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1.
J Microencapsul ; : 1-22, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967562

RESUMO

Osteoarthritis (OA), affecting around 240 million people globally is a major threat. Currently, available drugs only treat the symptoms of OA; they cannot reverse the disease's progression. The delivery of drugs to afflicted joints is challenging because of poor vasculature of articular cartilage results in their less bioavailability and quick elimination from the joints. Recently approved drugs such as KGN and IL-1 receptor antagonists also encounter challenges because of inadequate formulations. Therefore, microspheres could be a potential player for the intervention of OA owing to its excellent physicochemical properties. This review primarily focuses on microspheres of distinct biomaterials acting as cargo for drugs and biologicals via different delivery routes in the effective management of OA. Microspheres can improve the efficacy of therapeutics by targeting strategies at specific body locations. This review also highlights clinical trials conducted in the last few decades.

2.
AAPS PharmSciTech ; 25(6): 149, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38954224

RESUMO

Silibinin (SIL) Encapsulated Nanoliquid Crystalline (SIL-NLCs) particles were prepared to study neuroprotective effect against amyloid beta (Aß1-42) neurotoxicity in Balb/c mice model. Theses NLCs were prepared through hot emulsification and probe sonication technique. The pharmacodynamics was investigatigated on Aß1-42 intracerebroventricular (ICV) injected Balb/c mice. The particle size, zeta potential and drug loading were optimized to be 153 ± 2.5 nm, -21 mV, and 8.2%, respectively. Small angle X-ray (SAXS) and electron microscopy revealed to crystalline shape of SIL-NLCs. Thioflavin T (ThT) fluroscence and circular dichroism (CD) technique were employed to understand monomer inhibition effect of SIL-NLCs on Aß1-4. In neurobehavioral studies, SIL-NLCs exhibited enhanced mitigation of memory impairment induced on by Aß1-42 in T-maze and new object recognition test (NORT). Whereas biochemical and histopathological estimation of brain samples showed reduction in level of Aß1-42 aggregate, acetylcholine esterase (ACHE) and reactive oxygen species (ROS). SIL-NLCs treated animal group showed higher protection against Aß1-42 toxicity compared to free SIL and Donopezil (DPZ). Therefore SIL-NLCs promises great prospect in neurodegenerative diseases such as Alzheimer's disease.


Assuntos
Peptídeos beta-Amiloides , Camundongos Endogâmicos BALB C , Fármacos Neuroprotetores , Fragmentos de Peptídeos , Silibina , Animais , Peptídeos beta-Amiloides/toxicidade , Peptídeos beta-Amiloides/metabolismo , Camundongos , Silibina/farmacologia , Silibina/administração & dosagem , Fragmentos de Peptídeos/toxicidade , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/administração & dosagem , Masculino , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Tamanho da Partícula , Nanopartículas/química , Espécies Reativas de Oxigênio/metabolismo , Modelos Animais de Doenças , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Acetilcolinesterase/metabolismo
3.
Curr Pharm Des ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38874046

RESUMO

Over the period of the preceding decade, artificial intelligence (AI) has proved an outstanding performance in entire dimensions of science including pharmaceutical sciences. AI uses the concept of machine learning (ML), deep learning (DL), and neural networks (NNs) approaches for novel algorithm and hypothesis development by training the machines in multiple ways. AI-based drug development from molecule identification to clinical approval tremendously reduces the cost of development and the time over conventional methods. The COVID-19 vaccine development and approval by regulatory agencies within 1-2 years is the finest example of drug development. Hence, AI is fast becoming a boon for scientific researchers to streamline their advanced discoveries. AI-based FDA-approved nanomedicines perform well as target selective, synergistic therapies, recolonize the theragnostic pharmaceutical stream, and significantly improve drug research outcomes. This comprehensive review delves into the fundamental aspects of AI along with its applications in the realm of pharmaceutical life sciences. It explores AI's role in crucial areas such as drug designing, drug discovery and development, traditional Chinese medicine, integration of multi-omics data, as well as investigations into drug repurposing and polypharmacology studies.

