Carrier-based Delivery Systems Research Articles

Carrier-based delivery system of phytohormones in plants: stepping outside of the ordinary.

Climate change is increasing the stresses on crops, resulting in reduced productivity and further augmenting global food security issues. The dynamic climatic conditions are a severe threat to the sustainability of the ecosystems. The role of technology in enhancing agricultural produce with the minimum environmental impact is hence crucial. Active molecule/Plant growth regulators (PGRs) are molecules helping plants' growth, development, and tolerance to abiotic and biotic stresses. However, their degradation, leaching in surrounding soil and ground water, as well as the assessment of the correct dose of application etc., are some of the technical disadvantages faced. They can be resolved by encapsulation/loading of PGRs on polymer matrices. Micro/nanoencapsulation is a revolutionary tool to deliver bioactive compounds in an economically affordable and environmentally friendly way. Carrier-based smart delivery systems could be a better alternative to PGRs application in the agriculture field than conventional methods (e.g., spraying). The physiochemical properties and release kinetics of PGRs from the encapsulating system are being explored. Therefore, the present review emphasizes the current status of PGRs encapsulation approach and their potential benefits to plants. This review also addressed the mechanistic action of carrier-based delivery systems for release, which may aid in developing smart delivery systems with specific tailored properties in future research.

Statistical simplex centroid experimental design for evaluation of pectin, modified chitosan and modified starch as encapsulating agents on the development of vitamin E-loaded microparticles by spray-drying

Vitamin E encapsulation into biopolymer-based microparticles, obtained by spray-drying technology, was proposed to improve the encapsulation efficiency and the controlled release of fat-soluble vitamin. Binary and ternary blends of pectin, modified chitosan and modified starch, modified starch + modified chitosan, modified starch + pectin, modified chitosan + pectin and modified starch + modified chitosan + pectin ((0.33, 0.33, 0.33), (0.70, 0.15, 0.15), (0.15, 0.70, 0.15) and (0.15, 0.15, 0.70)) were proposed to produce and evaluate different carrier-based delivery systems. Vitamin E-loaded microparticles and empty microparticles were created with a product yield between 9 and 49 %. The mean diameter among all microparticles varied between 3.74 ± 0.02 and 421 ± 21 μm (differential volume distribution). Oval, spherical or irregular microparticles, with a variable morphology from a smooth to a high rough surface structure, with concavities, were produced. All vitamin E-loaded microparticles exhibited an encapsulation efficiency higher than 70 %. The slower vitamin E controlled release was observed from microparticles composed by modified chitosan (>36 h), while the faster release was achieved from microparticles individually composed by pectin (39 min). In general, the Fickian diffusion is the main release mechanism involved in the microparticles produced with modified chitosan, other formulations combine also other mechanisms such as swelling.

In vitro bioaccessibility and intestinal transport of retinoic acid in ethyl cellulose-based microparticles and impact of meal co-ingestion

The development of carrier-based delivery systems for oral administration of retinoic acid (RA), that provides its release and absorption at intestinal level, is of major relevance in the treatment of acute promyelocytic leukemia. The aim of this work was to evaluate RA bioaccessibility and intestinal transport on ethyl cellulose (EC)- and EC + polyethylene glycol (ECP)-based microparticles and to understand the impact of meal co-ingestion by applying in vitro assays. RA-loaded microparticles were produced by spray-drying with an encapsulation efficiency higher than 90 % for both formulations. The gastric bioaccessibility of RA (after in vitro static digestion of RA-loaded particles) was lower than 3 % for both types of microparticles, with and without meal co-ingestion. Whereas after intestinal digestion, RA bioaccessibility was significantly higher and affected by the type of microparticles and the presence of meal. The digestion of EC- and ECP-based microparticles without diet enabled a significantly higher bioaccessibility of RA when compared to the one recorded for the co-digestion of these microparticles with diet. Herein, RA bioaccessibility decreased from 84 ± 1 to 24 ± 6 % (p < 0.0001) for microparticles EC and 54 ± 4 to 25 ± 5 % (p < 0.001) for microparticles ECP. Moreover, comparing both types of microparticles, RA bioaccessibility was significantly higher for EC-based microparticles digested without diet (p < 0.0001). At last, the bioaccessibility of RA was similar among EC- and ECP-based microparticles when co-digested with diet. Intestinal transport experiments performed in Caco-2 monolayers evidenced that after 2 h of transport the amount of RA retained in the apical compartment was higher than the amount that reached the basolateral compartment evidencing a slow transport at intestinal level that was higher when RA is spiked in the blank of digestion and the meal digestion samples compared to RA dissolved in HBSS (44 ± 6 (p < 0.01) and 38 ± 1 (p < 0.05) vs 26 ± 2 %, respectively).

