RESUMO
In the last 20 years, protein, peptide and nucleic acid-based therapies have become the fastest growing sector in the pharmaceutical industry and play a vital role in disease therapy. However, the intrinsic sensitivity and large molecular sizes of biotherapeutics limit the available routes of administration. Currently, the main administration routes of biomacromolecules, such as parenteral, oral, pulmonary, nasal, rectal and buccal routes, each have their limitations. Several non-invasive strategies have been proposed to overcome these challenges. Researchers were particularly interested in microneedles (MNs) and polymeric films because of their less invasiveness, convenience and greater potential to preserve the bioactivity of biotherapeutics. By facilitating with MNs and polymeric films, biomacromolecules could provide significant benefits to patients suffering from various diseases such as cancer, diabetes, infectious and ocular diseases. However, before these devices can be used on patients, how to upscale MN manufacture in a cost-effective and timely manner, as well as the long-term safety of MN and polymeric film applications necessitates further investigation.
Assuntos
Sistemas de Liberação de Medicamentos , Peptídeos , Humanos , Administração Cutânea , Peptídeos/química , Peptídeos/metabolismo , Pele/metabolismoRESUMO
Coronary artery disease (CAD) is currently a leading cause of death worldwide. In the history of percutaneous coronary intervention for the treatment of CAD, a drug-eluting stent (DES) is recognized as a revolutionary technology that has the unique ability to significantly reduce restenosis and provide both mechanical and biological solutions simultaneously to the target lesion. The aim of the research work was to design and fabricate DES coated with a nanoparticulate drug formulation. Sirolimus, an inhibitor of the smooth muscle cell (SMC) proliferation and migration, was encapsulated in polymeric nanoparticles (NPs). The NP formulation was characterized for various physicochemical parameters. Cell viability and cell uptake studies were performed using human coronary artery smooth muscle cells (HCASMCs). The developed NP formulation showed enhanced efficacy compared to plain drug solution and exhibited time-dependent uptake into the HCASMCs. The developed NP formulation was coated on the Flexinnium™ ultra-thin cobalt-chromium alloy coronary stent platform. The NP-coated stents were characterized for morphology and residual solvent analysis. In vitro drug release was also evaluated. Ex vivo arterial permeation was carried out to evaluate the NP uptake from the surface of the stents. The characterization studies together corroborated that the developed NP coated stent can be a promising replacement of the current DESs.
Assuntos
Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Stents Farmacológicos , Nanopartículas , Intervenção Coronária Percutânea/métodos , Sirolimo/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Fenômenos Químicos , Ligas de Cromo , Vasos Coronários/citologia , Vasos Coronários/metabolismo , Humanos , Técnicas In Vitro , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Sirolimo/farmacocinética , Sirolimo/farmacologiaRESUMO
Pulmonary hypertension (PH) is characterized by the rise in mean pulmonary arterial pressure (≥ 20 mmHg at rest) due to the narrowing of the pulmonary arterial networks. Current treatments provide symptomatic treatment and the underlying progress of PH continues leading to higher mortality rates due to non-reversal of the disease. This warrants the need for drug therapies targeting angiogenesis and vascular remodeling mechanisms. Resveratrol, SIRT 1 activator, alters various signaling pathways, inhibits apoptosis, and negatively regulates angiogenesis either by increasing the production of anti-angiogenic factors or inhibiting pro-angiogenic factors. Our work describes the liposomal formulation development, physicochemical characterization, and in vitro aerosolization performance of resveratrol liposomal dry powder formulation. The resveratrol liposomal dry powder formulation reduces the right ventricular systolic pressure measured during right jugular vein catheterization and significantly reverses the PH disease pathological changes as demonstrated by histological observations of pulmonary arterial lumen and ventricular hypertrophy. The developed resveratrol liposomal dry powder formulation alleviates the pulmonary arterial remodeling through its antiangiogenic mechanism and indicates a promising therapeutic strategy for PH treatment.
