Drug Delivery Approaches Research Articles

Formulation and Evaluation of Gel Containing Nigella sativa Seed Extract Loaded Transferosomes for Effective Treatment of Psoriasis

Background: Psoriasis vulgaris is an autoimmune associated skin disease causing plaques or scales formation where the skin cells form quicker than in their typical life cycle. The phenolic phytoconstituents reported in Nigella sativa are effective for the treatment of skin disorders. Transfersomes is an emerging nanoencapsulation drug delivery approach which can squeeze themselves due to its elastic nature as an intact vesicle across narrow pores. It improves the potency of topical formulations with higher permeation efficiencies compared to other vesicular drug delivery systems. Objective: This research work focused to prepare Nigella sativa or black seed extract loaded transfersomes as nanoformulation and further incorporating them in the gel system to give improved therapeutic efficacy due to their self-regulating and self-optimizing capabilities. Methods: The phenolic content of Nigella sativa or black seed was extracted in ethanol and the solvent was removed using a vacuum with suitable storage conditions at 22ºC. Transfersomes of ethanol extract were prepared by thin layer hydration method and further incorporated into gel formulations. The ant-psoriasis activity of prepared gel formulation was performed with histopathology study in the Imiquimod induced albino rat model. Results: A nanoformulation prepared with 0.85 mg lecithin and 0.10 mg tween 80 has the highest entrapment efficiency. The entrapment efficiency, vesicle size, polydispersity index and zeta potential of optimized transferosomes batch were found to be 69.3 ± 2.6%, 178 ± 11 nm, 1.1 ± 0.2, -29.4 mV, respectively. Anti-psoriatic activity of N. sativa seed extract loaded transfersomes showed a more significant reduction in thickness of the epidermis and less elongation of rete ridges with capillary loop dilation as compared to conventional gel formulation. Conclusion: We concluded that the Nigella sativa seed ethanolic extract loaded transfersomes gel formulation showed significant ant-psoriasis activity in an albino rat model.

Electrospinning polymersomes into bead-on-string polyethylene oxide fibres for the delivery of biopharmaceuticals to mucosal epithelia

Fibrous mucoadhesive polymer membranes prepared using electrospinning demonstrate many advantages for mucosal drug delivery compared to other formulations. Previous electrospun membrane formulations have been developed mainly for the delivery of small molecule drugs. There remains great potential to further develop the technology for the delivery of vesicular vectors that allow administration of advanced therapeutic agents. However, there are no previous reports demonstrating the release of intact drug delivery vesicles from electrospun materials. Here, we describe incorporation and release of protein-loaded polymersomes from polyethylene oxide (PEO)-based electrospun membranes. Polymersomes comprising a copolymer of glycerol monomethacrylate (GMA) and hydroxypropyl methacrylate (HPMA) were prepared using polymerization-induced self-assembly and incorporated within PEO membranes using bead-on-string electrospinning at approximately 40 % w/w by polymer mass. Super-resolution fluorescence imaging showed that the vesicles remained intact and retained their encapsulated protein load within the fibre beads. Transmission electron microscopy and dynamic light scattering demonstrated that polymersomes retained their morphology following release from the polymer fibres. F(ab) antibody fragments were encapsulated within polymersomes and then electrospun into membranes. 78 ± 13 % of the F(ab) remained encapsulated within polymersomes during electrospinning and retained functionality when released from electrospun membranes, demonstrating that the formulation is suitable for the delivery of biologics. Membranes were non-irritant to the oral epithelium and fluorescence microscopy detected accumulation of polymersomes within the epithelia following application. This innovative drug delivery approach represents a novel and potentially highly useful method for the administration of large molecular mass therapeutic molecules to diseased mucosal sites.

Unraveling the role of glial cell line-derived neurotrophic factor in the treatment of Parkinson's disease.