Exploring the therapeutic potential of recombinant human lysozyme: a review on wound management system with antibacterial.

Lysozyme, a natural antibacterial enzyme protein, possesses the ability to dissolve the cell walls of Gram-positive bacteria, demonstrating broad-spectrum antibacterial activity. Despite its significant potential in treating wound infections and promoting wound healing, its widespread clinical application has yet to be realized. Current research is primarily focused on carrier-based delivery systems for lysozyme. In this review, we discuss four delivery systems that can be employed for lysozyme in wound healing treatment, specifically hydrogels, nanofilms, electrospun fibrous membranes, and modified-lysozyme composite systems. These systems not only enhance the stability of lysozyme but also enable its controlled and sustained release at wound sites, potentially overcoming some of the challenges associated with its direct application. Lastly, we delve into the perspectives and challenges related to the use of these delivery systems, hoping to spur further research and innovation in this promising field.

Design and Development of a Topical Nanogel Formulation Comprising of a Unani Medicinal Agent for the Management of Pain.

The oil of the Unani medicinal herb Baboona (Matricaria chamomilla) has shown potential in the management of pain. However, predicaments such as poor skin penetration, skin sensitization, liable to degradation, and volatile nature restrict its use. Therefore, our group for the first time has developed a carrier-based delivery system to facilitate the direct application of chamomile oil to the forehead. The developed nanogel was characterized for physical parameters such as compatibility, TEM, and stability studies. Further, it was also evaluated for pH, viscosity, spread ability, and extrudability, as well as through texture analyses, in vitro studies, and skin irritation tests. The formulation was successfully developed with all the necessary attributes. The in vitro studies revealed the enhanced skin penetration of chamomile oil nanogel. The in vivo studies were also performed in chemically induced pain models, mimicking migraine. The studies show significant improvement of the pain threshold for chamomile nanogel when compared to the positive control group and the results were comparable to marketed diclofenac formulations. Finally, the encapsulation into nanogel reduced the skin irritation property. The nanogel formulation showed promising effects in the pain management of migraine.

Pharmaceutical/Clinical Strategies in the Treatment of Acute Promyelocytic Leukemia: All-Trans Retinoic Acid Encapsulation by Spray-Drying Technology as an Innovative Approach-Comprehensive Overview.

Acute promyelocytic leukemia (APL) is phenotypically characterized by the accumulation of dysplastic promyelocytes, resulting from a cytogenetic condition due to the balanced chromosomal translocation t(15;17)(q22;q21). Current first-line treatment of APL includes all-trans retinoic acid (all-trans RA), with or without arsenic trioxide, combined with chemotherapy, and a chemotherapy-free approach wherein arsenic trioxide is used alone or in combination with all-trans RA. The usage of all-trans RA revolutionized the treatment of APL, with survival rates of 80 to 90% being achieved. The mechanism of action of all-trans RA is based on regulation of gene transcription, promoting the differentiation of leukemic promyelocytes. Encapsulation technology has been explored as an innovative strategy to overcome the major drawbacks related to the all-trans RA oral administration in the APL treatment. The most recently published works on this subject highlight the development and optimization of carrier-based delivery systems based in microparticle formulations obtained by spray-drying to be used in the treatment of APL. The ultimate goal is to obtain a controlled delivery system for RA oral administration capable of providing a slow release of this bioactive compound in the intestinal lumen.

