Passive Drug Research Articles

Advances and prospects of precision nanomedicine in personalized tumor theranostics

Tumor, as the second leading cause of death globally, following closely behind cardiovascular diseases, remains a significant health challenge worldwide. Despite the existence of various cancer treatment methods, their efficacy is still suboptimal, necessitating the development of safer and more efficient treatment strategies. Additionally, the advancement of personalized therapy offers further possibilities in cancer treatment. Nanomedicine, as a promising interdisciplinary field, has shown tremendous potential and prospects in the diagnosis and treatment of cancer. As an emerging approach in oncology, the application of nanomedicine in personalized cancer therapy primarily focuses on targeted drug delivery systems such as passive targeting drug delivery, active targeting drug delivery, and environmentally responsive targeting drug delivery, as well as imaging diagnostics such as tumor biomarker detection, tumor cell detection, and in vivo imaging. However, it still faces challenges regarding safety, biocompatibility, and other issues. This review aims to explore the advances in the use of nanomaterials in the field of personalized cancer diagnosis and treatment and to investigate the prospects and challenges of developing personalized therapies in cancer care, providing direction for the clinical translation and application.

Dually functionalized dendrimer for stimuli-responsive release of active ingredients into the skin.

The skin, our largest organ, protects against environmental dangers but is vulnerable to various conditions like infections, eczema, dermatitis, psoriasis, skin cancer, and age-related collagen and elastin degradation. Its outer layer, the water-impermeable epidermis, presents challenges for passive drug delivery to the lower living layers of the skin. An ideal dermal delivery system should penetrate the epidermis and release treatments over time. We report a stimuli-activated nanocarrier that slowly releases active ingredients under skin-specific conditions. Using a fourth-generation polyamidoamine (PAMAM), dendrimer functionalized with poly(2-ethyl-2-oxazoline) and palmitoyl pentapeptide-4, we show a controlled release of biologically active therapeutics into the dermis of the skin for 24 h. Ex vivo studies demonstrate that our nanocarrier system delivers cargo to the dermis and is non-toxic to skin fibroblasts. As a proof of principle, we demonstrate a system that effectively enhances collagen production in human dermal fibroblasts by co-delivering all-trans retinol and palmitoyl pentapeptide-4. Our nanosystem surpasses the effects of individual components. This nanocarrier offers a promising approach for targeted dermal delivery, potentially improving treatment efficacy for various skin conditions while minimizing adverse effects associated with traditional formulations. STATEMENT OF SIGNIFICANCE: In this manuscript we introduce a stimuli-responsive nanocarrier based on a G4-PAMAM dendrimer functionalized with poly(2-ethyl-2-oxazoline) (POZ) and palmitoyl pentapeptide-4, designed to deliver biomolecules specifically to the skin. The nanocarrier enables controlled, stimuli-triggered release under skin-specific conditions (pH 5, 37 °C), enhancing dermal penetration and minimizing release at neutral pH or lower temperatures. This work improves traditional dendrimer systems by reducing toxicity through POZ, ensuring controlled delivery without invasive techniques like iontophoresis, and co-delivering both a small molecule (all-trans-retinol) and a collagen-stimulating peptide for enhanced therapeutic effects. This system addresses major drug delivery challenges, sets a new precedent for safer, multifunctional nanomaterials, and advances dendrimer chemistry, opening new possibilities in targeted therapies, skin treatments, and materials science.