Assuntos
Hipertensão Pulmonar , Sirtuínas , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/metabolismo , Lipossomos/uso terapêutico , Pós , Resveratrol/farmacologia , Sirtuínas/uso terapêuticoRESUMO
The aim of this research was to develop a nanosuspension of aprepitant (APT) using the Nano-by-Design approach. A novel microfluidization technology was used for processing the formulation. A 32 full factorial design was used for the optimization of dependent variables, which included critical quality attributes like particle size and polydispersity index. Subsequently, the design space was generated and the optimum formulation was located using desirability constraints followed by its validation.The prepared nanosuspension had a particle size of 721 nm ± 5%, a polydispersity index of 0.106 ± 3%, and a zeta potential of - 8.06 ± 5 mV. Its surface morphology was studied using SEM, DSC, and XRD. It revealed that the prepared nanosuspension had a nano-crystalline nature. The process parameters did not lead to any physicochemical interaction between the drug and excipients. This was confirmed using FTIR analysis. In vitro dissolution studies revealed 100% cumulative drug release over 60 min, showing better results in comparison with pure APT. Thus, it has been shown that microfluidization can be an industrially feasible, novel, green technology for the preparation of a stable APT nanosuspension for improving the dissolution profile of the drug.
Assuntos
Nanopartículas , Aprepitanto , Liberação Controlada de Fármacos , Nanopartículas/química , Tamanho da Partícula , Solubilidade , SuspensõesRESUMO
OBJECTIVE: The article focuses on exploring and comparing two top-down methods, i.e. media milling and microfluidization for the fabrication of nanocrystals of rifampicin (RIF), a poorly water-soluble drug in terms of their potential for generation of stable and efficacious nanocrystals. SIGNIFICANCE: Nanocrystals are often the system of choice for the formulation of poorly water-soluble drugs. The characteristic benefit of nanocrystals lies in their ability to boost the bioavailability of such drugs by enhancing their saturation solubility and dissolution velocity. Nanocrystals can be prepared by either bottom-up or top-down approach. The latter is often preferred due to the feasibility of scale-up and economical nature. Hence, the emphasis is on these methods. METHODS: Stable RIF nanocrystals (RIF NCs) were developed and optimized using media milling and microfluidizer method by incorporating a suitable surfactant/stabilizer. The developed nanocrystals were evaluated for their saturation solubility, in vitro dissolution, solid-state characteristics, morphology, intrinsic dissolution rate, and short-term physical stability. RESULTS: Both the methods were found to be equally efficient in terms of development of stable RIF NCs, while in terms of processing time and efficacy, microfluidization was found to be advantageous. Amorphization and polymorphic conversion were evident based on the results of solid-state characterization. Furthermore, both formulations exhibited an enhanced solubility and faster dissolution velocity. CONCLUSION: Based on the characterization outcomes, it can be concluded that both the top-down technologies could be successfully applied to develop nanocrystals of poorly water-soluble drugs. However, microfluidization was found to outplay media milling in terms of processing time and drug loading.
Assuntos
Química Farmacêutica , Nanopartículas , Disponibilidade Biológica , Tamanho da Partícula , Solubilidade , TensoativosRESUMO
The current work is focused on the development of docetaxel loaded pomegranate seed oil based lipid nanosystem. Docetaxel loaded pomegranate seed oil nanostructured lipid carriers (DTX-PSO-NLCs) were formulated by the melt emulsification method for parenteral delivery. The developed formulation was characterized in terms of their physicochemical parameters, solid-state characterization, in vitro drug release, in vitro cytotoxicity studies, and in vivo pharmacokinetics and biodistribution studies. Stability studies were carried out as per ICH guidelines Q1A. Melt emulsification method resulted in the formulation of stable DTX-PSO-NLCs with a particle size in the range of 150-180 nm and an entrapment efficiency of 63-65%. The in vitro release showed a slow and sustained release of the drug from the formulation compared to the marketed formulation (i.e., Daxotel®). The formulation was found to be stable for a period of 12 months at conditions of 4°C ± 2°C, 25°C ± 2°C/60% RH ± 5%RH, and 40°C ± 2°C/75% RH ± 5%RH. The developed nanosystem exhibited promising antitumor activity against various types of cancerous cell lines (i.e., MCF7, DU145, U87MG, and NCI-H460) relative to the marketed formulation. The pharmacokinetic evaluation revealed that DTX-PSO-NLCs had a better kinetic profile compared to the marketed formulation. Graphical abstract.
