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1.
Antibiotics (Basel) ; 11(1)2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35052985

RESUMO

Microbial pathogens are the most prevalent cause of chronic infections and fatalities around the world. Antimicrobial agents including antibiotics have been frequently utilized in the treatment of infections due to their exceptional outcomes. However, their widespread use has resulted in the emergence of multidrug-resistant strains of bacteria, fungi, viruses, and parasites. Furthermore, due to inherent resistance to antimicrobial drugs and the host defence system, the advent of new infectious diseases, chronic infections, and the occurrence of biofilms pose a tougher challenge to the current treatment line. Essential oils (EOs) and their biologically and structurally diverse constituents provide a distinctive, inexhaustible, and novel source of antibacterial, antiviral, antifungal, and antiparasitic agents. However, due to their volatile nature, chemical susceptibility, and poor solubility, their development as antimicrobials is limited. Nanoparticles composed of biodegradable polymeric and inorganic materials have been studied extensively to overcome these limitations. Nanoparticles are being investigated as nanocarriers for antimicrobial delivery, antimicrobial coatings for food products, implantable devices, and medicinal materials in dressings and packaging materials due to their intrinsic capacity to overcome microbial resistance. Essential oil-loaded nanoparticles may offer the potential benefits of synergism in antimicrobial activity, high loading capacity, increased solubility, decreased volatility, chemical stability, and enhancement of the bioavailability and shelf life of EOs and their constituents. This review focuses on the potentiation of the antimicrobial activity of essential oils and their constituents in nanoparticulate delivery systems for a wide range of applications, such as food preservation, packaging, and alternative treatments for infectious diseases.

2.
Pharmaceuticals (Basel) ; 14(11)2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34832983

RESUMO

One of the major impediments to drug development is low aqueous solubility and thus poor bioavailability, which leads to insufficient clinical utility. Around 70-80% of drugs in the discovery pipeline are suffering from poor aqueous solubility and poor bioavailability, which is a major challenge when one has to develop an ocular drug delivery system. The outer lipid layer, pre-corneal, dynamic, and static ocular barriers limit drug availability to the targeted ocular tissues. Biopharmaceutical Classification System (BCS) class II drugs with adequate permeability and limited or no aqueous solubility have been extensively studied for various polymer-based solubility enhancement approaches. The hydrophilic nature of cellulosic polymers and their tunable properties make them the polymers of choice in various solubility-enhancement techniques. This review focuses on various cellulose derivatives, specifically, their role, current status and novel modified cellulosic polymers for enhancing the bioavailability of BCS class II drugs in ocular drug delivery systems.

3.
Nat Commun ; 12(1): 6215, 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-34711827

RESUMO

In phenylketonuria (PKU) patients, a genetic defect in the enzyme phenylalanine hydroxylase (PAH) leads to elevated systemic phenylalanine (Phe), which can result in severe neurological impairment. As a treatment for PKU, Escherichia coli Nissle (EcN) strain SYNB1618 was developed under Synlogic's Synthetic Biotic™ platform to degrade Phe from within the gastrointestinal (GI) tract. This clinical-stage engineered strain expresses the Phe-metabolizing enzyme phenylalanine ammonia lyase (PAL), catalyzing the deamination of Phe to the non-toxic product trans-cinnamate (TCA). In the present work, we generate a more potent EcN-based PKU strain through optimization of whole cell PAL activity, using biosensor-based high-throughput screening of mutant PAL libraries. A lead enzyme candidate from this screen is used in the construction of SYNB1934, a chromosomally integrated strain containing the additional Phe-metabolizing and biosafety features found in SYNB1618. Head-to-head, SYNB1934 demonstrates an approximate two-fold increase in in vivo PAL activity compared to SYNB1618.