DDEL-09. AS1411 APTAMER-CONJUGATED NANOSPHERES FOR TARGETING GLIOBLASTOMA THERAPY

Abstract Postoperative chemotherapy remains essential for treating glioblastoma (GBM), with nanocarrier-based drug delivery emerging as the most efficient method. However, non-specific delivery across the blood-brain barrier (BBB) can limit drug accumulation in tumors and cause damage to nearby tissues. As cancer progresses, angiogenic processes lead to the formation of an irregular blood-tumor barrier (BTB), necessitating nanodrug platforms for precise targeting and efficient drug delivery to cancer cells. In this study, we aimed to demonstrate targeted cancer therapy by selectively identifying tumor cells overexpressing nucleolin (NCL) protein using Dox-loaded AS1411 aptamer-conjugated nanospheres. Drug nanocarriers were synthesized from small molecules with sizes ranging from 100 to 300 nm to facilitate drug delivery. Selective drug delivery and cellular uptake were demonstrated for NCL-positive GBM cells (U87 and U251) compared to NCL-negative normal human astrocyte (NHA) cells. Flow cytometric analysis using FAM dye-labeled AS1411 aptamer-conjugated nanospheres confirmed that drug delivery to GBM U87 and U251 cells was actively targeted by specific AS1411-NCL interactions. Confocal laser scanning microscopy and cytotoxicity analysis confirmed that inoculation of Dox-loaded AS1411 aptamer-conjugated nanospheres induced selective internalization in GBM U87 and U251 cells. Moreover, to evaluate cytotoxicity and anti-tumor effects after treatment with PBS, Apt-Nanospheres, Free Dox, and Dox-Apt-Nanospheres, the results were analyzed through cell counting kit (CCK-8) analysis, evaluation of differences in 3D tumor sphere radii, and an in vivo GBM xenograft tumor model. The AS1411 aptamer-conjugated nanosphere drug delivery system was developed for dual-target treatment of GBM. AS1411-mediated specific recognition and drug accumulation significantly enhanced binding to NCL-positive U87 and U251 cells and improved cytotoxicity efficiency compared to Free Dox. Additionally, this study demonstrated that the active targeting model using aptamer-mediated drug delivery was more effective in improving drug penetration and retention in tumor cells than non-specific enhanced permeability and retention (EPR)-mediated delivery and passive drug delivery.

Human enteroid monolayers as a potential alternative for Ussing chamber and Caco-2 monolayers to study passive permeability and drug efflux.

After oral administration, the intestine is the first site of drug absorption, making it a key determinant of the bioavailability of a drug, and hence drug efficacy and safety. Existing non-clinical models of the intestinal barrier in vitro often fail to mimic the barrier and absorption of the human intestine. We explore if human enteroid monolayers are a suitable tool for intestinal absorption studies compared to primary tissue (Ussing chamber) and Caco-2 cells. Bidirectional drug transport was determined in enteroid monolayers, fresh tissue (Ussing chamber methodology) and Caco-2 cells. Apparent permeability (Papp) and efflux ratios for enalaprilat (paracellular), propranolol (transcellular), talinolol (P-glycoprotein (P-gp)) and rosuvastatin (Breast cancer resistance protein (BCRP)) were determined and compared between all three methodologies and across intestinal regions. Bulk RNA sequencing was performed to compare gene expression between enteroid monolayers and primary tissue. All three models showed functional efflux transport by P-gp and BCRP with higher basolateral to apical (B-to-A) transport compared to apical-to-basolateral (A-to-B). B-to-A Papp values were similar for talinolol and rosuvastatin in tissue and enteroids. Paracellular transport of enalaprilat was lower and transcellular transport of propranolol was higher in enteroids compared to tissue. Enteroids appeared show more region- specific gene expression compared to tissue. Fresh tissue and enteroid monolayers both show active efflux by P-gp and BCRP in jejunum and ileum. Hence, the use of enteroid monolayers represents a promising and versatile experimental platform to complement current in vitro models.

Dual-trigger release of berberine chloride from the gelatin/perfluorohexane core–shell structure