Parkinson's disease is the second most common neurodegenerative condition with its prevalence projected to 8.9 million individuals globally in the year 2019. Parkinson's disease affects both motor and certain non-motor functions of an individual. Numerous research has focused on the neuroprotective effect of the glial cell line-derived neurotrophic factor (GDNF) in Parkinson's disease. Discovered in 1993, GDNF is a neurotrophic factor identified from the glial cells which was found to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. Given this property, recent studies have focused on the exogenous administration of GDNF for relieving Parkinson's disease-related symptoms both at a pre-clinical and a clinical level. This review will focus on enumerating the molecular connection between Parkinson's disease and GDNF and shed light on all the available drug delivery approaches to facilitate the selective delivery of GDNF into the brain paving the way as a potential therapeutic candidate for Parkinson's disease in the future.

Block Copolymer‐Stabilized Metal–Organic Framework Hybrids Loading Pd Nanoparticles Enable Tumor Remission Through Near‐Infrared Photothermal Therapy

Metal–organic frameworks (MOFs), such as the magnetic resonance imaging‐fit MIL‐100 based on Fe, are gaining significant attention as versatile theranostics with high‐loading capability. Moreover, as MOFs can be engineered to target tumors, there is much interest in applying them for precise pin‐point treatment of cancer. Herein, Pd nanoparticles within MIL‐100(Fe) are generated to create MOFs with remarkable photothermal conversion properties for cancer therapy. The Pd‐loaded MIL‐100(Fe) (Pd@MIL‐100(Fe)) are stabilized with biocompatible block copolymers to generate MOFs with PEGylated surfaces. This is achieved by directly mixing poly(ethylene glycol)‐poly(L‐aspartic acid) (PEG‐p(Asp)) or dopamine‐modified PEG‐p(Asp) (PEG‐p(Asp‐Dopa)) block copolymers with the MOFs in aqueous conditions. The resulting block copolymer‐stabilized MOF hybrids are stable in physiological conditions. Particularly, the Pd@MIL‐100(Fe)/PEG‐p(Asp‐Dopa) hybrids show enhanced blood circulation and increased accumulation in B16F10 melanoma. Furthermore, when irradiated with 808 nm light, the Pd@MIL‐100(Fe)/PEG‐p(Asp‐Dopa) hybrids rapidly increase the temperature to 50 °C, enabling tumor remission. The surface‐stabilized Pd@MIL‐100(Fe)/polymer hybrids open viable opportunities for innovating MOF/polymer hybrid‐based approaches for drug delivery.

Ligand-mediated Targeted Drug Delivery Approaches against Hepatocellular Carcinoma.

One of the most important health problems in the world today is cancer. The World Health Organization (WHO) reported that it results in 8.9 million deaths annually. Malignant tumours and unregulated cell proliferation are features of malignant neoplasms, which can also invade nearby body regions. Hepatocellular carcinoma is the third most prevalent cause of cancer-related death worldwide and the fifth most common kind of cancer, according to a recent analysis. Patients with liver disease as well as chronic hepatitis B and C are more likely to develop hepatocellular carcinoma (HCC). Physical barriers, including RES absorption, opsonization, and first-pass drug metabolism, make drug therapy more challenging. Conventional cancer therapy procedures have a low response rate or may continue to be unsuccessful due to multi-drug resistance (MDR), high clearance rates, and other side effects because of suboptimal drug distribution and insufficient drug concentration reaching cancer cells. Innovative target drug molecules that are tailored to the injured liver cells must be developed in order to improve medication administration and drug targeting. The use of targeting ligands that have been joined to drug molecules or nanocarriers forms the basis of innovative targeting techniques. After being conjugated with the treatment method, ligands for targeting hepatocellular carcinoma cells included asialoglycoprotein, galactoside, lactobionic acid, mannose-6-phosphate, PDGF, antibodies, and aptamers.

Proliposomal Formulation: A safer and effective approach for drug delivery with special mention to NSAIDS

Proliposomes formulations have shown their importance and significance for the efficient delivery of medicament, especially in those cases where liposomal preparations are required with more stability. These are freely flowable powder preparation where a drug entangled with lipid and cholesterol is deposited over water-soluble carrier material which get converted into liposomes after dispersion in suitable media in-vitro or in-vivo. In past decades, several studies have been published regarding the safer and more effective use of Proliposomes for the administration of drugs via different routes such as oral, transdermal, vaginal etc. It has also been noted that they show their more utility for oral administration of drugs like NSAIDs where gastric absorption, bioavailability, and GI toxicity is a major concerns. The current review includes the various methods used for the pro-liposome preparation, methods to be used for its evaluation along with the application of proliposomes preparation for different purposes and routes of administration. It also includes a summary of work related to the pro-liposomes formulation development of NSAIDs.