4.
Expert Opin Drug Deliv ; 18(11): 1741-1760, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34605347

RESUMO

INTRODUCTION: Chronic wounds are a substantial burden on the healthcare system. Their treatment requires advanced dressings, which can provide a moist wound environment, prevent bacterial infiltration, and act as a drug carrier. Cellulose is biocompatible, biodegradable, and can be functionalized according to specific requirements, which makes it a highly versatile biomaterial. Antimicrobial cellulose dressings are proving to be highly effective against infected wounds. AREAS COVERED: This review briefly addresses the mechanism of wound healing and its pathophysiology. It also discusses wound infections, biofilm formation, and progressive emergence of drug-resistant bacteria in chronic wounds and the treatment strategies for such types of infected wounds. It also summarizes the general properties, method of production, and types of cellulose wound dressings. It explores recent studies and advancements regarding the use of cellulose and its derivatives in wound management. EXPERT OPINION: Cellulose and its various functionalized derivatives represent a promising choice of wound dressing material. Cellulose-based dressings loaded with antimicrobials are very useful in controlling infection in a chronic wound. Recent studies showing its efficacy against drug-resistant bacteria make it a favorable choice for chronic wound infections. Further research and large-scale clinical trials are required for better clinical evidence of its efficiency.


Assuntos
Materiais Biocompatíveis , Infecção dos Ferimentos , Bandagens , Celulose , Humanos , Cicatrização , Infecção dos Ferimentos/tratamento farmacológico
5.
Crit Rev Ther Drug Carrier Syst ; 38(4): 79-107, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34369740

RESUMO

Several ocular drug delivery (ODD) systems, like hydrogels, microparticles, nano-emulsions, micro-emulsions, and liposomes have been researched, which can govern the drug release and sustain therapeutic levels for a delayed period in the eye. While new drugs targeting methods to the eye are possible by various nanoparticles. Presently in the market, there are fewer choices and need for novel nano-ocular delivery systems as well as therapies for prolonged delivery to the anterior and posterior eye segments. The primary objective of this article is to summarize current discoveries and proven activities of different nano- and microsystems in ODD. This article also depicts some regulatory updates along with the patents granted to the inventor for their work on ODD. Overall, a thought of how the different forthcoming of nanotechnologies like nanoparticles and nanomedicine can be used to investigate the frontiers of ODD and treatment can be withdrawn by this article.


Assuntos
Oftalmopatias , Nanopartículas , Sistemas de Liberação de Medicamentos , Olho , Oftalmopatias/tratamento farmacológico , Humanos , Lipossomos
6.
Curr Drug Deliv ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238183

RESUMO

OBJECTIVE: The objective of this study was to develop and optimize a microflora-triggered colon targeted sustained-release dosage form using gum ghatti (GG) and hydroxypropyl methylcellulose (HPMC K100). METHODS: GG and HPMC K100 were used to prepare microflora triggered colon targeted sustained-release dosage form. For evaluation, two different tablets comprising metoprolol succinate and mesalamine as an active ingredient were used with the objective of developing a platform technology for various categories of drugs. The tablets were coated with Eudragit® L100 and Eudragit® S100 to provide enteric coating and evaluated for hardness, thickness, friability, weight variation, disintegration, and drug content. In vitro release studies for the prepared tablets were carried out mimicking the physiological transit time. Further, the effects of microflora were evaluated using rat cecal content. RESULTS: The in vitro dissolution profile of coated matrix tablets showed that 86.03±0.43% of metoprolol succinate and 80.26±0.67% of mesalamine were released at the end of 12 h. The ex vivo dissolution profile of coated matrix tablets showed that 96.50±0.27% of metoprolol succinate and 92.58±0.39% of mesalamine were released at the end of 12 h in the presence of rat ceacal content. The developed formulation was stable when subjected to the standard ICH stability study conditions. CONCLUSION: The result of this study showed that gum ghatti together with hydroxypropyl methylcellulose could be successfully used for the preparation of microflora triggered colon targeted matrix tablets.

7.
Int J Dermatol ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34310695

RESUMO

The skin is the largest organ of the integumentary system with a multifunctional purpose to protect the body from heat and microbes, regulate body temperature, and act as a sensory organ. A topical dosage form applied on the skin will have to cross the stratum corneum, which would then allow the dosage form to traverse the subsequent layers of the skin. The drug with poor solubility and short half-life would serve as an ideal candidate for its delivery via the transdermal route. This review reports the role of natural oils in enhancing the permeation of drugs through skin as they possess different features like natural origin, favorable penetration enhancement, and partitioning action in the skin. Chemical penetration enhancers have been used widely but are associated with toxicities. Thus, more research should be channelized in the area of extraction of oils from natural sources, along with their active constituents, which can serve as therapeutic alternatives to various disorders and diseases. Natural oils are obtained from leaves, fruits, flowers, seeds, bark, and roots, which have a therapeutic potential as well as penetration enhancing activity. The demerits of oral drug delivery include degradation of drugs in the gastrointestinal tract, addition of taste masking, and coating of tablets, which can be overcome by delivering the drug via the transdermal route. Natural oil contains lipids, flavonoids, and terpenes, which play a significant role in anti-inflammatory and penetration enhancing activity.