BackgroundThe development of smart nanocarriers that enable controlled drug release in response to internal and external triggers is an emerging approach for targeted therapy. This study focused on designing pH-sensitive, ultrasound-responsive gelatin/perfluorohexane (PFH) nanodroplets loaded with berberine chloride as a model drug.ResultsThe nanodroplets were prepared using an emulsion technique and optimized by varying process parameters like homogenization rate, polymer concentration, surfactant, drug, and perfluorocarbon content. The optimal formulation yielded nanodroplets with a particle size of 281.7 nm, a drug encapsulation efficiency of 66.8 ± 1.7%, and a passive drug release of 15.4 ± 0.2% within 24 h. Characterization confirmed successful encapsulation and pH-responsive behavior. Ultrasound stimulation significantly enhanced drug release, with 150 kHz being more effective than 1 MHz in triggering acoustic droplet vaporization while minimizing heat generation. After 10 min of radiation, the optimal formulation showed 89.4% cumulative drug release. The nanodroplets displayed stability over 1 month at 4°C.ConclusionsOverall, the dual-triggered nanodroplets demonstrate excellent potential for controlled delivery and targeted release of berberine chloride.Graphical abstract

Progress of nanoparticle drug delivery system for the treatment of glioma.

Gliomas are typical malignant brain tumours affecting a wide population worldwide. Operation, as the common treatment for gliomas, is always accompanied by postoperative drug chemotherapy, but cannot cure patients. The main challenges are chemotherapeutic drugs have low blood-brain barrier passage rate and a lot of serious adverse effects, meanwhile, they have difficulty targeting glioma issues. Nowadays, the emergence of nanoparticles (NPs) drug delivery systems (NDDS) has provided a new promising approach for the treatment of gliomas owing to their excellent biodegradability, high stability, good biocompatibility, low toxicity, and minimal adverse effects. Herein, we reviewed the types and delivery mechanisms of NPs currently used in gliomas, including passive and active brain targeting drug delivery. In particular, we primarily focused on various hopeful types of NPs (such as liposome, chitosan, ferritin, graphene oxide, silica nanoparticle, nanogel, neutrophil, and adeno-associated virus), and discussed their advantages, disadvantages, and progress in preclinical trials. Moreover, we outlined the clinical trials of NPs applied in gliomas. According to this review, we provide an outlook of the prospects of NDDS for treating gliomas and summarise some methods that can enhance the targeting specificity and safety of NPs, like surface modification and conjugating ligands and peptides. Although there are still some limitations of these NPs, NDDS will offer the potential for curing glioma patients.

Bioactive glass beads as a route to passive drug delivery

Bioactive glass beads as a route to passive drug delivery

Human plasma derived exosomes: Impact of active and passive drug loading approaches on drug delivery

The aim of the current study was to explore the potential of human plasma-derived exosomes as versatile carriers for drug delivery by employing various active and passive loading methods. Exosomes were isolated from human plasma using differential centrifugation and ultrafiltration method. Drug loading was achieved by employing sonication and freeze thaw methods, facilitating effective drug encapsulation within exosomes for delivery. Each approach was examined for its effectiveness, loading efficiency and ability to preserve membrane stability. Methotrexate (MTX), a weak acid model drug was loaded at a concentration of 2.2 µM to exosomes underwent characterization using various techniques such as particle size analysis, transmission electron microscopy and drug loading capacity. Human plasma derived exosomes showed a mean size of 162.15 ± 28.21 nm and zeta potential of −30.6 ± 0.71 mV. These exosomes were successfully loaded with MTX demonstrated a better drug encapsulation of 64.538 ± 1.54 % by freeze thaw method in comparison 55.515 ± 1.907 % by sonication. In-vitro drug release displayed 60 % loaded drug released within 72 h by freeze thaw method that was significantly different from that by sonication method i.e., 99 % within 72 h (p value 0.0045). Moreover, cell viability of exosomes loaded by freeze thaw method was significantly higher than that by sonication method (p value 0.0091) suggested that there was membrane disruption by sonication method. In conclusion, this study offers valuable insights into the potential of human plasma-derived exosomes loaded by freeze thaw method suggest as a promising carrier for improved drug loading and maintenance of exosomal membrane integrity.

Nucleolin-Targeting AS1411 Aptamer-Conjugated Nanospheres for Targeted Treatment of Glioblastoma.