2D Materials for Combination Therapy to Address Challenges in the Treatment of Cancer

2D materials exhibit a variety of characteristics that make them appealing platforms for cancer treatment such as high drug loading capacity and photothermal and photodynamic properties. A key advantage of 2D material platforms for oncological applications is the ability to harness multiple modalities including drug delivery, photothermal therapy, photodynamic therapy, chemodynamic therapy, gene delivery, and immunotherapy approaches for improved efficacy. In this review, a comparison of the unique properties of different classes of 2D materials that enable their usage as platforms for multimodal therapy is provided. Further, the benefits and drawbacks of different platforms are also highlighted. Finally, current challenges and emerging opportunities for future development of 2D materials to further enable combination therapy and translation from the bench to clinical oncology applications are discussed.

3D printing injectable microbeads using a composite liposomal ink for local treatment of peritoneal diseases

The peritoneal cavity offers an attractive administration route for challenging-to-treat diseases, such as peritoneal carcinomatosis, post-surgical adhesions, and peritoneal fibrosis. Achieving a uniform and prolonged drug distribution throughout the entire peritoneal space, though, is difficult due to high clearance rates, among others. To address such an unmet clinical need, alternative drug delivery approaches providing sustained drug release, reduced clearance rates, and a patient-centric strategy are required. Here, we describe the development of a 3D-printed composite platform for the sustained release of the tyrosine kinase inhibitor gefitinib (GEF), a small molecule drug with therapeutic applications for peritoneal metastasis and post-surgical adhesions. We present a robust method for the production of biodegradable liposome-loaded hydrogel microbeads that can overcome the pharmacokinetic limitations of small molecules with fast clearance rates, a current bottleneck for the intraperitoneal (IP) administration of these therapeutics. By means of an electromagnetic droplet printhead, we 3D printed microbeads employing an alginate-based ink loaded with GEF-containing multilamellar vesicles (MLVs). The sustained release of GEF from microbeads was demonstrated. In vitro studies on an immortalized human hepatic cancer cell line (Huh-7) proved concentration-dependent cell death. These findings demonstrate the potential of 3D-printed alginate microbeads containing liposomes for delivering small drug compounds into the peritoneum, overcoming previous limitations of IP drug delivery.Graphical abstract

Microneedles: A Novel Approach in Transdermal Drug Delivery: Review Paper

Transdermal drug delivery systems (TDDS) are a focus of drug delivery research due to their distinct advantages over oral and parenteral drug delivery systems. Researchers have focused on the use of microneedles to break through the stratum corneum barrier. The drug is delivered into the epidermis via microneedles, which do not disrupt nerve endings. This review discusses recent advances in the development of microneedles for the benefit of young scientists and to promote research in the field.Microneedles are made with a microelectromechanical system that includes silicon, metals, polymers, or polysaccharides. To pierce the superficial skin layer, solid coated microneedles can be used, followed by drug delivery. Advances in microneedle research have resulted in the development of dissolvable/degradable and hollow microneedles capable of delivering drugs at higher doses and engineering drug release. When used in conjunction with hollow microneedles, iontophoresis, sonophoresis, and electrophoresis can be used to modify drug delivery. Microneedles can deliver macromolecules like insulin, growth hormones, immunobiological, proteins, and peptides.

Deacetylepoxyazadiradione ameliorates diabesity in in-vivo zebrafish larval model by influencing the level of regulatory adipokines and oxidative stress

