic efficacy while cutting down systemic exposure. The need for safe and effective drug delivery systems has been a crucial aspect in the advancement of new pharmaceutical formulations. Researchers continue to seek new ways in prolonging drug release, minimizing drug wastage, and reducing the side effects of drugs. However, synthetic polymers are costly, non-biocompatible, and potentially toxic. On the other hand, sodium alginate, a natural polymer, is generally used as a matrix material because of biodegradability, low price, simplicity, and excellent biocompatibility. Sodium alginate is nontoxic when delivered orally and gives protection on the mucous membrane of the upper gastrointestinal tract. Sodium alginate is an anionic polysaccharide of natural origin wherein gelation can be obtained with the use of calcium ions to form stable microbeads. There are multiple techniques used to prepare alginate microbeads, that is, ionotropic gelation, cross-linking, emulsion gelation, spray drying, and both simple and complex coacervation phase separation methods. This review shall highlight the preparation and characterization of alginate microbeads, their therapeutic applications, and their position in the realm of controlled and novel drug delivery systems

Exploring the potential of a pH-sensitive hydrogel sponge: interpenetrating network of tragacanth and pectin for controlled delivery of levosulpiride.

The development of drug delivery systems that allow precise control over drug release pattern has fetched significant attention in the pharmaceutical field. This research work investigates the potential of a pH-sensitive interpenetrating network (IPN) composed of tragacanth and pectin as a carrier for the controlled release of levosulpiride. To enhance the solubility of poorly soluble drug levosulpiride, inclusion complexes were formed with beta cyclodextrin (βCD). The IPN was prepared by cross-linking tragacanth with pectin by adopting a green chemistry approach. The resulting cross-linked polymeric network was subjected to repetitive freeze-drying cycles for preparation of spongy mass. The physicochemical properties of the resultant product were thoroughly characterized using a range of analytical techniques, including Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), thermal analyses (DSC/TGA), and X-ray diffraction (XRD). The physical parameters like sol-gel fraction (%), drug loading (%), swelling behavior, electrolyte responsiveness, and in vitro drug release profile of the developed sponge were systematically evaluated under varying pH conditions. Results of FTIR demonstrated the formation of cross-linked network, ruling out drug-excipient interaction. SEM analysis unveiled porous and rough geometry. Thermal analyses proved the hydrogel network thermally stable whereas, PXRD demonstrated the overall amorphous nature of the hydrogel sponge. The outcomes of physical parameters demonstrated an incremental trend in gel fraction from 63 to 85% on raising the molar concentration of cross-linker from TP1 to TP3. However, increasing tragacanth content escalation in gel fraction from 75 to 79% was noticed. While gel fraction was augmented from 79 to 83% with increasing pectin contents. The maximum drug loading formulation TP3 was computed to be 89%. Hydrogel sponges also demonstrated electrolyte responsiveness. The release profile indicated a pH-responsive behavior, with sustained release up to 10h observed in a buffer solution of pH 6.8 and 7.4. In an acidic medium, a minor amount of drug was released during 10h dissolution. Drug release kinetics was observed to be in zero order. The findings of this study highlight the promising potential of the tragacanth/pectin hydrogel sponge as a pH-sensitive dais for the controlled delivery of levosulpiride, emphasizing its potential application in personalized drug therapy and the treatment of gastrointestinal disorders.

The upconversion luminescence biomonitoring and biological properties of rare earth oxide-inorganic composite microspheres enhanced by lithium