Post-operative chemotherapy is still required for the treatment of glioblastoma (GBM), for which nanocarrier-based drug delivery has been identified as one of the most effective methods. However, the blood-brain barrier (BBB) and non-specific delivery to non-tumor tissues can significantly limit drug accumulation in tumor tissues and cause damage to nearby normal tissues. This study describes a targeted cancer therapy approach that uses AS1411 aptamer-conjugated nanospheres (100-300 nm in size) loaded with doxorubicin (Dox) to selectively identify tumor cells overexpressing nucleolin (NCL) proteins. The study demonstrates that the active target model, which employs aptamer-mediated drug delivery, is more effective than non-specific enhanced permeability and maintenance (EPR)-mediated delivery and passive drug delivery in improving drug penetration and maintenance in tumor cells. Additionally, the study reveals the potential for anti-cancer effects through 3D spheroidal and in vivo GBM xenograft models. The DNA-protein hybrid nanospheres utilized in this study offer numerous benefits, such as efficient synthesis, structural stability, high drug loading, dye labeling, biocompatibility, and biodegradability. When combined with nanospheres, the 1411 aptamer has been shown to be an effective drug delivery carrier allowing for the precise targeting of tumors. This combination has the potential to produce anti-tumor effects in the active targeted therapy of GBM.

A Comprehensive Review on Novel Polymer Biomaterials for Hydrogel-Based Drug Delivery System

Abstract: Hydrogel biomaterials, which are formed from polymers generated from either natural or synthetic sources, are characterized by their mechanical stability as well as their biological acceptability. Hydrogels are characterized by properties such as a high swelling index, biocompatibility, the ability to be easily manipulated, flexibility, and rapid degradation. Hydrogels are commonly used as drug carriers due to the fact that they are simple to produce and may be applied by themselves. Using hydrogels in drug delivery applications, where gel-based nanocarriers carry drug molecules to the area of interest in living tissues. The research community is interested in doing this because of the unique physical and chemical properties that hydrogels possess. It has been discussed that several new hydrogel-based solutions are being employed for the administration of drugs that are not taken orally. Hydrogel systems can be developed for use in either passive or active drug administration, making them suitable for a broad variety of settings and applications. In addition to possessing essential biocompatible properties, hydrogels are able to move freely within the human body without having any visible impact on the surrounding environment. The present review has been developed to examine novel concepts linked to hydrogels and their delivery mechanism. This is due to the fact that hydrogels possess qualities that are both unique and novel. In this article, the mechanics of drug delivery systems that are based on hydrogels are detailed. These processes include loading, releasing, and targeting. For these components, the development and investigation of cutting-edge hydrogel- based delivery systems is necessary.

Lack of Effect of Antioxidants on Biopharmaceutics Classification System (BCS) Class III Drug Permeability

The addition of antioxidants to pharmaceutical products is a potential approach to inhibit nitrosamine formation, particularly in solid oral dosage forms like tablets and capsules. The objective was to assess the effect of ten antioxidants on the permeability of four Biopharmaceutics Classification System (BCS) Class III drugs. Bi-directional drug permeability studies in the absence and presence of antioxidants were performed in vitro across MDCK-II monolayers. No antioxidant increased drug permeability, while the positive control sodium lauryl sulfate always increased drug permeability. Results support that any of the ten antioxidants, up to at least 10 mg, can be added to a solid oral dosage form without modulating passive drug intestinal permeability. Additional considerations are also discussed.

The Study of Core–Shell Cobalt Ferrite–Barium Titanate Magnetoelectric Nanoparticles in Targeting and Optimized Drug Delivery: An Overview

This review provides a comprehensive understanding of magnetoelectric (ME) nanocomposite, cobalt ferrite–barium titanate (CFO–BTO) as a potential candidate for targeting specific cells. The synthesized core–shell material uses strain-mediated coupling between magnetostrictive and piezoelectric material. CFO–BTO has the competitive advantage of a high ME coefficient and is biocompatible. The shape and size play a pivotal role in passive drug delivery due to the enhanced permeability and retention effect at tumor sites. Surfactants can also enhance drug absorption and influence the interaction with nanoparticle composite. A comparison between external magnetic field–frequency parameters to navigate the ME nanoparticle and trigger release of the drug at site is also reviewed. Coating the nanoparticles with a layer of surfactant can reduce the threshold external magnetic field for navigation and triggering of drug particle release, making the prospect viable for clinical studies.