Assuntos
Antineoplásicos/administração & dosagem , Docetaxel/administração & dosagem , Lipídeos/administração & dosagem , Nanoestruturas/química , Óleos de Plantas/administração & dosagem , Punica granatum/embriologia , Sementes/química , Animais , Portadores de Fármacos/química , Tamanho da Partícula , Distribuição TecidualRESUMO
Transdermal route has been explored for various agents due to its advantage of bypassing the first pass effect and sustained release of drug. Due to strong barrier properties of the skin, mainly stratum corneum (SC), the delivery of many therapeutic agents across the skin has become challenging. Few drugs with specific physicochemical properties (molecular weight <500 Da, adequate lipophilicity, and low melting point) can be effectively administered via transdermal route. However, delivery of hydrophilic drugs and macromolecular agents including peptides, DNA and small interfering RNA is challenging. Drug penetration through the SC may involve bypass or reversible disruption of SC layer by various means. Recently, the use of micron-scale needles has been proposed in increasing skin permeability and shown to dramatically increase permeation, especially for macromolecules. Microneedles (MNs) can penetrate through the SC layer of the skin into the viable epidermis, avoiding contact with nerve fibers and blood vessels that reside primarily in the dermal layer. This review summarizes the types of MNs and fabrication techniques of different types of MNs. The safety aspects of the materials used for fabrication have been discussed in detail. Biological applications and relevant phase III clinical trials are also highlighted.
Assuntos
Administração Cutânea , Sistemas de Liberação de Medicamentos/instrumentação , Microinjeções/instrumentação , Microinjeções/métodos , Agulhas , Animais , HumanosRESUMO
Nanoparticles have specific physicochemical properties different to bulk materials of the same composition and such properties make them very attractive for commercial and medical applications. Mucoadhesive nanoparticulate dosage forms are designed to enable prolonged retention of these nanoparticles at the site of application, providing a controlled drug release for improved therapeutic outcome. Moreover, drug delivery across the mucosa bypasses the first-pass hepatic metabolism and avoids the degradation by gastrointestinal enzymes. However, like most new technologies, there is a rising debate concerning the possible transmucosal side effects resulting from the use of particles at the nano level. In fact, these nanoparticles on entering the body, deposit in several organs and may cause adverse biological reactions by modifying the physiochemical properties of living matter. Several investigators have found nanoparticles responsible for toxicity in different organs. In addition, the toxicity of nanoparticles also depends on whether they are persistent or cleared from the different organs of entry and whether the host can raise an effective response to sequester or dispose of the particles. In contrast to many efforts aimed at exploiting desirable properties of nanoparticles for medicine, there are limited attempts to evaluate potentially undesirable effects of these particles when administered intentionally for medical purposes. This chapter focuses on the overview of the mucosal systems, fate of nanoparticles, mechanism of nanoparticle's toxicity and the various toxicity issues associated with nanoparticles through mucosal routes.