4.
Int J Biol Macromol ; 271(Pt 2): 132280, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38744364

RESUMO

The successful tissue engineering depends on the development of biologically active scaffolds that possess optimal characteristics to effectively support cellular functions, maintain structural integrity and aid in tissue regeneration. Hydrogels have emerged as promising candidates in tissue regeneration due to their resemblance to the natural extracellular matrix and their ability to support cell survival and proliferation. The integration of hydrogel scaffold into the polymer has a variable impact on the pseudo extracellular environment, fostering cell growth/repair. The modification in size, shape, surface morphology and porosity of hydrogel scaffolds has consequently paved the way for addressing diverse challenges in the tissue engineering process such as tissue architecture, vascularization and simultaneous seeding of multiple cells. The present review provides a comprehensive update on hydrogel production using natural and synthetic biomaterials and their underlying mechanisms. Furthermore, it delves into the application of hydrogel scaffolds in tissue engineering for cardiac tissues, cartilage tissue, adipose tissue, nerve tissue and bone tissue. Besides, the present article also highlights various clinical studies, patents, and the limitations associated with hydrogel-based scaffolds in recent times.


Assuntos
Materiais Biocompatíveis , Hidrogéis , Engenharia Tecidual , Alicerces Teciduais , Hidrogéis/química , Humanos , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Animais , Materiais Biocompatíveis/química , Regeneração/efeitos dos fármacos
5.
Chem Sci ; 15(17): 6544-6551, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38699273

RESUMO

The development of an efficient strategy for facile access to quinoline-based bis-heterocycles holds paramount importance in medicinal chemistry. Herein, we describe a unified approach for accessing 8-(indol-3-yl)methyl-quinolines by integrating Cp*Rh(iii)-catalyzed C(sp3)-H bond activation of 8-methylquinolines followed by nucleophilic cyclization with o-ethynylaniline derivatives. Remarkably, methoxybiaryl ynones under similar catalytic conditions delivered quinoline tethered spiro[5.5]enone scaffolds via a dearomative 6-endo-dig C-cyclization. Moreover, leveraging this method for C8(sp2)-H bond activation of quinoline-N-oxide furnished biologically relevant oxindolyl-quinolines. This reaction proceeds via C(sp2)-H bond activation, regioselective alkyne insertion, oxygen-atom-transfer (OAT) and intramolecular nucleophilic cyclization in a cascade manner. One C-C, one C-N and one C[double bond, length as m-dash]O bond were created with concomitant formation of a quaternary center.

6.
Acta Crystallogr B Struct Sci Cryst Eng Mater ; 80(Pt 3): 163-170, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38682692

RESUMO

Hydrogen-bonding and halogen-bonding interactions are important noncovalent interactions that play a significant role in the crystal structure of organic molecules. An in-depth analysis is given of the crystal packing of two previously reported crystal structures of dihalogenated 1,2,4-triazole derivatives, namely 3,5-dichloro-1H-1,2,4-triazole and 3,5-dibromo-1H-1,2,4-triazole. This work provides insights into the complex interplay of hydrogen-bonding and halogen-bonding interactions resulting in the formation of multiple trimeric motifs in the crystal structure of 1,2,4-triazole derivatives. Analysis of the crystal packing of these isostructural crystal structures revealed that the molecular arrangement in these molecules is primarily stabilized by the formation of different trimeric motifs stabilized by N-H...N hydrogen bonds, N-H...X (X = Cl/Br) halogen bonds and C-X...X halogen-bonding interactions. Computational studies further revealed that all these trimers are energetically stable. A crystallographic database search further reveals that while the cyclic trimers reported in this study are present in other molecules, structures analyzed in this study are the sole instances where all are present simultaneously.