Obesity and diabetes constitute significant global health issues associated with one another. In contrast to diabetes, which is characterised by oxidative stress that enhances cellular damage and the following complications. Obesity dynamics involve chronic inflammation that promotes insulin resistance and metabolic disruptions. Anti-inflammatory and antioxidant agents, therefore, hold promise for synergistic effects, addressing inflammation and oxidative stress, key factors in managing obesity and diabetes. These agents can be utilized in novel drug delivery approaches. The complex interactions between deacetylepoxyazadiradione (DEA) and zebrafish larva subjected to metabolic impairment due to a high-fat diet (HFD) are examined in this study. The survival assay showed a significantly lower rate (79% survival rate) in the larvae exposed to HFD. Contrastingly, DEA treatment showed significant results with survival rates increasing dose-dependently (84%, 89%, and 94% at concentrations of 50 μM, 100 μM, and 150 μM, respectively). Further investigations revealed that DEA could reduce hyperlipidemic and hyperglycemic conditions in zebrafish larvae. Glucose levels significantly dropped in the DEA treatment, which was associated with a decline in larval weight, lipid accumulation, oxidative stress and apoptosis. Enzyme assays revealed higher antioxidant enzyme concentrations in DEA treated in-vivo larval models, which were associated with reduced expression of pro-inflammatory genes. In conclusion, the results demonstrate that DEA can alleviate oxidative stress and inflammation, effectively easing the diabesity-like state in zebrafish larvae. This offers potential avenues for developing DEA as a valuable drug candidate to manage the intricate diabesity condition.

Macrophage-Based Microrobots for Anticancer Therapy: Recent Progress and Future Perspectives.

Macrophages, which are part of the mononuclear phagocytic system, possess sensory receptors that enable them to target cancer cells. In addition, they are able to engulf large amounts of particles through phagocytosis, suggesting a potential "Trojan horse" drug delivery approach to tumors by facilitating the engulfment of drug-hidden particles by macrophages. Recent research has focused on the development of macrophage-based microrobots for anticancer therapy, showing promising results and potential for clinical applications. In this review, we summarize the recent development of macrophage-based microrobot research for anticancer therapy. First, we discuss the types of macrophage cells used in the development of these microrobots, the common payloads they carry, and various targeting strategies utilized to guide the microrobots to cancer sites, such as biological, chemical, acoustic, and magnetic actuations. Subsequently, we analyze the applications of these microrobots in different cancer treatment modalities, including photothermal therapy, chemotherapy, immunotherapy, and various synergistic combination therapies. Finally, we present future outlooks for the development of macrophage-based microrobots.

An industrial procedure for the intestinal permeability enhancement of acyclovir: in-vitro and histological evidence

Acyclovir, an antiviral drug, has low bioavailability due to its low permeability. Consequently, high drug doses and frequent administration are required. This study investigates the use of span 60, at different concentrations, as a granulating agent to enhance drug permeability using an industrial procedure on a pilot scale. The micromeritics, drug content, drug crystallinity, drug partition coefficient, and drug release of the produced formulations were examined. The findings revealed an enhanced drug partition coefficient, suggesting drug entrapment in the polar portion of span 60. The drug release profiles exhibited rapid and complete drug release. The improvement of the drug permeability was evaluated using a modified non-everted sac technique. Notably, drug permeability through the rabbit intestine significantly improved, as evidenced by various calculated permeation parameters, providing insights into the drug absorption mechanism. The widening of the paracellular pathway was observed through histological examination of the rabbit intestinal segment, which aligns with the drug absorption mechanism. The utilization of a paracellular pathway enhancer as a granulating agent holds promise as a strategy to enhance the oral bioavailability of class III drugs. Overall, this study presents a novel drug delivery approach to enhance drug permeation and bioavailability, with potential implications for other medications.

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.

Electrospun nanofibers: Exploring process parameters, polymer selection, and recent applications in pharmaceuticals and drug delivery

Electrospinning is acknowledged as a versatile technique for producing polymer nanofibers. Various methods, such as template synthesis, self-assembly, phase separation, and drawing, have been employed to create nanofibers. However, due to its simplicity, adaptability, and the inherently high surface area-to-volume ratio in electrospun fibers, electrospinning has emerged as the most suitable method for nanofiber fabrication. This review delves into the mechanisms of nanofiber techniques and establishes how electrospinning overcomes the challenges presented by other nanofabrication methods. The review explores the principles of electrospinning, processing parameters, and their effects on resulting fibers. It also discusses the properties and selection of polymers used in electrospinning, highlighting various polymer types commonly employed in pharmaceutical applications. Additionally, the review covers different types of electrospinning and their configurations, discussing their impact on drug release profiles, along with their respective advantages and disadvantages. The recent applications of electrospinning in enhancing pharmaceutical outcomes are examined, addressing crucial aspects in the pharmaceutical field, such as improving dissolution rates, masking undesirable tastes, and enabling drug delivery through various systems. In summary, this article provides a comprehensive understanding of electrospinning and its pivotal role in advancing drug delivery approaches.