8.
Pharmacol Ther ; 226: 107871, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33915179

RESUMO

Bladder cancer is the 10th most commonly occurring malignancy worldwide with a 75% of 5-year survival rate, while it ranks 13th among the deaths occurring due to cancer. The majority of bladder cancer cases are diagnosed at an early stage and 70% are of non-invasive grade. However, 70% of these cases develop chemoresistance and progress to the muscle invasive stage. Conventional chemotherapy treatments are unsuccessful in curbing chemoresistance, bladder cancer progression while having an adverse side effect, which is mainly due to off-target drug distribution. Therefore, new drug delivery strategies, new therapeutics and therapies or their combination are being explored to develop better treatments. In this regard, nanotechnology has shown promise in the targeted delivery of therapeutics to bladder cancer cells. This review discusses the recent discovery of new therapeutics (chemotherapeutics, immunotherapeutic, and gene therapies), recent developments in the delivery of therapeutics using nano drug delivery systems, and the combination treatments with FDA-approved therapies, i.e., hyperthermia and photodynamic therapy. We also discussed the potential of other novel drug delivery systems that are minimally explored in bladder cancer. Lastly, we discussed the clinical status of therapeutics and therapies for bladder cancer. Overall, this review can provide a summary of available treatments for bladder cancer, and also provide opportunities for further development of drug delivery systems for better management of bladder cancer.

9.
Expert Opin Drug Deliv ; 18(9): 1261-1290, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33793359

RESUMO

INTRODUCTION: The targeted delivery of anticancer agents to tumor is a major challenge because most of the drugs show off-target effect resulting in nonspecific cell death. Multifunctionalized metallic nanoparticles (NPs) are explored as new carrier system in the era of cancer therapeutics. Researchers investigated the potential of metallic NPs to target tumor cells by active and passive mechanisms, thereby reducing off-target effects of anticancer agents. Moreover, photocatalytic activity of upconversion nanoparticles (UCNPs) and the enhanced permeation and retention (EPR) effect have also gained wide potential in cancer treatment. Recent advancement in the field of nanotechnology highlights their potency for cancer therapy. AREAS COVERED: This review summarizes the types of gold and silver metallic NPs with targeting mechanisms and their potentiality in cancer therapy. EXPERT OPINION: Recent advances in the field of nanotechnology for cancer therapy offer high specificity and targeting efficiency. Targeting tumor cells through mechanistic pathways using metallic NPs for the disruption/alteration of molecular profile and survival rate of the tumor cells has led to an effective approach for cancer therapeutics. This alteration in the survival rate of the tumor cells might decrease the proliferation thereby resulting in more efficient management in the treatment of cancer.


Assuntos
Antineoplásicos , Nanopartículas Metálicas , Neoplasias , Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Humanos , Nanotecnologia , Neoplasias/tratamento farmacológico
10.
Mater Sci Eng C Mater Biol Appl ; 121: 111875, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33579498

RESUMO

Osteosarcoma is the most commonly diagnosed form of bone cancer. It is characterized by a high risk of developing lung metastasis as the disease progresses. Standard treatment includes combination of surgical intervention, chemotherapy and radiotherapy. However, the non-specificity of potent chemotherapeutic agents often leads to major side effects. In this review, we discuss the role of various classes of biomaterials, including both organic as well as inorganic in realizing the local and systemic delivery of therapeutic agents like drugs, radioisotopes and even gene silencing agents to treat osteosarcoma. Biomaterial assisted unconventional therapies such as targeted therapy, nanotherapy, magnetic hyperthermia, gene therapy, photothermal and photodynamic therapies are also being explored. A wide variety of biomaterials including lipids, carbon-based materials, polymers, silica, bioactive glass, hydroxyapatite and metals are designed as delivery systems with the desired loading efficiency, release profile, and on-demand delivery. Among others, liposomal carriers have attracted a great deal of attention due to their capability to encapsulate both hydrophobic and hydrophilic drugs. Polymeric systems have high drug loading efficiency and stability and can even be tailored to achieve desired size and physiochemical properties. Carbon-based systems can also be seen as an upcoming class of therapeutics with great potential in treating different types of cancer. Inorganic materials like silica nanoparticles have high drug payload owing to their mesoporous structure. On the other hand, ceramic materials like bioactive glass and hydroxyapatite not only act as excellent delivery vectors but also participate in osteo-regeneration activity. These multifunctional biomaterials are also being investigated for their theranostic abilities to monitor cancer ablation. This review systematically discusses the vast landscape of biomaterials along with their challenges and respective opportunities for osteosarcoma therapy.