7.
Mol Neurobiol ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558360

RESUMO

Blood-brain barrier (BBB) is a distinguishing checkpoint that segregates peripheral organs from neural compartment. It protects the central nervous system from harmful ambush of antigens and pathogens. Owing to such explicit selectivity, the BBB hinders passage of various neuroprotective drug molecules that escalates into poor attainability of neuroprotective agents towards the brain. However, few molecules can surpass the BBB and gain access in the brain parenchyma by exploiting surface transporters and receptors. For successful development of brain-targeted therapy, understanding of BBB transporters and receptors is crucial. This review focuses on the transporter and receptor-based mechanistic pathway that can be manoeuvred for better comprehension of reciprocity of receptors and nanotechnological vehicle delivery. Nanotechnology has emerged as one of the expedient noninvasive approaches for brain targeting via manipulating the hurdle of the BBB. Various nanovehicles are being reported for brain-targeted delivery such as nanoparticles, nanocrystals, nanoemulsion, nanolipid carriers, liposomes and other nanovesicles. Nanotechnology-aided brain targeting can be a strategic approach to circumvent the BBB without altering the inherent nature of the BBB.

8.
Int J Biol Macromol ; 266(Pt 1): 131048, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522697

RESUMO

Past scientific testimonials in the field of glioma research, the deadliest tumor among all brain cancer types with the life span of 10-15 months after diagnosis is considered as glioblastoma multiforme (GBM). Even though the availability of treatment options such as chemotherapy, radiotherapy, and surgery, are unable to completely cure GBM due to tumor microenvironment complexity, intrinsic cellular signalling, and genetic mutations which are involved in chemoresistance. The blood-brain barrier is accountable for restricting drugs entry at the tumor location and related biological challenges like endocytic degradation, short systemic circulation, and insufficient cellular penetration lead to tumor aggression and progression. The above stated challenges can be better mitigated by small interfering RNAs (siRNA) by knockdown genes responsible for tumor progression and resistance. However, siRNA encounters with challenges like inefficient cellular transfection, short circulation time, endogenous degradation, and off-target effects. The novel functionalized nanocarrier approach in conjunction with biological and chemical modification offers an intriguing potential to address challenges associated with the naked siRNA and efficiently silence STAT3, coffilin-1, EGFR, VEGF, SMO, MGMT, HAO-1, GPX-4, TfR, LDLR and galectin-1 genes in GBM tumor. This review highlights the nanoengineered siRNA carriers, their recent advancements, future perspectives, and strategies to overcome the systemic siRNA delivery challenges for glioma treatment.


Assuntos
Neoplasias Encefálicas , Glioma , RNA Interferente Pequeno , Humanos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/uso terapêutico , Glioma/genética , Glioma/terapia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Nanopartículas/química , Animais , Portadores de Fármacos/química , Terapia Genética/métodos
9.
AAPS PharmSciTech ; 25(3): 41, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38366178

RESUMO

Viral infections represent a significant threat to global health due to their highly communicable and potentially lethal nature. Conventional antiviral interventions encounter challenges such as drug resistance, tolerability issues, specificity concerns, high costs, side effects, and the constant mutation of viral proteins. Consequently, the exploration of alternative approaches is imperative. Therefore, nanotechnology-embedded drugs excelled as a novel approach purporting severe life-threatening viral disease. Integrating nanomaterials and nanoparticles enables ensuring precise drug targeting, improved drug delivery, and fostered pharmacokinetic properties. Notably, nanocrystals (NCs) stand out as one of the most promising nanoformulations, offering remarkable characteristics in terms of physicochemical properties (higher drug loading, improved solubility, and drug retention), pharmacokinetics (enhanced bioavailability, dose reduction), and optical properties (light absorptivity, photoluminescence). These attributes make NCs effective in diagnosing and ameliorating viral infections. This review comprises the prevalence, pathophysiology, and resistance of viral infections along with emphasizing on failure of current antivirals in the management of the diseases. Moreover, the review also highlights the role of NCs in various viral infections in mitigating, diagnosing, and other NC-based strategies combating viral infections. In vitro, in vivo, and clinical studies evident for the effectiveness of NCs against viral pathogens are also discussed.