FLUID PROPERTIES OF COMPONENTS FOR DEVELOPMENT OF EUDRAGIT RS-BASED IN SITU-FORMING GEL AND MICROPARTICLE AND THEIR PHASE INVERSIONS

Solvent exchange-induced in situ-forming gel (isg) and in situ-forming microparticles (ism) have been currently applied as drug delivery approaches for periodontitis treatment. Doxycycline hyclate-loaded Eudragit RS-based isg and ism were prepared in this study. The basic properties such as density, pH, surface/interfacial tension of their solvents including dimethyl sulfoxide (DMSO), N-methyl pyrrolidone (NMP), and 2-pyrrolidone (PYR) in Eudragit RS solution and oils (olive oil and camellia oil) were assessed. This research also tested for apparent viscosity of solvent and drug-free and doxycycline hyclate-loaded ERS-based isg and ism, and their phase transformation rates. Density of PYR was higher than that of DMSO whereas these solvents exhibited the less wettability than oils on glass slide. All fabricated doxycycline hyclate-loaded Eudragit RS-based ism formulations showed good emulsion physical stability with no phase separation for 1 hour. The apparent viscosity of ism was significantly less than that of isg. DMSO-based isg and ism exhibited a significantly less viscosity than that of PYR-based formulations. Rapid phase inversion was evident after isg and ism exposure to agarose gel indicating fast solvent exchange. The loose barrier of camellia oil from its less viscosity facilitated a water diffusion inward Eudragit RS-based ism easier than using viscous olive oil. Solvent exchange-induced doxycycline hyclate-loaded Eudragit RS-based ism using DMSO as the solvent and camellia oil as the continuous phase exhibited various appropriate physicochemical characteristics for applying as drug delivery system for periodontitis treatment.

Abstract 13842: A Macromolecule-Linked Prodrug of Rapamycin Shows Potent Growth Inhibitory Effects Against Activated Fibroblasts Mimicking Fibroproliferative Transformation in Pulmonary Hypertension

Introduction: Pulmonary hypertension (PH) is a life-threatening disease characterized by a progressive loss of vascular cell homeostasis with an irreversible shift toward the activated proliferative phenotype. New drug delivery approaches with improved efficacy are urgently needed for better clinical management of the disease. The present studies evaluated a novel prodrug-based strategy designed to durably suppress PH through enhanced delivery of rapamycin. We hypothesized that a long-circulating rapamycin prodrug constructed with a bioeliminable polyethylene glycol (PEG) scaffold would show efficacy as a new anti-PH drug candidate in cell culture and animal model studies. Methods: A new carrier-linked prodrug was synthesized by reversibly attaching rapamycin to 4-arm PEG (PEG-[RAPA] 4 , Mn = 40 kDa). Cell growth inhibitory effects of the construct were studied in vitro with proliferative fetal lung fibroblasts (HEL299) and transformed fibroblast-type cells (SK-LMS1), and in vivo using SK-LMS1 xenografts established in athymic nude mice. The results were analyzed by comparing the growth curve slopes (one-way ANOVA with the Tukey post hoc test). Results: Rapamycin (1-5 μM) potently inhibited proliferation of both fetal and transformed fibroblasts (75-95% inhibition 7 days post-treatment) in PDGF-BB-stimulated growth conditions (40 ng/ml, 2% FBS). Serum-stimulated (10% FBS) growth of both cell lines was also suppressed with remarkable potency at all tested concentrations (≥50% and ≥65% inhibition for HEL299 and SK-LMS1, respectively). In animal model studies, PEG-[RAPA] 4 given 2х/week strongly mitigated disease progression throughout the 4-week treatment period, whereas all animals in ‘no treatment’ and ‘blank PEG’ control groups were eliminated after reaching the end point. Statistical analysis confirmed markedly delayed growth of SK-LMS1 xenografts in the prodrug group (p = 0.032). Conclusions: Polymeric carrier-linked prodrug delivery of rapamycin effectively inhibits growth of activated fibroblasts in vitro and in a preclinical model recapitulating the altered vascular cell phenotype and proliferative character of the human disease. PEG-[RAPA] 4 is a promising candidate for further evaluation as a potential therapy for PH.