Assuntos
Nanopartículas , Osteossarcoma , Materiais Biocompatíveis , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Humanos , Osteossarcoma/terapia , Dióxido de Silício
11.
Molecules ; 26(2)2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33430478

RESUMO

Nanotechnology-based development of drug delivery systems is an attractive area of research in formulation driven R&D laboratories that makes administration of new and complex drugs feasible. It plays a significant role in the design of novel dosage forms by attributing target specific drug delivery, controlled drug release, improved, patient friendly drug regimen and lower side effects. Polysaccharides, especially chitosan, occupy an important place and are widely used in nano drug delivery systems owing to their biocompatibility and biodegradability. This review focuses on chitosan nanoparticles and envisages to provide an insight into the chemistry, properties, drug release mechanisms, preparation techniques and the vast evolving landscape of diverse applications across disease categories leading to development of better therapeutics and superior clinical outcomes. It summarizes recent advancement in the development and utility of functionalized chitosan in anticancer therapeutics, cancer immunotherapy, theranostics and multistage delivery systems.


Assuntos
Quitosana/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Nanomedicina Teranóstica , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/farmacocinética , Fenômenos Químicos , Portadores de Fármacos/síntese química , Nanomedicina Teranóstica/métodos
12.
Curr Drug Targets ; 22(7): 722-733, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33213339

RESUMO

Colorectal carcinogenesis involves various processes from the accumulation of genetic alterations to genetic and epigenetic modulations and chromosomal abnormalities. It also involves mutations in oncogenes and tumour suppressor genes. Genomic instability plays a vital role in CRC. Advances in modern biological techniques and molecular level studies have identified various genes involved in colorectal cancer (CRC). KRAS, BRAF, PI3K, and p53 genes play a significant role in different phases of CRC. Alteration of these genes leads to development or progression and metastasis colon cancer. This review focuses on the role of KRAS, BRAF, PI3KCA, and TP53 genes in carcinogenesis and their significance in various stages of CRC. It also provides insights on specific modulators acting on these genes. Further, this review discusses the mechanism of the pathways involving these genes in carcinogenesis and current molecules and treatment options under various stages of clinical evaluation.


Assuntos
Neoplasias do Colo , Carcinogênese , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Humanos , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Fatores de Transcrição/genética , Proteína Supressora de Tumor p53/genética
13.
Expert Opin Drug Deliv ; 18(2): 169-185, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32921169

RESUMO

INTRODUCTION: Epilepsy, a major neurological disorder affects about 1% of the Indian population. The discovery of noninvasive strategies for epilepsy presents a challenge for the scientists. Different types of nose-to-brain dosage-forms have been studied for epilepsy management. It aims to give new perspectives for developing new and existing anti-epileptic drugs. Combining nanotechnology with nose-to-brain approach can help in promoting the treatment efficacy by site-specific delivery. Also, it will minimize the side-effects and patient noncompliance observed in conventional administration routes. Peptide delivery can be an interesting approach for the management of epilepsy. Drug-loaded intranasal nanoformulations exhibit diverse prospective potentials in the management of epilepsy. Considering that, nanotherapy using nose-to-brain delivery as a prospective technique for the efficient management of epilepsy is reviewed. AREAS COVERED: The authors have compiled all recently available data pertaining to the nose-to-brain delivery of therapeutics using nanotechnological strategies. The fundamental mechanism of nose-to-brain delivery, claims for intranasal delivery and medical devices for epilepsy are discussed. EXPERT OPINION: Drug-loaded intranasal nanoformulations exhibit different prospective potentials in the management of epilepsy. Considering the foregoing research done in the field of nanotechnology, globally, authors propose nose-to-brain delivery of nanoformulations as a potential technique for the efficient management of epilepsy.