A comparative study of passive drug diffusion through human skin via intercellular and sweat duct route: effect of aging.

A method of drug delivery that could provide control over medicine reaching the bloodstream for systemic circulation would be of immense importance. This work presents a comparative study of the temporal and spatial variation of drugs diffusing passively through two separate routes of human skin, namely intercellular (ICR) and sweat duct route (SDR). An analysis is carried out for two age groups (young < 40years and old > 60years of age). Governing equations based on Fick's law for mass transfer have been solved numerically using an in-house developed code. The code has been validated thoroughly with numerical and experimental work from the literature. Each skin route is modeled into three compartments sandwiched between the donor and receiver compartments. To understand the role of diffusion and partition coefficient on drug permeation, four drugs, namely hydrocortisone, trans-cinnamic acid, caffeine, and benzoic acid, are considered. The drug diffusion rate is found greater through ICR as compared to SDR. Further, the amount of drugs diffusing through both routes increases with age. Desirable drug characteristic is inferred to be a lower value of partition coefficient and a higher value of diffusion coefficient. This study could lead to real-time assessment of drugs reaching the bloodstream and beyond.

Free Energy Barriers for Passive Drug Transport through the Mycobacterium tuberculosis Outer Membrane: A Molecular Dynamics Study.

The emergence of multi-drug-resistant tuberculosis strains poses a significant challenge to modern medicine. The development of new antituberculosis drugs is hindered by the low permeability of many active compounds through the extremely strong bacterial cell wall of mycobacteria. In order to estimate the ability of potential antimycobacterial agents to diffuse through the outer mycolate membrane, the free energy profiles, the corresponding activation barriers, and possible permeability modes of passive transport for a series of known antibiotics, modern antituberculosis drugs, and prospective active drug-like molecules were determined using molecular dynamics simulations with the all-atom force field and potential of mean-force calculations. The membranes of different chemical and conformational compositions, density, thickness, and ionization states were examined. The typical activation barriers for the low-mass molecules penetrating through the most realistic membrane model were 6-13 kcal/mol for isoniazid, pyrazinamide, and etambutol, and 19 and 25 kcal/mol for bedaquilin and rifampicin. The barriers for the ionized molecules are usually in the range of 37-63 kcal/mol. The linear regression models were derived from the obtained data, allowing one to estimate the permeability barriers from simple physicochemical parameters of the diffusing molecules, notably lipophilicity and molecular polarizability.

Stimuli‐Responsive Nanocarriers for Transcytosis‐Based Cancer Drug Delivery

Significant challenges persist in enhancing the delivery efficiency of tumor nanomedicines, predominantly due to the difficulty of successfully surpassing pathophysiological barriers. Enhancing tumor penetration of nanomedicines in such conditions represents a pivotal goal in advancing anticancer nanotherapeutics. Transcytosis emerges as a promising solution in this context, addressing the limitations of passive drug delivery. By harnessing diverse stimuli to induce transcytosis, nanocarriers can achieve precise drug delivery and deep tumor penetration, resulting in high therapeutic efficacy and reduced systemic exposure to the therapeutic compound. This review briefly examines various stimuli‐responsive nanosystems and offers an overview and outlook on the development of stimuli‐responsive nanocarriers for transcytosis‐based cancer drug delivery, aiming to provide informative insights for the design of nanomedicines capable of deep tissue penetration and enhanced therapeutic efficacy.

Berberine-styrene-co-maleic acid nanomicelles: unlocking opportunities for the treatment and prevention of bacterial infections.