Poloxamer-linked prodrug of a topoisomerase I inhibitor SN22 shows efficacy in models of high-risk neuroblastoma with primary and acquired chemoresistance.

High‐risk solid tumors continue to pose a tremendous therapeutic challenge due to multidrug resistance. Biological mechanisms driving chemoresistance in high‐risk primary and recurrent disease are distinct: in newly diagnosed patients, non‐response to therapy is often associated with a higher level of tumor “stemness” paralleled by overexpression of the ABCG2 drug efflux pump, whereas in tumors relapsing after non‐curative therapy, poor drug sensitivity is most commonly linked to the dysfunction of the tumor suppressor protein, p53. In this study, we used preclinical models of aggressive neuroblastoma featuring these characteristic mechanisms of primary and acquired drug resistance to experimentally evaluate a macromolecular prodrug of a structurally enhanced camptothecin analog, SN22, resisting ABCG2‐mediated export, and glucuronidation. Together with extended tumor exposure to therapeutically effective drug levels via reversible conjugation to Pluronic F‐108 (PF108), these features translated into rapid tumor regression and long‐term survival in models of both ABCG2‐overexpressing and p53‐mutant high‐risk neuroblastomas, in contrast to a marginal effect of the clinically used camptothecin derivative, irinotecan. Our results demonstrate that pharmacophore enhancement, increased tumor uptake, and optimally stable carrier‐drug association integrated into the design of the hydrolytically activatable PF108‐[SN22]2 have the potential to effectively combat multiple mechanisms governing chemoresistance in newly diagnosed (chemo‐naïve) and recurrent forms of aggressive malignancies. As a macromolecular carrier‐based delivery system exhibiting remarkable efficacy against two particularly challenging forms of high‐risk neuroblastoma, PF108‐[SN22]2 can pave the way to a robust and clinically viable therapeutic strategy urgently needed for patients with multidrug‐resistant disease presently lacking effective treatment options.

25154 Enhanced topical delivery of salicylic acid from an encapsulated system

Salicylic acid is a beta hydroxy acid that is clinically proven in the prevention and treatment of acne by encouraging skin exfoliation and unclogging of pores. Despite its bioactivity, the low water solubility of salicylic acid makes it challenging to formulate, and also limits its permeation into skin when applied topically. Various carrier-based delivery systems have been developed in recent years targeting either enhanced penetration for better efficacy, or controlled release for less side effect and long-lasting benefit. Among them, the multilamellar vesicle (MLV) delivery system encapsulates active ingredients in its onion-like structure; the individual “layers” peel off over time to provide deep and sustained active release. In this study, we compared the skin penetration of 2% salicylic acid from a topical gel with and without a specific MLV delivery system. Human skin explants were treated with the gel formulations for 24 hours in triplicates on a Franz diffusion cell setup. ATR-FTIR imaging was conducted on skin cross sections after the treatment. Unique spectrospopic signals (eg, 850 cm-1) were identified to monitor salicylic acid. The hyperspectral images revealed that a deeper and overall greater level (2-fold) of salicylic acid was delivered into skin through MLV encapsulation as compared with the control formula, which contains an equal amount of salicylic acid in free form. This proves that the MLV is an effective vehicle for topical delivery of salicylic acid.

Nano-Medicines a Hope for Chagas Disease!