Assuntos
Sistemas de Liberação de Medicamentos/efeitos adversos , Mucosa Intestinal/metabolismo , Fígado/metabolismo , Nanopartículas/efeitos adversos , Nanopartículas/metabolismo , Animais , Humanos , Mucosa Intestinal/patologia , Fígado/patologia , Especificidade de ÓrgãosRESUMO
Currently, artemisinin-based combination therapy is considered the best option in the treatment of malaria. However, toxicity of artemisinins limits their use in pregnancy. In the absence of sufficient toxicity data, the World Health Organization recommends that artemisinins are not to be used in the first trimester of pregnancy and can be used only in second and third trimesters, when other treatments are not available. We have recently observed that drugs loaded in nanolipid carriers are selectively taken up in Plasmodium-infected erythrocytes with a concomitant reduction in the dose required to cure animals. Thus, 20% of the therapeutic dose of artemether-clindamycin (ARM-CP) loaded in nanostructured lipid carriers (NLCs; mean particle size 55 ± 10 nm) resulted in complete parasite clearance and 100% survival of infected mice. Here, we investigate the teratogenicity of this formulation in rodents (dosing on alternate days from 6th day to 18th day of gestation; 12-15 animals/group). The teratogenicity of drug-free NLCs and artesunate-clindamycin (ARS-CP) solution was also evaluated. We found that the therapeutic dose of ARS-CP caused fetal resorptions (87.5% resorptions in 8 litters), suggesting its unsuitability for use in pregnancy. Artesunate-clindamycin NLCs at therapeutic doses also resulted in â¼90% fetal resorptions in 10 litters examined. However, postimplantation losses or fetal malformations were not observed at the dose of ARM-CP NLCs that was required for complete parasite clearance in preclinical trials (ie, 20% of the therapeutic dose). Our data suggest that the NLCs loaded with 20% of the therapeutic dose of ARM-CP may have potential in treating malaria during pregnancy.
Assuntos
Antimaláricos/toxicidade , Artemisininas/toxicidade , Clindamicina/toxicidade , Portadores de Fármacos/toxicidade , Malária/tratamento farmacológico , Troca Materno-Fetal , Nanoestruturas/toxicidade , Animais , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Artemeter , Artemisininas/administração & dosagem , Artemisininas/uso terapêutico , Clindamicina/administração & dosagem , Clindamicina/uso terapêutico , Diglicerídeos/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/uso terapêutico , Feminino , Masculino , Camundongos , Monoglicerídeos/química , Nanoestruturas/administração & dosagem , Nanoestruturas/uso terapêutico , Gravidez , Ratos Sprague-DawleyRESUMO
The present investigation is aimed at development and characterization of sumatriptan succinate orodispersible tablets (ODTs) prepared by freeze drying technology. The tablet excipients were screened and the composition was optimized based on parameters which involved general appearance, tablet size and shape, uniformity of weight, mechanical properties, surface pH, moisture analysis, drug content, wetting time, in vitro and in vivo disintegration time. Furthermore, fourier transform infrared spectroscopy, differential scanning calorimetry, scanning electron micrograph of cross-section of the tablet and in vitro dissolution studies were performed. Studies revealed that formulation containing gelatin-mannitol (3.75% w/v and 3.5% w/v, respectively) with camphor as a volatile pore forming agent exhibited superior properties with disintegration time of less than 10 s. Furthermore, in vitro release studies revealed 90% release of drug from developed dosage form within 10 min, thus suggesting rapid drug dissolution followed by faster onset of action, which forms a strong rationale for development of ODTs of sumatriptan succinate. The developed technology is simple, which involves few steps and can be easily scaled up. Thus, it holds enormous potential for commercial exploitation.
Assuntos
Química Farmacêutica/métodos , Sumatriptana/síntese química , Sumatriptana/metabolismo , Administração Oral , Liofilização/métodos , Humanos , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/metabolismo , Sumatriptana/administração & dosagem , ComprimidosRESUMO
With advances in therapeutic science, apart from drugs, newer bioactive moieties like oligonucleotides, proteins, peptides, enzymes and antibodies are constantly being introduced for the betterment of therapeutic efficacy. These moieties have intracellular components of the cells like cytoplasm and nucleus as one of their pharmacological sites for exhibiting therapeutic activity. Despite their promising efficacy, their intracellular bioavailability has been critically hampered leading to failure in the treatment of numerous diseases and disorders. The endosomal uptake pathway is known to be a rate-limiting barrier for such systems. Bioactive molecules get trapped in the endosomal vesicles and degraded in the lysosomal compartment, necessitating the need for effective strategies that facilitate the endosomal escape and enhance the cytosolic bioavailability of bioactives. Microbes like viruses and bacteria have developed their innate mechanistic tactics to translocate their genome and toxins by efficiently penetrating the host cell membrane. Understanding this mechanism and exploring it further for intracellular delivery has opened new avenues to surmount the endosomal barrier. These strategies include membrane fusion, pore formation and proton sponge effects. On the other hand, progress in designing a novel smart polymeric carrier system that triggers endosomal escape by undergoing modulations in the intracellular milieu has further led to an improvement in intracellular delivery. These comprise pH, enzyme and temperature-induced modulators, synthetic cationic lipids and photo-induced physical disruption. Each of the aforementioned strategies has its own unique mechanism to escape the endosome. This review recapitulates the numerous strategies designed to surmount the bottleneck of endosomal escape and thereby achieve successful intracellular uptake of bioactives.