Assuntos
Nanopartículas , Viroses , Humanos , Preparações Farmacêuticas/química , Disponibilidade Biológica , Sistemas de Liberação de Medicamentos , Viroses/tratamento farmacológico , Nanopartículas/química , Antivirais/farmacologia , Antivirais/uso terapêutico
10.
J Am Chem Soc ; 146(12): 8659-8667, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38407928

RESUMO

The solid-state synthesis of single-crystalline organic polymers, having functional properties, remains an attractive and developing research area in polymer chemistry and materials science. However, light-triggered topochemical synthesis of crystalline polymers comprising an organoboron backbone has not yet been reported. Here, we describe an intriguing example of single-crystal-to-single-crystal (SCSC) rapid photosynthesis (occurs on a seconds-scale) of two structurally different linear organoboron polymers, driven by environmentally sustainable visible/sun light, obtained from the same monomer molecule. A newly designed Lewis acid-base type molecular B ← N organoboron adduct (consisting of an organoboron core and naphthylvinylpyridine ligands) crystallizes in two solid-state forms featuring the same chemical structure but different 3D structural topologies, namely, monomers 1 and 2. The solvate molecule-free crystals of 1 undergo topochemical photopolymerization via an unusual olefin-naphthyl ring [2 + 2] cyclization to yield the single crystalline [3]-ladderane polymer 1P growing along the B ← N linkages, accompanied by instantaneous and violent macroscopic mechanical motions or photosalient effects (such as bending-reshaping and jumping motions). In contrast, visible light-harvesting single crystals of 2 quantitatively polymerize to a B ← N bond-stabilized polymer 2P in a SCSC fashion owing to the rapid [2 + 2] cycloaddition reaction among olefin double bonds. Such olefin bonds in the crystals of 2 are suitably preorganized for photoreaction due to the presence of solvate molecules in the crystal packing. Single crystals of 2 also show photodynamic jumping motions - in response to visible light but in a relatively slower fashion than the crystals of 1. In addition to SCSC topochemical polymerization and dynamic motions, both monomer crystals and their single-crystalline polymers feature green emissive and short-lived room-temperature phosphorescence properties upon excitation with visible-light wavelength.

11.
J Drug Target ; 32(4): 347-364, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38253594

RESUMO

PRIMARY OBJECTIVE: The primary objective of the review is to assess the potential of lymphatic-targeted drug delivery systems, with a particular emphasis on their role in tumour therapy and vaccination efficacy. REASON FOR LYMPHATIC TARGETING: The lymphatic system's crucial functions in maintaining bodily equilibrium, regulating metabolism, and orchestrating immune responses make it an ideal target for drug delivery. Lymph nodes, being primary sites for tumour metastasis, underscore the importance of targeting the lymphatic system for effective treatment. OUTCOME: Nanotechnologies and innovative biomaterials have facilitated the development of lymphatic-targeted drug carriers, leveraging endogenous macromolecules to enhance drug delivery efficiency. Various systems such as liposomes, micelles, inorganic nanomaterials, hydrogels, and nano-capsules demonstrate significant potential for delivering drugs to the lymphatic system. CONCLUSION: Understanding the physiological functions of the lymphatic system and its involvement in diseases underscores the promise of targeted drug delivery in improving treatment outcomes. The strategic targeting of the lymphatic system presents opportunities to enhance patient prognosis and advance therapeutic interventions across various medical contexts, indicating the importance of ongoing research and development in this area.


Assuntos
Vasos Linfáticos , Nanopartículas , Neoplasias , Humanos , Nanopartículas/química , Sistemas de Liberação de Medicamentos , Sistema Linfático/metabolismo , Neoplasias/metabolismo
12.
Drug Deliv Transl Res ; 14(1): 1-16, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37552393

RESUMO

Vincristine (VCR) is a chemotherapeutic agent obtained from natural alkaloid plant source Catharanthus roseus. VCR has been significantly useful in treatments of lung cancer, lymphocyte-based leukaemia, glioblastomas and acute myeloid leukaemia. VCR attaches to tubulin fibrils and prevents filament polymerization that permanently led to mitosis inhibition in cancer cells. Clinically, VCR is administered to patients in multidrug combination to reduce adverse drug effects and potential blockage of bone marrow inhibition due to prescribed monotherapy. However, VCR possesses low cancer tissue affinity and at higher dose often led to irreversible neurotoxicity. Conventional VCR injectables are successfully used in clinics, but lack of controlled release, non-specific biodistribution and consequent off-target side effects are still major challenges. Currently, nanotechnological drug delivery systems are being explored for improvement of VCR pharmacokinetic profile and tumour-specific targeting. Various nanomedicine formulations such as liposomes, lipid nanoparticles, and polymeric nanocarriers of VCR have been studied under various in vitro and in vivo models. In this review, we have summarised the chemotherapeutic role of VCR, evaluated the mechanism of action, pharmacokinetics and challenges associated with VCR delivery. Moreover, application of VCR in nanomedicine and effect on anticancer efficacy in preclinical and clinical setting are also being discussed.