Multiple myeloma is the second most common hematologic malignant tumor, which can result in complications such as osteolytic fractures and bacterial infections. The side effects of chemotherapy limit the dosage of drugs, which can easily lead to multidrug resistance. Moreover, the dose and distribution of drugs within the body significantly influence the therapeutic efficacy of drugs. Therefore, it is highly necessary to improve multidrug resistance and bacterial infection in the treatment of multiple myeloma, repair bone defects caused by bone pain, and monitor the real-time dynamics of drugs. This work proposes a novel rare earth oxide-inorganic composite (7Li-MBGs:2Er/2Yb-0.75MTO) as a drug delivery platform for the treatment of multiple myeloma. 7Li-MBG, which have bone repair functions, serve as inorganic matrix materials, while Er2O3 and Yb2O3 act as activators and sensitizers, respectively. MTO is used as a therapeutic drug for treating myeloma. The drug release process of MTO was successfully monitored by upconversion luminescence. Cell experiments confirmed that 7Li-MBGs:2Er/2Yb-0.75MTO has a certain long-term therapeutic effect on multiple myeloma, and its mechanism of action is consistent with its drug release kinetics. Moreover, the synergistic effect of rare earth oxides, alkali metal ions and MTO endows 7Li-MBGs:2Er/2Yb-0.75MTO with high antibacterial and osteoinductive abilities, and thus playing a role in enhancing the drug resistance of infectious bacteria, preventing bacterial infection, repairing bone defects and monitoring the real-time dynamics of drug release during multiple myeloma therapy. Therefore, the 7Li-MBGs:2Er/2Yb-0.75MTO multifunctional drug delivery platform synthesized in this work provides a new idea for the treatment of multiple myeloma and biomonitoring.

Antibacterial and Anti-Inflammatory Activity of Chitosan Film with Rhodomyrtus Tomentosa Leaf Extract Prepared Via 3D-Printing Method.

The combination of natural polymers and plant extract attracted much attention thanks to its valuable biological activities. This study presents the preparation and characterization of chitosan (CS) film containing Rhodomyrtus tomentosa leaf extract. In which, the Rhodomyrtus tomentosa leaf extract (SLE) with polyphenol-rich fractions was extracted by an ultrasonic-assisted extraction method. The prepared chitosan/polyphenol-rich fractions film (CSPPF) was characterized using infrared (IR) spectroscopy, mechanical testing, scanning electron microscopy (SEM), and water absorption analysis. Antibacterial and anti-inflammatory activities of the CSPPF were assessed using the agar well diffusion method and nitric oxide (NO) inhibition assays, respectively. Besides, the release of the extract from the CSPPF as well as the drug release kinetics was also tested. The Rhodomyrtus tomentosa leaf extract enhanced the antibacterial efficacy against Escherichia coli and enhanced the anti-inflammatory activity as well as the swelling ability of the CSPPF. The CSPPF containing 1 wt.% of SLE can inhibit 77.70 % NO with an IC50 value of 19.40 μg/mL.

Hyaluronan-Cholesterol nanogels embedding betamethasone for the treatment of skin inflammatory conditions

Topical application of the glucocorticoid betamethasone (BM) is a common treatment for inflammatory-related skin diseases, such as psoriasis. However, enhancing its bioavailability remains challenging due to poor skin permeability. Herein, we developed and evaluated hyaluronan-cholesterol (HACH) based nanohydrogel systems (NHs) and NHs-Carbopol formulation for dermal delivery of BM. Various parameters were investigated including particle size, surface charge, encapsulation efficiency, in vitro drug release kinetics and stability. The HACH-based NHs demonstrated high encapsulation efficiency, with apparent solubility improved up to 9-fold, small size (∼190 nm) and good stability at 4 ℃ and during long-term storage. Besides, the NHs-Carbopol formulation exhibited excellent rheological properties and an occlusive effect suitable for cutaneous application. Both in-vitro (using Strat-M® membrane) and ex-vivo (using pig ear skin) permeation studies revealed that these formulations significantly improved skin permeation and drug retention in the deeper layers of the epidermis and dermis, making it advantageous for the topical delivery of BM in psoriasis treatment. Moreover, the NHs system demonstrated potential anti-psoriatic activity by downregulating the proinflammatory cytokines in vitro in human keratinocytes (HaCaT cell line) and in an ex vivo 3D skin tissue model (EpiDerm-FT™).

In vitro comparative quality evaluation of different brands of Amlodipine Tablets Commercially available in Jimma Town, South-western Ethiopia.