Assuntos
Permeabilidade da Membrana Celular/fisiologia , Membrana Celular/fisiologia , Endocitose/fisiologia , Endossomos/fisiologia , Nanopartículas/química , Animais , Membrana Celular/química , Difusão , Endossomos/química , Humanos , Modelos BiológicosRESUMO
The goal of this study was to formulate tacrolimus nanogel based on nanostructured lipid carrier (NLC) in order to improve the efficacy, aesthetic, and patient compliance for the treatment of psoriasis. The microemulsion method was used to create phase diagrams and NLCs were prepared using points obtained from the microemulsion region and characterized. The gelling agent carbopol was used to develop an NLC-based nanogel. The pH, drug assay, viscosity, spreadability, and in vitro release of the nanogel, were evaluated. Ex vivo cytotoxicity of the formulation was assessed in murine fibroblast cells. Oxazolone and imiquimod models of psoriasis were used to assess the effectiveness of the nanogel. The NLCs exhibited a submicron particle size of 320 ± 10 nm, a low polydispersity index (<0.3), and a zeta potential of -19.4 mV. Morphological analysis revealed spherical nanoparticles with an encapsulation efficiency of 60 ± 3 %. The nanogel maintained a pH of 6.0 ± 0.5 and possessed a remarkable drug content of 99.73 ± 1.4 %. It exhibited pseudoplastic flow behaviour, ensuring easy spreadability, and demonstrated sustained drug release exceeding 90 % over a 24-hr period. Ex vivo cytotoxicity assessments revealed that the nanogel was safe because no cell death was induced. Nanogel resolved psoriatic blisters, was non-irritating and improved skin elasticity. The favorable properties, safety profile, and remarkable efficacy show the potential of the nanogel as a patient-friendly and effective therapeutic option for psoriasis treatment.
Assuntos
Portadores de Fármacos , Liberação Controlada de Fármacos , Lipídeos , Nanogéis , Psoríase , Tacrolimo , Psoríase/tratamento farmacológico , Animais , Portadores de Fármacos/química , Camundongos , Lipídeos/química , Lipídeos/administração & dosagem , Tacrolimo/administração & dosagem , Tacrolimo/química , Tacrolimo/farmacocinética , Nanogéis/química , Preparações de Ação Retardada , Tamanho da Partícula , Nanoestruturas/química , Nanoestruturas/administração & dosagem , Nanopartículas/química , Imunossupressores/administração & dosagem , Imunossupressores/química , Masculino , Imiquimode/administração & dosagem , Fibroblastos/efeitos dos fármacos , Química Farmacêutica/métodos , Géis , Polietilenoglicóis/química , Polietilenoglicóis/administração & dosagem , PolietilenoiminaRESUMO
The majority of research on nanomaterials has been concentrated on metal nanoparticles since they are easily made and manipulated. Nanomaterials have shown a wide range of applications in biology. Nevertheless, their bioactivity declines due to their extreme susceptibility to and novel Se@ZIF-8 by chemical method. The sizes and morphologies of Se (0) and Se@ZIFchemical and physical stimuli. The goal of encapsulating these nanomaterials in a matrix is gradually being pursued, which boosts their affordability, stability, and usability. Metal-organic frameworks, often known as MOFs, have the potential to be the best platforms for encapsulating metal nanoparticles due to their well-defined frameworks, persistent porosity, and flexibility in modification. In this investigation, we report the synthesis and optimization of polyvinylpyrrolidone-stabilized Se(0) nanoparticles -8 were affected by the ratios of Se/Zn2+and [hmim]/Zn2+used. The optimized Se@ZIF-8 nanoparticles exhibited a particle size and zeta potential of 319 nm and -34 mv respectively. Transmission electron microscopy displayed spherical morphology for Se(0) nanoparticles, whereas the surface morphology of novel Se@ZIF-8 nanoparticles was drastically changed to hexagonal shaped structures with smooth surface morphologies