Chagas disease, is a vector-mediated tropical disease whose causative agent is a parasitic protozoan named Trypanosoma cruzi. It is a very severe health issue in South America and Mexico infecting millions of people every year. Protozoan T. cruzi gets transmitted to human through Triatominae, a subfamily of the Reduviidae, and do not have any effective treatment or preventative available. The lack of economic gains from this tropical parasitic infection, has always been the reason behind its negligence by researchers and drug manufacturers for many decades. Hence there is an enormous requirement for more efficient and novel strategies to reduce the fatality associated with these diseases. Even, available diagnosis protocols are outdated and inefficient and there is an urgent need for rapid high throughput diagnostics as well as management protocol. The current advancement of nanotechnology in the field of healthcare has generated hope for better management of many tropical diseases including Chagas disease. Nanoparticulate systems for drug delivery like poloxamer coated nanosuspension of benzimidazole have shown promising results in reducing toxicity, elevating efficacy and bioavailability of the active compound against the pathogen, by prolonging release, thereby increasing the therapeutic index. Moreover, nanoparticle-based drug delivery has shown promising results in inducing the host’s immune response against the pathogen with very few side effects. Besides, advances in diagnostic assays, such as nanosensors, aided in the accurate detection of the parasite. In this review, we provide an insight into the life cycle stages of the pathogen in both vertebrate host and the insect vector, along with an overview of the current therapy for Chagas disease and its limitations; nano carrier-based delivery systems for antichagasic agents, we also address the advancement of nano vaccines and nano-diagnostic techniques, for treatment of Chagas disease, majorly focusing on the novel perspectives in combating the disease.

Polysaccharide-based delivery systems for curcumin and turmeric powder encapsulation using a spray-drying process

Curcumin is a hydrophobic polyphenol with a large spectrum of pharmacological functions, such as anti-inflammatory, anticarcinogenic and antioxidant, among others. Due to its chemical instability, the incorporation of curcumin into carrier-based delivery systems has been proposed to improve its stabilization and bioavailability in the human body. The present work suggests the spray-drying technique for the encapsulation of curcumin and turmeric powder (with the active compound curcumin) using the polysaccharides pectin, maltodextrin, inulin and xanthan as encapsulating agents. A product yield between 7.52 and 60.60% was registered for all the microparticles produced: empty, loaded with turmeric powder and loaded with curcumin. Microparticles with a spherical form, rough surface (pectin, maltodextrin and xanthan microparticles) and smooth surface (inulin microparticles) were produced. The fastest core compound release from curcumin- and turmeric powder-loaded microparticles was registered with inulin and maltodextrin, respectively. The most appropriate kinetic model to describe the registered release profiles is the Weibull model.

In vitro remineralization of enamel white spot lesions with a carrier-based amorphous calcium phosphate delivery system.

To achieve in vitro remineralization of enamel white spot lesions (WSLs) via a mesoporous delivery system of amorphous calcium phosphate (ACP) precursors. Amine-functionalized expanded pore mesoporous silica (aMSN) was loaded with polyacrylic acid-stabilized amorphous calcium phosphate (PAA-ACP) to develop a carrier-based delivery system (PAA-ACP@aMSN). Thirty-six artificial WSLs samples were created and randomly assigned to three treatments: artificial saliva solution (negative control, n = 12), casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) slurry (n = 12), and PAA-ACP@aMSN slurry (n = 12). Surface microhardness, Raman intensity, and color were measured before/after artificial demineralization and after remineralization treatments to evaluate the remineralization level of each sample. SEM images were taken on the surface and cross-section of samples to observe microstructure changes. The surface microhardness recovery ratio (%SMHRR), Raman intensity change ratio (%ICR), and color recovery ratio (%CRR) were not significantly different between CPP-ACP and PAA-ACP@aMSN groups (P > 0.05), but both of them had significantly higher %SMHRR, %ICR, and %CRR values than negative control (P < 0.01). SEM images showed that apparent enamel prism imprints and inter-prism gaps in negative control were masked by mineral deposition in the PAA-ACP@aMSN and CPP-ACP groups. PAA-ACP@aMSN has an ability to remineralize enamel WSLs. The carrier-based amorphous calcium phosphate delivery system has great potential to serve as a remineralizing agent for the treatment of WSLs.