Assuntos
Epilepsia , Preparações Farmacêuticas , Administração Intranasal , Encéfalo , Sistemas de Liberação de Medicamentos , Epilepsia/tratamento farmacológico , Humanos , Nanotecnologia , Mucosa Nasal , Estudos Prospectivos
14.
Drug Metab Pers Ther ; 35(3)2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32827392

RESUMO

Objectives Patients with serious injury need special care and treatment to control the infection, as wound sepsis is one of the major causes of death. Silver sulfadiazine (SSD) is widely used as an antimicrobial agent which promotes healing and re-epithelialization. However, due to certain drawbacks such as inflammation and cytotoxicity, the need for novel drug delivery modality emerges. The objective of this study was to develop natural polymeric (chitosan and gelatin) hydrogel sponges containing SSD and evaluate its efficacy in wound healing using animal models. Methods SSD containing hydrogel sponges were prepared by solvent casting technique. Scanning electron microscopy (SEM) and Differential scanning calorimetry (DSC) were used to evaluate morphological characteristics of the hydrogel sponges. Anti-thrombogenic property, drug release studies, drug release kinetics, antimicrobial property, and wound healing effect were also studied in detail. Results The optimized batch of hydrogel sponges (CG4) consists of 1% SSD wt., 10% wt. Gelatin, 1% wt. Chitosan and honey 7.5% wt. as plasticizer. At the 12th hour, in vitro and ex vivo drug release was found to be 76.994±0.67% and 24.22±0.57% respectively. CG4 batch had enhanced in vitro antimicrobial activity as compared to conventional marketed cream. The developed SSD hydrogel sponges showed a faster rate of wound healing as compared to a marketed cream. Animals treated with CG4 formulation showed complete angiogenesis and re-epithelialization by 8th day, whereas 12 days were required for complete wound healing with marketed cream. Conclusions The prepared hydrogel sponges can serve as a potential alternative for wound healing dressing as compared to the marketed product.


Assuntos
Antibacterianos/farmacologia , Bandagens , Hidrogéis/farmacologia , Sulfadiazina de Prata/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/química , Bactérias/efeitos dos fármacos , Quitosana/química , Quitosana/farmacologia , Modelos Animais de Doenças , Fungos/efeitos dos fármacos , Gelatina/química , Gelatina/farmacologia , Humanos , Hidrogéis/química , Ratos , Ratos Wistar , Sulfadiazina de Prata/química
15.
Nat Commun ; 11(1): 2739, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32483165

RESUMO

Synthetic biology is a powerful tool to create therapeutics which can be rationally designed to enable unique and combinatorial functionalities. Here we utilize non-pathogenic E coli Nissle as a versatile platform for the development of a living biotherapeutic for the treatment of cancer. The engineered bacterial strain, referred to as SYNB1891, targets STING-activation to phagocytic antigen-presenting cells (APCs) in the tumor and activates complementary innate immune pathways. SYNB1891 treatment results in efficacious antitumor immunity with the formation of immunological memory in murine tumor models and robust activation of human APCs. SYNB1891 is designed to meet manufacturability and regulatory requirements with built in biocontainment features which do not compromise its efficacy. This work provides a roadmap for the development of future therapeutics and demonstrates the transformative potential of synthetic biology for the treatment of human disease when drug development criteria are incorporated into the design process for a living medicine.


Assuntos
Escherichia coli/imunologia , Imunoterapia/métodos , Proteínas de Membrana/imunologia , Neoplasias/terapia , Transdução de Sinais/imunologia , Animais , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , Linhagem Celular Tumoral , Escherichia coli/genética , Escherichia coli/metabolismo , Engenharia Genética/métodos , Humanos , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neoplasias/genética , Neoplasias/imunologia , Fagócitos/imunologia , Fagócitos/metabolismo , Transdução de Sinais/genética , Biologia Sintética/métodos , Biologia Sintética/tendências
16.
Drug Deliv Transl Res ; 10(5): 1288-1301, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32277353