Adventitial delivery of miR-145 to treat intimal hyperplasia post vascular injuries through injectable and in-situ self-assembling peptide hydrogels

Intimal hyperplasia is a common lesion that can be observed in diverse vascular diseases. Drug-eluting stents and drug-coated balloons, which can release anti-proliferative agents to inhibit smooth muscle cell (SMC) proliferation, are developed to prevent intimal hyperplasia. However, these intervention devices still cannot achieve satisfactory clinical outcomes. In contrast to endovascular drug delivery, vascular adventitial drug delivery is a new strategy. To develop a vascular adventitial drug delivery system to treat intimal hyperplasia post vascular injuries, we loaded miR-145-5p-agomir (miR-145) into an injectable and in-situ self-assembling RAD peptide hydrogel. In vitro data showed that the miR-145 could be well incorporated into the RAD peptide hydrogels and released in a slow and controlled manner. The released miR-145 could transfect SMCs successfully, and the transfected SMCs exhibited a reduced migration capacity and higher expressions of SMC contractile biomarkers as compared to the non-transfected SMCs. In vivo data showed that the retention of the miR-145 was greatly elongated by the RAD peptide hydrogels. In addition, the application of the miR-145-loaded RAD peptide hydrogels surrounding injured arteries decreased the proliferative SMCs, promoted the regeneration of endothelium, reduced the macrophage infiltration, inhibited the neointimal formation and prevented adverse ECM remodeling via downregulation of KLF4 expression. The RAD peptide hydrogels loaded with miR-145 can successfully inhibit intimal hyperplasia after vascular injuries and thus hold great potential as an innovative extravascular drug delivery approach to treat vascular diseases. Statement of significanceIntimal hyperplasia is a common lesion that can be observed in diverse vascular diseases. Drug-eluting stents and drug-coated balloons, which can release anti-proliferative agents to inhibit smooth muscle cell (SMC) proliferation, are developed to prevent intimal hyperplasia. However, these intervention devices still cannot achieve satisfactory clinical outcomes. In contrast to endovascular drug delivery, vascular adventitial drug delivery is a new strategy. Our work here demonstrates that the RAD peptide hydrogels loaded with miR-145-5p-agomir (miR-145) can successfully reverse intimal hyperplasia after vascular injuries and thus hold great potential as an innovative vascular adventitial drug delivery approach to treat vascular diseases. Our work proposes a possible paradigm shift from endovascular drug delivery to extravascular drug delivery for vascular disorder treatment.

Investigation of Luliconazole-Loaded Mucoadhesive Electrospun Nanofibers for Anticandidal Activity in the Management of Vaginal Candidiasis.

In this study, we fabricated and evaluated luliconazole-loaded electrospun nanofibers for anticandidal activity in the management of vaginal candidiasis. Polycaprolactone (PCL)/gelatin nanofibers were designed by the electrospinning technique, and the Box-Behnken design (BBD) was adopted for optimization to get tailored fibers. The luliconazole (LCZ) drug was mixed into different concentrations (2.5, 5, 7.5, and 10%) of tea tree oil (TT oil) and loaded into the PCL/gelatin nanofibrous mats. The effective anticandidal potential of nanofiber samples were analyzed by the disk-diffusion method. Scanning electron microscopy (SEM), Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), XRD analysis, and in silico study were performed. The entrapment efficiency, swelling degree, mechanical strength, contact angle, mucoadhesion, drug release, and permeation study were assessed. The average diameter of the PCL/gelatin-optimized nanofiber was 153 nm. SEM reflected that the fabricated nanofibers were uniform and bead-free. FTIR and DSC analyzed the interaction and physical entrapment of the drug in the polymeric fibers. The entrapment efficiency of the drug-loaded nanofiber was found to be 89.2 ± 0.8%. Maximum swelling percentages at 4 h were 40.8, 18.9, and 14.0% and contact angles were 46.5°, 62.95°, and 65.78° for the blank, TT oil-loaded, and drug-loaded nanofiber, respectively, which indicated the hydrophilic nature of the fibers. The drug-loaded nanofiber had a high tensile strength with satisfactory mucoadhesive property that led to its adhesion to the vaginal mucosa with no tear. The drug-loaded nanofiber had a cumulative drug release of 67.7 ± 3.4% in 48 h, and the 12.8 ± 0.53 mm of zone of inhibition (ZOI) in 48 h illustrated an effective anticandidal activity. The TT oil-loaded nanofiber also exhibited a small ZOI of 4.3 ± 0.30 mm, indicating a synergistic effect to the antifungal activity of the drug-loaded nanofiber. LCZ-loaded nanofibers can emerge as a novel approach for vaginal drug delivery in the treatment of candida infection. Thus, this pharmaceutical investigation can help in formulating preclinical and clinical models.