Characterization of biopolymer-based systems obtained by spray-drying for retinoic acid controlled delivery

Novel carrier-based delivery systems have been strategically designed and developed to beneficiate retinoic acid (RA) as medical agent. The final purpose is to deal with the factors which hamper RA efficacy (e.g. short half-life, low absorption in the intestine and severe side effects). The present work proposes the inclusion of RA into arabic gum, modified chitosan and alginic acid sodium microcapsules using spray-drying technology. The product yield varied between 26 and 38% for empty and RA-loaded microcapsules. Spherical microcapsules with a rough, slightly rough and smooth surface (according to the encapsulating agent) and with an average size in the range of 3.279 to 10.880 μm were obtained. Controlled release studies evidenced the fastest RA release (in 99 min) for the modified chitosan formulation, while alginic acid sodium microcapsules enabled a RA release for >7 h. The main kinetic release models, based on different mathematical functions, were applied to RA. The Weibull model revealed to be the most appropriate to characterize the RA release profiles.

Translation of a solution-based biomineralization concept into a carrier-based delivery system via the use of expanded-pore mesoporous silica

Mineralization of collagen fibrils using solution-based systems containing biomimetic analogs of matrix proteins to stabilize supersaturated calcium phosphate solutions have been predictably achieved in vitro. Solution-based systems have limitations when used for in-situ remineralization of human hypomineralized tissues because periodic replenishment of the mineralizing solution is infeasible. A carrier-based platform designed for delivering mineral precursors would be highly desirable. In the present work, mesoporous silica nanoparticles with expanded pores (eMSN; 14.8nm) were synthesized. Polyacrylic acid–stabilized amorphous calcium phosphate (PA–ACP) was generated from a supersaturated calcium and phosphate ion-containing solution, and chosen as the model mineralizing phase. After amine functionalization (AF) of the eMSN through a post-grafting method, the positively-charged AF-eMSN enabled loading of PA–ACP by electrostatic interaction. In-vitro cytotoxicity testing indicated that PA–ACP@AF-eMSN was highly biocompatible. The release kinetics of mineralization precursors from PA–ACP@AF-eMSN was characterized by an initial period of rapid calcium and phosphate release that reached a plateau after 120h. Intrafibrillar mineralization was examined using a 2-D fibrillar collagen model; successful mineralization was confirmed using transmission electron microscopy. To date, this is the first endeavor that employs expanded-pore mesoporous silica to deliver polymer-stabilized intermediate precursors of calcium phosphate for intrafibrillar mineralization of collagen. The carrier-based delivery system bridges the gap between contemporary solution-based biomineralization concepts and clinical practice, and is useful for in-situ remineralization of bone and teeth. Statement of significanceConcepts of collagen biomineralization have been reasonably well established in the past few years and intrafibrillar mineralization of collagen fibrils can be predictably achieved with analogs of matrix proteins using solution-based systems. However, solution-based systems have their limitations in clinical applications that require direct application of mineralization precursors in-situ because periodic replenishment of the mineralizing solution is impossible. The present work presents for the first time, the use of amine-functionalized mesoporous silica with expanded pores for loading and release of polyacid-stabilized amorphous calcium phosphate mineralization precursors, and for intrafibrillar mineralization of type I collagen fibrils. This strategy represents an important step in the translational application of contemporary biomineralization concepts for in-situ remineralization of bone and teeth.

Carrier-based drug delivery system for treatment of acne.

Approximately 95% of the population suffers at some point in their lifetime from acne vulgaris. Acne is a multifactorial disease of the pilosebaceous unit. This inflammatory skin disorder is most common in adolescents but also affects neonates, prepubescent children, and adults. Topical conventional systems are associated with various side effects. Novel drug delivery systems have been used to reduce the side effect of drugs commonly used in the topical treatment of acne. Topical treatment of acne with active pharmaceutical ingredients (API) makes direct contact with the target site before entering the systemic circulation which reduces the systemic side effect of the parenteral or oral administration of drug. The objective of the present review is to discuss the conventional delivery systems available for acne, their drawbacks, and limitations. The advantages, disadvantages, and outcome of using various carrier-based delivery systems like liposomes, niosomes, solid lipid nanoparticles, and so forth, are explained. This paper emphasizes approaches to overcome the drawbacks and limitations associated with the conventional system and the advances and application that are poised to further enhance the efficacy of topical acne formulations, offering the possibility of simplified dosing regimen that may improve treatment outcomes using novel delivery system.