Assuntos
Antineoplásicos , Neoplasias Pulmonares , Humanos , Vincristina/efeitos adversos , Distribuição Tecidual , Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Neoplasias Pulmonares/tratamento farmacológico
13.
ACS Chem Neurosci ; 15(1): 31-55, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38118278

RESUMO

Neuroinflammation is a key pathophysiological feature of stroke-associated brain injury. A local innate immune response triggers neuroinflammation following a stroke via activating inflammasomes. The nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome has been heavily implicated in stroke pathobiology. Following a stroke, several stimuli have been suggested to trigger the assembly of the NLRP3 inflammasome. Recent studies have advanced the understanding and revealed several new players regulating NLRP3 inflammasome-mediated neuroinflammation. This article discussed recent advancements in NLRP3 assembly and highlighted stroke-induced mitochondrial dysfunction as a major checkpoint to regulating NLRP3 activation. The NLRP3 inflammasome activation leads to caspase-1-dependent maturation and release of IL-1ß, IL-18, and gasdermin D. In addition, genetic or pharmacological inhibition of the NLRP3 inflammasome activation and downstream signaling has been shown to attenuate brain infarction and improve the neurological outcome in experimental models of stroke. Several drug-like small molecules targeting the NLRP3 inflammasome are in different phases of development as novel therapeutics for various inflammatory conditions, including stroke. Understanding how these molecules interfere with NLRP3 inflammasome assembly is paramount for their better optimization and/or development of newer NLRP3 inhibitors. In this review, we summarized the assembly of the NLRP3 inflammasome and discussed the recent advances in understanding the upstream regulators of NLRP3 inflammasome-mediated neuroinflammation following stroke. Additionally, we critically examined the role of the NLRP3 inflammasome-mediated signaling in stroke pathophysiology and the development of therapeutic modalities to target the NLRP3 inflammasome-related signaling for stroke treatment.


Assuntos
Lesões Encefálicas , Acidente Vascular Cerebral , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Doenças Neuroinflamatórias , Acidente Vascular Cerebral/tratamento farmacológico , Interleucina-1beta/metabolismo
14.
Mol Neurobiol ; 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066399

RESUMO

Wilson disease, a rare genetic disorder resulting from mutations in the ATP7B gene disrupts copper metabolism, leading to its harmful accumulation in hepatocytes, the brain, and other organs. It affects roughly 1 in 30,000 individuals, with 1 in 90 being gene carriers. Beyond gene mutations, the disease involves complex factors contributing to copper imbalance. Ongoing research seeks to unravel intricate molecular pathways, offering fresh insights into the disease's mechanisms. Simultaneously, there is a dedicated effort to develop effective therapeutic strategies. Nanotechnology-driven formulations are showing promise for both treatment and early diagnosis of Wilson disease. This comprehensive review covers the entire spectrum of the condition, encompassing pathophysiology, potential biomarkers, established and emerging therapies, ongoing clinical trials, and innovative nanotechnology applications. This multifaceted approach holds the potential to improve our understanding, diagnosis, and management of Wilson's disease, which remains a challenging and potentially life-threatening disorder.