in scanning electron microscopy (SEM). The DTA, TG/DTG, XRD analysis confirmed the presence of novel Se incorporated ZIF-8 nanoparticulate framework. The synthesized novel Se@ZIF-8 nanoparticles showed efficient antibacterial activity as evidenced by low MIC values. Interestingly, these Se@ZIF-8 NPs not only inhibited biofilm formation inS. marcescens,but also effectively eradicated mature biofilms by degrading the eDNA of the EPS layer. It was validated by confocal laser scanning microscopy and SEM analysis. It was observed that Se@ZIF-8 targeted the Quroum Sensing pathway and reduced its associated virulence factors production. This work opens up a different approach of Se@ZIF-8 nanoparticles as novel antibiotics to treat biofilm-associated infections caused byS. marcescensand offer a solution for antimicrobial resistance.
Assuntos
Antibacterianos , Biofilmes , Estruturas Metalorgânicas , Percepção de Quorum , Biofilmes/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Tamanho da Partícula , Selênio/química , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Nanopartículas/química , Teste de Materiais , Povidona/química , Zinco/química , Zinco/farmacologia , Microscopia Eletrônica de Transmissão , ImidazóisRESUMO
Hydrogels are highly biocompatible biomaterials composed of crosslinked three-dimensional networks of hydrophilic polymers. Owing to their natural origin, polysaccharide-based hydrogels (PBHs) possess low toxicity, high biocompatibility and demonstrate in vivo biodegradability, making them great candidates for use in various biomedical devices, implants, and tissue engineering. In addition, many polysaccharides also show additional biological activities such as antimicrobial, anticoagulant, antioxidant, immunomodulatory, hemostatic, and anti-inflammatory, which can provide additional therapeutic benefits. The porous nature of PBHs allows for the immobilization of antibodies, aptamers, enzymes and other molecules on their surface, or within their matrix, potentiating their use in biosensor devices. Specific polysaccharides can be used to produce transparent hydrogels, which have been used widely to fabricate ocular implants. The ability of PBHs to encapsulate drugs and other actives has been utilized for making neural implants and coatings for cardiovascular devices (stents, pacemakers and venous catheters) and urinary catheters. Their high water-absorption capacity has been exploited to make superabsorbent diapers and sanitary napkins. The barrier property and mechanical strength of PBHs has been used to develop gels and films as anti-adhesive formulations for the prevention of post-operative adhesion. Finally, by virtue of their ability to mimic various body tissues, they have been explored as scaffolds and bio-inks for tissue engineering of a wide variety of organs. These applications have been described in detail, in this review.
Assuntos
Hidrogéis , Engenharia Tecidual , Engenharia Tecidual/métodos , Materiais Biocompatíveis , Alicerces Teciduais , Polissacarídeos/farmacologiaRESUMO
The dry powder inhaler (DPI) stands out as a highly patient-friendly and effective pulmonary formulation, surpassing traditional and other pulmonary dosage forms in certain disease conditions. The development of DPI products, however, presents more complexities than that of other dosage forms, particularly in device design and the integration of the drug formulation. This review focuses on the capabilities of DPI devices in pulmonary drug delivery, with a special emphasis on device design and formulation development. It also discusses into the principles of deep lung particle deposition and device engineering, and provides a current overview of the market for DPI devices. Furthermore, the review highlights the use of computational fluid dynamics (CFD) in DPI product design and discusses the regulatory environment surrounding these devices.