Aceclofenac loaded microspheres: Formulation and evaluation of novel preprogrammed drug delivery for the treatment of arthritis

Arthritis is a widespread joint disorder globally, the patient completely dependent on NSAIDs which are administered after a fixed interval to subside the pain. This work aims to establish a preprogrammed drug delivery system of aceclofenac with a predetermined lag time for the treatment of arthritis. This new preprogrammed formulation microsphere reduces the time-dependent dose administration as it steadily releases the drug in the blood circulation reducing side effects and increasing patient compliance. Aceclofenac (ACF) loaded polymer microspheres were prepared by a new emulsification and crosslinking method using glutaraldehyde as cross-linking agent. Microspheres were prepared in 6 batches using different polymers like sodium alginate, guar gum and chitosan, alone, as well as in combinations. The type and quantity of polymers were changed in every batch while the amount of aceclofenac was unvarying. The microspheres were then evaluated for the particle size, drug content, percentage yield, percentage entrapment efficiency and percentage drug release followed by noting the lag time. The microsphere loaded with aceclofenac were formulated and evaluated, the result showed that all the preparations showed a good lag time (2–3 ​h), but chitosan (alone) gave the highest lag time, which fulfills the aim of pre-programmed drug delivery system. Preprogrammed drug release has been achieved from the microspheres over a period of 0–7 ​h, consistent with the demand for chronotherapeutic drug delivery for the treatment of arthritis. The major signification of the preparation technique includes short processing time and the lack of exposure of the ingredients to high temperatures. Aceclofenac-loaded microspheres offer a promising avenue for arthritis treatment, ensuring sustained drug release. Their potential clinical implications include enhanced therapeutic efficacy, reduced side effects, and improved patient compliance. Future directions may involve personalized formulations, targeted delivery systems, and exploring applications beyond arthritis, expanding the scope of this innovative drug delivery approach.

Advancements in Macrophage-Targeted Drug Delivery for Effective Disease Management.

Macrophages play a crucial role in tissue homeostasis and the innate immune system. They perform essential functions such as presenting antigens, regulating cytokines, and responding to inflammation. However, in diseases like cancer, cardiovascular disorders, and autoimmune conditions, macrophages undergo aberrant polarization, which disrupts tissue regulation and impairs their normal behavior. To address these challenges, there has been growing interest in developing customized targeted drug delivery systems specifically designed for macrophage-related functions in different anatomical locations. Nanomedicine, utilizing nanoscale drug systems, offers numerous advantages including improved stability, enhanced pharmacokinetics, controlled release kinetics, and precise temporal drug delivery. These advantages hold significant promise in achieving heightened therapeutic efficacy, specificity, and reduced side effects in drug delivery and treatment approaches. This review aims to explore the roles of macrophages in major diseases and present an overview of current strategies employed in targeted drug delivery to macrophages. Additionally, this article critically evaluates the design of macrophage-targeted delivery systems, highlighting limitations and discussing prospects in this rapidly evolving field. By assessing the strengths and weaknesses of existing approaches, we can identify areas for improvement and refinement in macrophage-targeted drug delivery.