15.
AAPS PharmSciTech ; 24(8): 223, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37945928

RESUMO

Rivastigmine hydrogen tartrate (RHT) is an acetylcholinesterase (AChE) inhibitor used in the management of Alzheimer's disease (AD). RHT is a BCS class-I drug that undergoes significant first-pass metabolism. Permeating a hydrophilic drug through the brain remains a major challenge in brain delivery. In this study, the RHT was incorporated inside the hydrophilic core of liposomes (LPS) and then coated with the ApoE3. ApoE3-coated RHT-loaded liposomes (ApoE3-RHT-LPS) were fabricated through the thin film hydration method using DSPE-PEG. The coating of LPS with ApoE3 enhances brain uptake and improves Aß clearance. The results obtained from the physicochemical characterization demonstrated that ApoE3-RHT-LPS shows a particle size of 128.6 ± 2.16 nm and a zeta potential of 16.6 ± 1.19. The % entrapment efficiency and % drug loading were found to be 75% and 17.84%, respectively. The data obtained from TEM and SEM studies revealed that the particle size of the LPS was less than 200 nm. An in vitro AChE assay was performed, and the results demonstrated the AChE inhibitory potential of ApoE3-RHT-LPS. Through the intravenous route, an in vivo pharmacokinetic study of formulation displayed improved brain uptake of RHT by ~ 1.3-fold than pure RHT due to ApoE3 coating. In vivo, biodistribution studies in vital organs suggested that the biodistribution of RHT to the liver was significantly reduced (p < 0.001), signifying an increase in the drug's half-life and blood circulation time. All research findings suggested that ApoE3 coating and LPS strategy are proven effective for improving the brain uptake of RHT designed for the management of AD.


Assuntos
Doença de Alzheimer , Lipossomos , Humanos , Rivastigmina , Lipossomos/química , Apolipoproteína E3/metabolismo , Apolipoproteína E3/farmacologia , Acetilcolinesterase/metabolismo , Acetilcolinesterase/farmacologia , Acetilcolinesterase/uso terapêutico , Distribuição Tecidual , Lipopolissacarídeos , Encéfalo/metabolismo , Inibidores da Colinesterase , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Tamanho da Partícula
16.
Phys Chem Chem Phys ; 25(46): 32040-32050, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-37982166

RESUMO

Boron nitrides are very important and are used as lubricants, insulating agents, etc. Interactions of such systems with small molecules are important. This study examined the potential of B3N3 (triboron trinitride) to act as both an electron acceptor and an electron donor in the formation of noncovalent interactions. The anisotropic electronic distribution observed in the electrostatic potential map supported the B3N3's ability to exhibit the predicted electron donor-acceptor duality. Further computational investigations on optimized gas-phase complexes of B3N3:(NH3)n=1-3, B3N3:(NCH)n=1-6, B3N3:(N2H2)n=1-3 and (B3N3)2 confirmed that the B3N3 molecule can participate in B⋯N triel bonding interactions and H···N hydrogen bonding interactions. These energetically stable complexes are primarily governed by electrostatic and polarization interactions.

17.
Biomater Adv ; 154: 213663, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37865027

RESUMO

The current work is focused on developing mannose-coated PLGA nanoparticles for delivering Donepezil and Memantine in one dosage form. The formulated nanoparticles were prepared using a simple emulsification technique. The final coated NPs exhibited 179.4 nm size and - 33.1 mV zeta potential and spherical shape. The concentration of IN-administrated MEM and DPZ mannose coated NPs in brain was ~573 and 207 ng/mL respectively. This amount accounts for 3 times more in comparison to uncoated NPs administered via intranasal and peroral routes. The plasma concentration of coated NPs administered via the intranasal route was various times less in comparison to other groups. In the field of pharmacodynamics, the administration of coated NPs via the IN route has shown superior efficacy in comparison to other groups in various investigations involving neurobehavioral assessments, gene expression analyses and biochemical estimations. The findings indicate that the IN route may be a potential avenue for delivering therapeutic agents using nanoparticles to treat neurological illnesses. This approach shows promise as a viable alternative to traditional dose forms and administration methods.


Assuntos
Memantina , Nanopartículas , Donepezila , Memantina/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ácido Poliglicólico/química , Ácido Láctico/química , Manose , Nanopartículas/química
18.
AAPS PharmSciTech ; 24(7): 179, 2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37658972