The incidence of hypertension in persons 25 years of age and older is estimated to be 46% in Africa, where it is still very common. This concerning rate could be explained by the pharmaceutical markets' accessibility to poor quality antihypertensive drugs. Thus, the purpose of this study was to evaluate and compare the quality different brands of Amlodipine Tablets Commercially available in Jimma Town, South-western Ethiopia. The quality control test was conducted from August 30, 2019 to February 27, 2020 at Jimma University in the Laboratory of Drug Quality Control (JuLaDQ). The laboratory test was carried out in accordance with WHO inspection guidelines and United States Pharmacopeia. A statistically significant was considered when P<0.05. For further comparison of the in-vitro dissolution profiles of amlodipine tablets, model-independent model-dependent parameters and statistical Dunnetts tests for ensuring bioequivalence were used to further compare the in-vitro dissolution profiles. With the exception of brand AMD-5 (1/10), the remaining nine (n = 9) brands were within WHO visual inspection criteria. The quality control parameters such as friability, weight variation, identity, assay, and dissolution test were within the United States Pharmacopeia. The model independent parameters (f1, and f2) confirmed that, all generic products were bio-equivalence, and interchangeable with comparator product. The model dependent approaches revealed the Weibull model (AMD-10), the Zero order (AMD-3), and the Korsemeyer-Peppas models were the most effective predictions for the release of the pharmaceutical substance from the dosage form. The Korsemeyer-Peppas model (r2 ≥0.9695) was the best descriptive model for determining the amlodipine drug kinetics from the point of view of all brands examined. The evaluated amlodipine brand tablets were in line with quality standards. The model independent methods confirmed that the generic brand tablets were interchangeable in clinical practice. The tested products follow more than two drug release kinetics. The study revealed a manifest discrepancy in the dissolution profiles' releases. Therefore, it is strongly advised to use appropriately designed dissolution profile evaluation methods with various pH values in the dissolution media, as well as to do comprehensive visual inspections. This will make it easier to do a thorough investigation of any potential quality issues that might be related to various generic products available in the pharmaceutical market.

Modular Synthetic Platform to Tailor Therapeutic-Specific Delivery in Injectable Hydrogels.

Injectable thermoresponsive hydrogels (thermogels), valued for their conformability and minimal invasiveness, are increasingly used as in situ forming implants for drug delivery and as regenerative scaffolds. These gels exhibit sol-to-gel phase transitions at body temperature. As localized depots and scaffolds, these gels determine the chemical and mechanical environments and could dramatically influence the release kinetics of drugs or the fate of cells. Current synthetic approaches for thermogels, however, often limit the ability to fully exploit interactions between the thermogel matrix and the encapsulated agent. In this study, we introduce a modular synthetic platform for creating a library of functionalized polyurethane thermogels that enables customization of gelation properties and intermolecular interactions. These thermogels can exhibit a wide range of stiffness, offer complementary ionic interactions, and enhance hydrophobic interactions and hydrogen bonding. By leveraging these tunable interactions between the thermogelling scaffold, functional groups, and encapsulated agents, we achieved sustained and controlled release, from days to over 6 months, for both low and high molecular weight drug analogs. Release profiles varied from monophasic to biphasic and triphasic depending on the compatibility between the thermogel properties and the encapsulated agents. The design rules identified here support the development of drug-specific formulations, facilitating precise, sustained, and modulated release tailored to therapeutic needs. Beyond providing an adaptable strategy for customizable injectable drug depots, this synthetic strategy lays the groundwork for future iterations of multi stimuli-responsive thermogels with enhanced bioactivity, advancing the potential for customizable, biointeractive therapeutic systems.

Formulation, Characterisation, and Biocompatibility Assessment of Rifampicin-Loaded Poly(d,l-lactide-co-glycolide) Composites for Local Treatment of Orthopaedic and Wound Infections.