The global spread of multi-drug-resistant (MDR) bacteria is rapidly increasing due to antibiotic overuse, posing a major public health threat and causing millions of deaths annually. The present study explored the potential of nanocarriers for delivering novel and alternative antibacterial agents using nanotechnology-based approaches to address the challenge of MDR bacteria. The purpose was to enhance the solubility, stability, and targeted delivery of berberine (BER) and its synthetic derivative NR16 using Styrene-co-Maleic Acid (SMA) nanoparticles. Characterization of the nanoparticles, including dynamic light scattering (DLS) analysis, TEM, and UV/Vis absorption spectroscopy, confirmed their suitability and high stability for passive drug delivery. Antibacterial and antifungal activities were evaluated against a panel of pathogens, revealing significant inhibitory effects on Gram-positive strains; particularly BER, SMA-BER, and NR16 were active against MRSA, MSSA, VR, and VS E. faecalis, and S. epidermidis. Additionally, SMA-BER and SMA-NR16 showed promising activity against biofilm formation of S. epidermidis; while the two free drugs contributed to S. epidermidis biofilm disruption activity. Hemolysis tests and in vitro studies on human embryonic kidney cells (HEK-293) confirmed the safety profiles of the nanoparticles and free drugs. Overall, this research highlighted the potential of nanotechnology in developing effective antibacterial agents with reduced toxicity, addressing the growing threat of MDR bacterial infections.

Different Approaches for Transdermal Nano-Carrier Delivery System

Transdermal drug delivery is a validated technology that makes a significant contribution to global pharmaceutical care. Since 1980, the sector has seen impressive growth with several commercial successes. The term transdermal drug delivery refers to the delivery of a drug across the layers of skin with the intention of allowing the drug to be absorbed through the skin in a predetermined and controlled rate manner. Skin is one of the largest organs that act as an efficient barrier for drug delivery. The present study focuses on the different approaches of nano-carrier system that delivers the nano-carrier drug across the skin barrier with the help of transdermal delivery system. Nano-carrier drug delivery systems are one of the biggest challenges to deliver drug into systemic circulation by crossing the skin barrier providing a passive drug delivery strategy that is known to be safer and faster than the conventional method. In this review, we describe the diverse types of nano-carriers approaches that have been synthesized for transdermal delivery system includes liposomes, niosomes, ethosomes, solid lipid nanoparticles (SLN), nanostructured lipid carrier (NLC), polymeric nanoparticles, nanocrystals, nanofibers and nanosuspension/nanoemulsion. Several characterization methods of transdermal delivery system have been proposed to control the behavior of nano-carriers, along with in-vitro and in-vivo and other evaluation parameters. It was concluded that the compatibility of nano-carriers with the skin structure should be considered for transdermal nanocarrier delivery systems, which will be the most preferred route for drug delivery in the future as it offers high patient compliance, controlled dosing, low frequency of dosing, high physico-chemical stability and better dermal bioavailability, etc.

Enhanced topical paromomycin delivery for cutaneous leishmaniasis treatment: Passive and iontophoretic approaches

Conventional treatments for cutaneous leishmaniasis, a neglected vector-borne infectious disease, can frequently lead to serious adverse effects. Paromomycin (PAR), an aminoglycoside antibiotic, has been suggested for the topical treatment of disease-related lesions, but even when formulated in high drug-loading dosage forms, presents controversial efficacy. The presence of five ionizable amino groups hinder its passive cutaneous penetration but make PAR an excellent candidate for iontophoretic delivery. The objective of this study was to verify the feasibility of using iontophoresis for cutaneous PAR delivery and to propose a topical passive drug delivery system that could be applied between iontophoretic treatments. For this, in vitro iontophoretic experiments evaluated different application durations (10, 30, and 360 min), current densities (0.1, 0.25, and 0.5 mA/cm2), PAR concentrations (0.5 and 1.0 %), and skin models (intact and impaired porcine skin). In addition, 1 % PAR hydrogel had its penetration profile compared to 15 % PAR ointment in passive transport. Results showed iontophoresis could deliver suitable PAR amounts to dermal layers, even in short times and with impaired skin. Biodistribution assays showed both iontophoretic transport and the proposed hydrogel delivered higher PAR amounts to deeper skin layers than conventional ointment, even though applying 15 times less drug. To our knowledge, this is the first report of PAR drug delivery enhancement by iontophoresis. In summary, the association of iontophoresis with a topical application of PAR gel seems appropriate for improving cutaneous leishmaniasis treatment.