Assuntos
Sistemas de Liberação de Medicamentos , Inaladores de Pó Seco , Desenho de Equipamento , Humanos , Administração por Inalação , HidrodinâmicaRESUMO
Antibody-drug conjugates (ADCs) provide effective cancer treatment through the selective delivery of cytotoxic payloads to the cancer cells. They offer unparalleled precision and specificity in directing drugs to cancer cells while minimizing off-target effects. Despite several advantages, there is a requirement for innovations in the molecular design of ADC owing to drug resistance, cancer heterogeneity along the adverse effects of treatment. The review critically analyses ADC function mechanisms, unraveling the intricate interplay between antibodies, linkers, and payloads in facilitating targeted drug delivery to cancer cells. The article also highlights notable advancements in antibody engineering, which aid in creating highly selective and potent ADCs. Additionally, the review details significant progress in clinical ADC development with an in-depth examination of pivotal trials and approved formulations. Antibody Drug Conjugates (ADCs) are a ground-breaking approach to targeted drug delivery, especially in cancer treatment. They offer unparalleled precision and specificity in directing drugs to cancer cells while minimizing off-target effects. This review provides a comprehensive examination of the current state of ADC development, covering their design, mechanisms of action, and clinical applications. The article emphasizes the need for greater precision in drug delivery and explains why ADCs are necessary.
Assuntos
Sistemas de Liberação de Medicamentos , Imunoconjugados , Neoplasias , Humanos , Imunoconjugados/administração & dosagem , Imunoconjugados/uso terapêutico , Imunoconjugados/química , Imunoconjugados/farmacologia , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/uso terapêuticoRESUMO
In the realm of arterial disease interventions, drug-eluting stents (DES) have become a vital therapeutic choice in preventing atherosclerotic plaque formation and restenosis and facilitating vessel healing. Sirolimus-encapsulated poly Lactic-co-Glycolic acid (PLGA) Microparticles (MPs) were developed using solvent evaporation. MPs were freeze-dried with a cryoprotectant and coated on the stent surface using an efficient and reproducible nitrogen-assisted spray coating technique. The MPs displayed a uniform distribution particle size of 4.38 ± 1.1 µm, span value of 0.88 ± 0.02, coating mass transfer efficiency of 13.45 ± 1.1 % on the stent, and a coating time of ≤ 2 min per stent. Post sterilization, the particle size and morphology of the coated stents remained unchanged. Accelerated in vitro drug release profiles were evaluated under different conditions, indicating significant influences based on dissolution methods ranging from 28.2 %±4.3 %, 42.5 %±5.3 %, 76.6 %±4.7 %, and 84.25 %±3.1 % for dialysis bag (DB), vessel simulating flow-through cell (vFTC), flow-through cell (FTC), and sample and separate (SS) technique respectively for 48 h. The drug release mechanism from the coated stents is governed by the combination of the Korsmeyer Peppas and Higuchi models. The developed dissolution method exhibited discriminative effectiveness when evaluated with critical formulation attributes and process parameter variations. The 48 h accelerated drug release studies correlated well with the 6-month real-time release rate with an R2 value of 0.9142 and Pearson's R2 of 0.9561. Ex-vivo studies demonstrated the permeation of MPs into artery tissues. Stability studies confirmed that MPs coated stents maintained desired properties at 4 °C and 30 °C/65 % RH for 6 months. Overall, these findings contribute to advancing stent technology, suggesting the potential for improvement of arterial interventions and enhanced patient outcomes.