RESUMO

The objective of the present work was to develop and optimize multiparticulate pH-dependent bioadhesive pellets of curcumin and cyclosporine for the management of intestinal bowel disease (IBD). The bioadhesive sustained release pellets were intended for targeting the affected site for an improved therapeutic effect. Bioadhesive pellet cores of curcumin and cyclosporine were formulated using Carbopol 940 (CP940) and hydroxypropyl cellulose (HPC-H) by the extrusion/spheronization method, and drug delivery to the colon was controlled by the pH-sensitive polymer Eudragit® S100. Microcrystalline cellulose (Avicel PH101) was found to be the best forming agent for pellet core. The ratio of CP940 to HPC-H was kept at 1:1 to achieve 100% bioadhesion. The in vitro dissolution profiles of coated pellets depicted that 12.327 ± 0.342% of curcumin and 14.751 ± 0.112% of cyclosporine were released at the end of 6 h (at pH 6.8), whereas 71.278 ± 0.100% of curcumin and 76.76 ± 0.195% of cyclosporine were released at the end of 24 h (at pH 7.4). The drug release profile was found to follow zero-order kinetics for both drugs. The selected formulation was evaluated on an acetic acid-induced ulcerative colitis in the rat model to evaluate the efficiency of drug-loaded pellets coated with Eudragit®S100. The pharmacodynamic study revealed the therapeutic efficacy of Eudragit®S100-coated pellets of curcumin and cyclosporine in alleviating the conditions of the acetic acid-induced colitis model as reflected by weight gain as well as improvement of clinical, macroscopic and microscopic parameters of induced colitis, as compared with free curcumin and cyclosporine. The combination of curcumin and cyclosporine has been proven to have a synergistic effect for the successful management of IBD when used in a low dose as compared with individual drugs with high doses. Hence, curcumin- and cyclosporine-loaded bioadhesive pellets may act as a promising targeted drug delivery system in the management of IBD. Graphical abstract.


Assuntos
Colite , Curcumina , Ciclosporina , Doenças Inflamatórias Intestinais , Animais , Colite/tratamento farmacológico , Colo , Curcumina/administração & dosagem , Ciclosporina/administração & dosagem , Sistemas de Liberação de Medicamentos , Concentração de Íons de Hidrogênio , Doenças Inflamatórias Intestinais/tratamento farmacológico , Ratos , Solubilidade
17.
Expert Opin Drug Deliv ; 17(7): 903-918, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32347124

RESUMO

INTRODUCTION: Human immunodeficiency virus (HIV) targets and modulates the immune system increasing the risk of other associated infections. Highly active antiretroviral therapy (HAART) has significantly improved AIDS-associated morbidity, but has limitations of adverse effects, frequent dosing regimen leading to medical non-adherence. Drug delivery systems that target HIV reservoirs could potentially reduce dose-dependent toxicity and the duration of treatment. The major cellular HIV reservoirs are macrophages and CD4+ T cells with macrophages being responsible for carrying and spreading the virus. The crucial involvement of macrophages in the pathogenesis of HIV infection has led to development of macrophage targeted nanocarrier delivery systems. AREAS COVERED: Eradication of viral reservoirs like HIV-infected macrophages has emerged to be a fundamental barrier and challenge for complete eradication of HIV from the immune system. Literature reports several macrophage targeted nanocarrier delivery systems developed as either functionalized or non-functionalized formulations such as liposomes, ethosomes, polymeric nanoparticles, dendrimers, and solid lipid nanoparticles showcasing superior efficacy over the conventional antiretroviral delivery systems. EXPERT OPINION: The development of fixed dose combination of antiretroviral drugs into macrophage targeted delivery systems should factor in the inherent plasticity and heterogeneity of macrophages that is dependent on their microenvironment. A rational selection of nanocarriers will facilitate selectivity and enhanced efficacy of antiretroviral drugs accompanied by reduced dosing and toxicity. Such macrophage targeted delivery systems would positively impact the therapeutic outcomes in the management of HIV infection.


Assuntos
Sistemas de Liberação de Medicamentos , Infecções por HIV/tratamento farmacológico , Nanopartículas , Fármacos Anti-HIV/administração & dosagem , Humanos , Lipídeos/química , Lipossomos , Macrófagos/metabolismo , Polímeros/química
18.
Drug Deliv Transl Res ; 10(4): 962-974, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32170657