Preparation and Characterization of Pitavastatin Calcium Loaded Biodegradable Porous Starch as Carrier Platform for Drug Delivery

Introduction: Poor solubility and low oral bioavailability are major obstacles to the development of efficient drug delivery approaches. Numerous chemical entities fall into the biopharmaceutics classification system II (BCS II) class, categorized by low solubility and high permeability. Consequently, finding alternative solutions for improving drug efficacy becomes crucial. Hence, this study aims to formulate biodegradable porous acetostarch (BPSa) and biodegradable porous ethostarch (BPSe) carriers to augment the solubility profile of the poorly soluble drug candidate pitavastatin calcium (PTC). Method: The biodegradable carriers (BPSa and BPSe) were prepared using the solvent exchange method. Then the PTC was loaded into the prepared carriers (PTC@BPSa and PTC@BPSe) using the passive drug loading procedure. Moreover, the obtained drug-carrier conjugates were evaluated using physiochemical evaluation techniques such as Fourier transform infrared spectroscopy (FTIR), x-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC). Additionally, the surface morphology and drug release characteristics are determined. Result: The experimental findings exhibited high drug content with 75.45% and 71.81% for PTC@BPSa and PTC@BPSe, respectively. The SEM analysis of the prepared conjugates demonstrates asymmetrical morphology with cracks between particles, indicating porous nature of the carriers. As a result of this, PTC@BPSa and PTC@BPSe exhibited modified drug release patterns, with cumulative releases of 78.63% and 78.50%, respectively. Conclusion: The biodegradable porous carriers (BPSa and BPSe) effectively improve the dissolution pattern of PTC, by addressing the challenges associated with poor solubility. This study offers valuable insights into the potential of these biodegradable porous carriers as effective drug delivery platforms for increasing the efficacy of limited soluble medications.

Capric Acid and Myristic Acid Permeability Enhancers in Curved Liposome Membranes.

Liposomes are considered as advanced drug delivery systems for cancer treatment. A generation of pH-sensitive liposomes is being developed that use fatty acids (FAs) as a trigger for drug release in tumor tissues. However, FAs are also known to enhance permeability, and it is unclear whether FAs in liposomes may cause drug leakage or premature drug release. The passive permeability of the drug through the membrane of the liposome is thus a crucial factor for timely drug delivery. To investigate how the curvature and lipid composition of liposomes affect their passive permeability, coarse-grained molecular dynamics were performed. The permeability was determined with a counting method. Flat bilayers and three liposomes with varying diameters were studied, which had varying lipid compositions of dipalmitoylphosphatidylcholine, cholesterol, and deprotonated or neutral saturated FAs. The investigated permeants were water and two other small permeants, which have different free energy profiles (solubility) across the membrane. First, for the curvature effect, our results showed that curvature increases the water permeability by reducing the membrane thickness. The permeability increase for water is about a factor of 1.7 for the most curved membranes. However, a high curvature decreases permeability for permeants with free energy profiles that are a mix of wells and barriers in the headgroup region of the membrane. Importantly, the type of experimental setup is expected to play a dominant role in the permeability value, i.e., whether permeants are escaping or entering the liposomes. Second, for the composition effect, FAs decrease both the area per lipid (APL) and the membrane thickness, resulting in permeability increases of up to 55%. Cholesterol has a similar effect on the APL but has the opposite impact on membrane thickness and permeability. Therefore, FAs and cholesterol have opposing effects on permeability, with cholesterol's effect being slightly stronger in our simulated bilayers. As all permeability values were well within a factor of 2, and with liposomes usually being larger and less curved in experimental applications, it can be concluded that the passive drug release from a pH-sensitive liposome does not seem to be significantly affected by the presence of FAs.