RESUMO
In the pursuit of achieving better therapeutic outcomes in the treatment of HIV, innovative drug delivery strategies have been extensively explored. Mannose receptors, which are primarily found on macrophages and dendritic cells, offer promising targets for drug delivery due to their involvement in HIV pathogenesis. This review article comprehensively evaluates recent drug delivery system advancements targeting the mannose receptor. We have systematically described recent developments in creating and utilizing drug delivery platforms, including nanoparticles, liposomes, micelles, noisomes, dendrimers, and other nanocarrier systems targeted at the mannose receptor. These strategies aim to enhance drug delivery specificity, bioavailability, and therapeutic efficacy while decreasing off-target effects and systemic toxicity. Furthermore, the article delves into how mannose receptors and HIV interact, highlighting the potential for exploiting this interaction to enhance drug delivery to infected cells. The review covers essential topics, such as the rational design of nanocarriers for mannose receptor recognition, the impact of physicochemical properties on drug delivery performance, and how targeted delivery affects the pharmacokinetics and pharmacodynamics of anti-HIV agents. The challenges of these novel strategies, including immunogenicity, stability, and scalability, and future research directions in this rapidly growing area are discussed. The knowledge synthesis presented in this review underscores the potential of mannose receptor-based targeted drug delivery as a promising avenue for advancing HIV treatment. By leveraging the unique properties of mannose receptors, researchers can design drug delivery systems that cater to individual needs, overcome existing limitations, and create more effective and patient-friendly treatments in the ongoing fight against HIV/AIDS.
Assuntos
Fármacos Anti-HIV , Sistemas de Liberação de Medicamentos , Infecções por HIV , Lectinas Tipo C , Receptor de Manose , Lectinas de Ligação a Manose , Receptores de Superfície Celular , Humanos , Lectinas Tipo C/metabolismo , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/farmacocinética , Receptores de Superfície Celular/metabolismo , Infecções por HIV/tratamento farmacológico , Lectinas de Ligação a Manose/metabolismo , Animais , NanopartículasRESUMO
DNA origami is a cutting-edge nanotechnology approach that creates precise and detailed 2D and 3D nanostructures. The crucial feature of DNA origami is how it is created, which enables precise control over its size and shape. Biocompatibility, targetability, programmability, and stability are further advantages that make it a potentially beneficial technique for a variety of applications. The preclinical studies of sophisticated programmable nanomedicines and nanodevices that can precisely respond to particular disease-associated triggers and microenvironments have been made possible by recent developments in DNA origami. These stimuli, which are endogenous to the targeted disorders, include protein upregulation, pH, redox status, and small chemicals. Oncology has traditionally been the focus of the majority of past and current research on this subject. Therefore, in this comprehensive review, we delve into the intricate world of DNA origami, exploring its defining features and capabilities. This review covers the fundamental characteristics of DNA origami, targeting DNA origami to cells, cellular uptake, and subcellular localization. Throughout the review, we emphasised on elucidating the imperative for such a therapeutic platform, especially in addressing the complexities of cardiovascular disease (CVD). Moreover, we explore the vast potential inherent in DNA origami technology, envisioning its promising role in the realm of CVD treatment and beyond.
Assuntos
Doenças Cardiovasculares , DNA , Nanoestruturas , Humanos , Doenças Cardiovasculares/terapia , Doenças Cardiovasculares/tratamento farmacológico , DNA/química , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Animais , Nanotecnologia/métodos , Nanomedicina/métodos , Conformação de Ácido NucleicoRESUMO
The microbiome is increasingly implicated in playing a role in physiology and pharmacology; in this review, we investigate the literature on the possibility of bacterial influence on the pharmacology of anti-asthmatic drugs, and the potential impact this has on asthmatic patients. Current knowledge in this area of research reveals an interaction between the gut and lung microbiome and the development of asthma. The influence of microbiome on the pharmacokinetics and pharmacodynamics of anti-asthmatic drugs is limited; however, understanding this interaction will assist in creating a more efficient treatment approach. This literature review highlighted that bioaccumulation and biotransformation in the presence of certain gut bacterial strains could affect drug metabolism in anti-asthmatic drugs. Furthermore, the bacterial richness in the lungs and the gut can influence drug efficacy and could also play a role in drug response. The implications of the above findings suggest that the microbiome is a contributing factor to an individuals' pharmacological response to anti-asthmatic drugs. Hence, future directions for research should follow investigating how these processes affect asthmatic patients and consider the role of the microbiome on drug efficacy and modify treatment guidelines accordingly.