Background/Objectives: The escalating challenge of antimicrobial resistance (AMR) necessitates the development of targeted antibiotic delivery platforms, minimising systemic administration. Polymer-based drug delivery emerges as a promising solution, ensuring sustained release and prolonged efficacy of bioactive compounds, ensuring long-term efficacy. Methods: This study focuses on encapsulating rifampicin (RIF), a key antibiotic for orthopaedic and wound-related infections, within Poly(d,l-lactide-co-glycolide) (PLGA), a biodegradable polymer, through solvent casting, to formulate a PLGA-RIF composite membrane. Comprehensive characterisation, employing Fourier-transformed infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), thermal analysis and X-ray Diffraction (XRD), confirmed the integrity of both the starting and produced materials. UV-Vis spectroscopy revealed a controlled drug release profile over 21 days in various media, with the chosen media influencing the drug release, notably the tryptic soya broth (TSB) caused the highest release. The quantitative assessment of the antimicrobial efficacy of the developed PLGA-RIF composite was conducted by measuring the size of the inhibition zones against both Gram-negative and Gram-positive bacteria. Results: The results confirmed the composite's potential as a robust antibacterial biomaterial, demonstrating a rapid and effective antibacterial response. Cytocompatibility tests incorporated human fibroblast and osteoblast-like cell lines and demonstrated that the RIF:PLGA (1:8) formulation maintained eukaryotic cell viability, indicating the composite's potential for targeted medical applications in combating bacterial infections with minimal systemic impact. Conclusions: This study presents the significance of investigating drug release within appropriate and relevant physiological media. A key novelty of this work therefore lies in the exploration of drug release dynamics across different media, allowing for a comprehensive understanding of how varying physiological conditions may influence drug release and its effect on biological responses.

Drug release kinetics from in-situ modulated agar/chitosan-bacterial cellulose patches for differently soluble drugs

Bacterial cellulose (BC) stands out as a promising candidate for novel drug delivery systems due to its micro-mesoporous nanofibrous interconnected structure. However, its performance is limited by the burst release of hydrophilic drugs and lower incorporation of the less water-soluble or insoluble drugs. In this study, we explored its potential as a drug carrier for two distinct types of drugs: Diclofenac sodium and Simvastatin, representing water-soluble and water insoluble compounds, respectively. To tune the morphology and drug-BC interaction, agar and chitosan were introduced into the culture medium during BC synthesis for in-situ modification. These modulated BCs are characterized and further analyzed through drug release studies and mathematical modeling to understand the mechanisms and key factors controlling the drug release behavior. Incorporating agar and chitosan into the BC network results in changes to its microstructure and crystallinity, which in turn affects the overall swelling, drug loading and release properties. Our results revealed that the BC followed a first-order quasi-Fickian kinetics for water-soluble drug and non-Fickian release mechanism for water-insoluble drug. In contrast, agar-modulated BC (A-MBC) demonstrated a non-Fickian first-order diffusion kinetics, with slow release for water-soluble drug and sustained release for the water-insoluble drug due to the higher density which impedes drug release. Chitosan-modulated BC (C-MBC) exhibited non-Fickian first-order kinetics, with slower release for water soluble drug. Further, C-MBC exhibited extended release for water insoluble drug to over 14 days, following first-order kinetics for the first 12 h, then transitioning to zero-order kinetics with a Case II release mechanism, attributed to drug-matrix interactions. These findings successfully demonstrate the possibility to tailor BC thus the release kinetics for both water-soluble and less soluble or insoluble drugs.

Cryostructuring of Polymeric Systems: 68. Evaluation of Poly(vinyl alcohol) Composite Cryogels Filled with Poly(3-hydroxybutyric acid)-Based Microspheres of Different Porous Morphology as Potential Delivery Systems for Drugs of Various Water-Solubility.

Poly(3-hydroxybutyric acid)-based microspheres of two types, with and without macropores, were prepared; their morphology and particle size were evaluated. These microspheres were entrapped as disperse fillers into the bulk of macroporous cryogels based on poly(vinyl alcohol) (PVA). It was found that the rigidity of the resultant composite cryogels increased markedly as compared to that of unfilled cryogels of the same PVA concentration. The resulting composites were further tested for their potential to act as drug carriers. With that, simvastatin was included into the filler particles directly in the course of their preparation, followed by entrapment of such drug-loaded microspheres into the PVA cryogel. In turn, ibuprofen sodium salt was introduced into the preliminary prepared cryogels filled with the drug-free microspheres. The experimental study of drug release kinetics showed that due to the non-covalent interactions of both simvastatin and ibuprofen sodium salt with the particles of discrete phase, prolongation of the release processes was observed.

A Coarse-Grained Molecular Dynamics Perspective on the Release of 5-Fluorouracil from Liposomes.