Targeted Tumor Therapies at a Glance

Conventional tumor therapy is usually based on surgery, radiation and chemotherapy. Treatment with chemotherapeutics is often impeded by dose-limiting toxicities. Therefore, medical scientists sought for tools to improve chemotherapy by directly coupling targeting molecules to cytotoxic substances. This review provides a general overview on the development of targeted drugs designed for tumor therapy. Further carrier-based delivery systems of anti-tumorigenic drugs will not be described here. The targeting moiety is usually an antibody or a fragment thereof. Growth factors, cytokines and ligands are also used as targeting moiety. The targeting moiety is coupled to the toxic moiety either chemically or both components were combined as fusion proteins. In addition to those targeted molecules containing conventional chemotherapeutics, more sophisticated targeted drugs were developed containing protein toxins, such as diphtheria toxin or Pseudomonas exotoxin. Only a small number of these protein toxins inside tumor cells results in efficient killing of the target cell. Several of these targeted toxins are currently in clinical trials. Another targeting mechanism utilizes the activation of formerly harmless substances in the vicinity of tumor cells. This mechanism is referred to as directed enzyme prodrug therapy.

Polymer electrolyte membrane for electrochemical applications

Mineralization of collagen fibrils using solution-based systems containing biomimetic analogs of matrix proteins to stabilize supersaturated calcium phosphate solutions have been predictably achieved in vitro. Solution-based systems have limitations when used for in-situ remineralization of human hypomineralized tissues because periodic replenishment of the mineralizing solution is infeasible. A carrier-based platform designed for delivering mineral precursors would be highly desirable. In the present work, mesoporous silica nanoparticles with expanded pores (eMSN; 14.8 nm) were synthesized. Polyacrylic acid–stabilized amorphous calcium phosphate (PA–ACP) was generated from a supersaturated calcium and phosphate ion-containing solution, and chosen as the model mineralizing phase. After amine functionalization (AF) of the eMSN through a post-grafting method, the positively-charged AF-eMSN enabled loading of PA–ACP by electrostatic interaction. In-vitro cytotoxicity testing indicated that PA–[email protected] was highly biocompatible. The release kinetics of mineralization precursors from PA–[email protected] was characterized by an initial period of rapid calcium and phosphate release that reached a plateau after 120 h. Intrafibrillar mineralization was examined using a 2-D fibrillar collagen model; successful mineralization was confirmed using transmission electron microscopy. To date, this is the first endeavor that employs expanded-pore mesoporous silica to deliver polymer-stabilized intermediate precursors of calcium phosphate for intrafibrillar mineralization of collagen. The carrier-based delivery system bridges the gap between contemporary solution-based biomineralization concepts and clinical practice, and is useful for in-situ remineralization of bone and teeth.Concepts of collagen biomineralization have been reasonably well established in the past few years and intrafibrillar mineralization of collagen fibrils can be predictably achieved with analogs of matrix proteins using solution-based systems. However, solution-based systems have their limitations in clinical applications that require direct application of mineralization precursors in-situ because periodic replenishment of the mineralizing solution is impossible. The present work presents for the first time, the use of amine-functionalized mesoporous silica with expanded pores for loading and release of polyacid-stabilized amorphous calcium phosphate mineralization precursors, and for intrafibrillar mineralization of type I collagen fibrils. This strategy represents an important step in the translational application of contemporary biomineralization concepts for in-situ remineralization of bone and teeth.