RESUMO

Numerous neurodegenerative conditions, such as Alzheimer's, Huntington's, Parkinson's, amyotrophic lateral sclerosis, and glioblastoma multiform are now becoming significant concerns of global health. Formulation-related issues, physiological and anatomical barriers, post-administration obstacles, physical challenges, regulatory limitations, environmental hurdles, and health and safety issues have all hindered successful delivery and effective outcomes despite a variety of treatment options. In the current review, we covered the intranasal route, an alternative strategic route targeting brain for improved delivery across the BBB. The trans-nasal pathway is non-invasive, directing therapeutics directly towards brain, circumventing the barrier and reducing peripheral exposure. The delivery of nanosized vesicles loaded with drugs was also covered in the review. Nanovesicle systems are organised in concentric bilayered lipid membranes separated with aqueous layers. These carriers surmount the disadvantages posed by intranasal delivery of rapid mucociliary clearance and enzymatic degradation, and enhance retention of drug to reach the site of target. In conclusion, the review covers in-depth conclusions on numerous aspects of formulation of drug-loaded vesicular system delivery across BBB, current marketed nasal devices, significant jeopardies, potential therapeutic aids, and current advancements followed by future perspectives.


Assuntos
Glioblastoma , Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/tratamento farmacológico , Nariz , Sistemas de Liberação de Medicamentos , Encéfalo
19.
Biomater Adv ; 154: 213594, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37657277

RESUMO

The rise of tuberculosis (TB) superbugs has impeded efforts to control this infectious ailment, and new treatment options are few. Paradoxical Inflammation (PI) is another major problem associated with current anti-TB therapy, which can complicate the treatment and leads to clinical worsening of disease despite a decrease in bacterial burden in the lungs. TB infection is generally accompanied by an intense local inflammatory response which may be critical to TB pathogenesis. Clofazimine (CLF), a second-line anti-TB drug, delineated potential anti-mycobacterial effects in-vitro and in-vivo and also demonstrated anti-inflammatory potential in in-vitro experiments. However, clinical implications may be restricted owing to poor solubility and low bioavailability rendering a suboptimal drug concentration in the target organ. To unravel these issues, nanocrystals of CLF (CLF-NC) were prepared using a microfluidizer® technology, which was further processed into micro-sized CLF nano-clusters (CLF-NCLs) by spray drying technique. This particle engineering offers combined advantages of micron- and nano-scale particles where micron-size (∼5 µm) promise optimum aerodynamic parameters for the finest lung deposition, and nano-scale dimensions (∼600 nm) improve the dissolution profile of apparently insoluble clofazimine. An inhalable formulation was evaluated against virulent mycobacterium tuberculosis in in-vitro studies and in mice infected with aerosol TB infection. CLF-NCLs resulted in the significant killing of virulent TB bacteria with a MIC value of ∼0.62 µg/mL, as demonstrated by Resazurin microtiter assay (REMA). In TB-infected mice, inhaled doses of CLF-NCLs equivalent to ∼300 µg and âˆ¼ 600 µg of CLF administered on every alternate day over 30 days significantly reduced the number of bacteria in the lung. With an inhaled dose of ∼600 µg/mice, reduction of mycobacterial colony forming units (CFU) was achieved by ∼1.95 Log10CFU times compared to CLF administered via oral gavage (∼1.18 Log10CFU). Lung histology scoring showed improved pathogenesis and inflammation in infected animals after 30 days of inhalation dosing of CLF-NCLs. The levels of pro-inflammatory mediators, including cytokines, TNF-α & IL-6, and MMP-2 in bronchoalveolar lavage fluid (BAL-F) and lung tissue homogenates, were attenuated after inhalation treatment. These pre-clinical data suggest inhalable CLF-NCLs are well tolerated, show significant anti-TB activity and apparently able to tackle the challenge of paradoxical chronic lung inflammation in murine TB model.


Assuntos
Pneumonia , Tuberculose , Camundongos , Animais , Clofazimina/farmacologia , Clofazimina/uso terapêutico , Aerossóis e Gotículas Respiratórios , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Pneumonia/tratamento farmacológico , Inflamação/tratamento farmacológico
20.
Phys Chem Chem Phys ; 25(29): 19427-19434, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37436829

RESUMO

This study investigates the crystal structures of substituted thiophenes and isothiocyanates by utilizing the method of in situ cryo-crystallization to gain quantitative insights into the electronic features of sulfur-centered interactions. This work reveals that the role of sulfur as a "nucleophilic" or "electrophilic" species during non-covalent interaction is significantly influenced by its immediate chemical and electronic surroundings.

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