RESUMO

Increasing incidences of sexually transmitted disease including human papillomavirus (HPV), herpes simplex virus (HSV), and human immunodeficiency virus (HIV) infection in women have triggered the need for developing user-friendly potential prophylactic approach. Presently, although several therapeutic moieties are in place but none of them have prophylactic action, they are confined to provide symptomatic relief to the patient-researchers which have now recognized the need for discovering efficient topical prophylactic agents. One of these with great potential topical microbicide uncovered is vaginal delivery of small interfering RNA (siRNA). siRNA delivery involves silencing gene expression in a sequence specific manner in causative agent thereby exhibiting microbicide activity. However, the mucosal barrier and physiological changes in vagina such as pH and variable epithelial layer thickness during menstrual cycle serve as major hurdles for efficient delivery and cellular uptake of siRNA. In order to enhance vaginal delivery of siRNA, nanocarrier systems like lipid-based delivery systems, macromolecular systems, polymeric nanoparticles, aptamer and cell-penetrating peptides have been investigated widely until date. The present article elaborates on various nanocarriers and their promising outcomes at preclinical stage and future implications of nanocarrier-based siRNA vaginal delivery. Graphical abstract Overview on barriers to the delivery of siRNA by vaginal route and nanocarrier envisaged until date for enhancing efficient delivery of siRNA.


Assuntos
Nanopartículas/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Administração Intravaginal , Animais , Feminino , Humanos , Vagina
19.
Toxicol Appl Pharmacol ; 377: 114631, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31228495

RESUMO

Despite an incessant advancement in the treatment of Colorectal Cancer (CRC), 40% of individuals suffer from disease relapse which marks the need for new treatment options. In this study we report synergistic antitumor activity of Laccaic acid (LA) and Phenethyl isothiocyanate (PEITC) combination in colorectal cancer via dual inhibition of DNA methyltransferase-1 and Histone deacetylase-1. Efficacy of combination was evaluated in both in-vitro and in-vivo experiments using human colon carcinoma cell line HT29 and 1,2-dimethyl hydrazine induced colon cancer rat model, respectively. In the cell line studies treatment with combination showed reduced cell viability with apoptotic cell death compared to individual treatment groups which showed necrotic cell death. IC50 value for combination (0.478 µM) was much lower than LA (6.08 µM), PEITC (11.88 µM) and 5-Fluorouracil (9.88 µM). In the in-vivo study combination group significantly attenuated number of aberrant crypt foci, fecal consistency score, IL-6, TNF-α, DNMT1 and HDAC1 levels, histological findings and mortality as compared to negative control. Further, toxic effects produced by combination were significantly less. Results suggest potent synergistic efficacy of Laccaic acid and Phenethyl isothiocyanate combination in colorectal cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Compostos Azo/farmacologia , Neoplasias Colorretais/tratamento farmacológico , DNA (Citosina-5-)-Metiltransferase 1/antagonistas & inibidores , Histona Desacetilase 1/antagonistas & inibidores , Isotiocianatos/farmacologia , Animais , Antimetabólitos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/enzimologia , Fluoruracila/farmacologia , Células HT29 , Humanos , Masculino , Necrose , Ratos , Ratos Sprague-Dawley
20.
Expert Opin Drug Deliv ; 16(7): 687-699, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31111766

RESUMO

INTRODUCTION: Coinfection with Mycobacterium tuberculosis is the leading cause of death in HIV positive patients. In 2017, about 0.3 million HIV positive people died of tuberculosis. There is high load of mycobacteria and HIV in the lungs and eradication of the same is vital for patient survival. AREAS COVERED: This review focuses on the pathogenesis of HIV-TB coinfection and the current management approaches of this coinfection. It presents a detailed discussion of current investigations in novel drug delivery systems for effective targeting of HIV-TB lung reservoirs, especially via pulmonary drug delivery. Additionally, emphasis is given to the need of HIV-TB cotargeting, an unmet need in management of HIV-TB coinfection. EXPERT OPINION: To achieve the goal of complete eradication of HIV-TB reservoirs in lungs requires focused research strategies to be undertaken in the area of pulmonary delivery systems. These endeavors could eventually lead to better patient compliance and improved treatment outcomes. The treatment regimen of HIV-TB coinfection is associated with a major drawback of low therapeutic concentration of drugs in lungs. Nanotechnology provides an excellent platform for delivery of anti-TB and anti-HIV drugs via the pulmonary route thereby serving as a viable and effective means of managing the mycobacterial and HIV reservoirs in the lungs.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Antituberculosos/administração & dosagem , Infecções por HIV/tratamento farmacológico , Tuberculose/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Humanos , Mycobacterium tuberculosis
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