Liposomes, small bilayer phospholipid-containing vesicles, are frequently used to ensure slow drug release for a prolonged and improved therapeutic effect. Nevertheless, current findings on the membrane affinity and permeability of the anticancer agent 5-fluorouracil (5-FU) are confounding, which leads to a lack of a clear understanding of how lipid composition impacts the distribution of 5-FU within liposomal structures and its delivery. In the current work, we report a comprehensive coarse-grained molecular dynamics (CGMD) investigation on the influence of cholesterol (CHOL) and the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) on the partitioning of 5-FU in 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) double-bilayer systems, as well as its in vitro release from liposomes with identical lipid compositions. Our results show that 5-FU tends to accumulate at the water-lipid interface, in the vicinity of polar headgroups, without partitioning in the hydrophobic tail region. At the same time, the presence of CHOL proportionally increases the distribution of this drug in the interbilayer aqueous space, decreasing the drug's affinity toward the membrane polar head region, while DOTAP has only a slight effect on drug distribution. Thus, it is expected that 5-FU will be released slower from CHOL-containing DPPC liposomes but not DOTAP-containing vesicles. However, in vitro release studies showed that the release kinetics of 5-FU from DPPC vesicles is not influenced by the presence of CHOL and that the incorporation of 10 mol % DOTAP leads to the best release profile for 5-FU, highlighting the complexity of nanocarrier drug release kinetics. We hypothesize that the initial rapid release seen in dialysis experiments is not related to drug membrane permeability but rather to 5-FU adsorbed on the outer surface of liposomes.

OPTIMIZED SOLID LIPID NANOPARTICLES FOR ENHANCED ORAL BIOAVAILABILITY AND OSTEOGENIC EFFECT OF IPRIFLAVONE: FORMULATION, CHARACTERIZATION, AND IN VITRO EVALUATION

Objective: This study aimed to enhance the oral bioavailability of Ipriflavone (IP) and evaluate its osteogenic effect on human osteosarcoma cells (MG-63) by developing Ipriflavone-loaded Solid Lipid Nanoparticles (IP-SLN). Methods: IP-SLNs were prepared using a modified solvent evaporation method with probe sonication. Formulation optimization employed Central Composite Design (CCD) with independent variables, including lipid amount, surfactant concentration, and sonication time. Characterization was performed using Transmission Electron Microscopy (TEM). In vitro drug release and ex vivo permeation studies were conducted to assess drug release kinetics and bioavailability. Cytotoxicity, Alkaline Phosphatase (ALP) activity, and calcium deposition studies on MG-63 cells evaluated osteogenic effects. Results: TEM images showed round particles with an average diameter of 43.24±3 nm, a zeta potential of-9.53 mV, and a drug entrapment efficiency of 76.53±1.84%. In vitro drug release from IP-SLN was 79.02% compared to 14.21% from IP after 48 h, following the Korsmeyer-Peppas model and first-order kinetics. Ex vivo permeation of IP-SLN was approximately 2-fold higher than IP dispersion. Cytotoxicity studies revealed no toxicity on MG-63 cells. ALP activity and calcium deposition studies indicated that IP-SLN stimulated osteoblast differentiation, increasing alkaline phosphatase activity and mineralization. Pharmacokinetic studies demonstrated that IP-SLN increased the relative bioavailability by 515% compared to ipriflavone. Conclusion: IP-SLN formulations significantly improved the oral bioavailability and osteogenic effects of ipriflavone on MG-63 cells, suggesting potential for novel therapeutic applications in osteoporosis treatment.

Recent Advances, Challenges, Future Direction of Drug Delivery System in Nanotechnology

Although there are a number of obstacles to overcome, the field of improved drug delivery systems has bright future prospects in pharmacology. Overcoming biological barriers, guaranteeing stability and biocompatibility, delivering targeted delivery, and navigating regulatory obstacles are some of the challenges. Prospective avenues for advancement encompass the amalgamation of nanotechnology, biomaterials, and customized medicine methodologies, the amplification of non-invasive delivery techniques, and the augmentation of drug release kinetics. By increasing efficacy and reducing adverse effects, these developments seek to transform medication therapy and eventually improve patient outcomes