RESUMEN
Blood-Brain Barrier (BBB) acts as a highly impermeable barrier, presenting an impediment to the crossing of most classical drugs targeted for neurodegenerative diseases including Parkinson's disease (PD). About the nature of drugs and other potential molecules, they impose unavoidable doserestricted limitations eventually leading to the failure of therapy. However, many advancements in formulation technology and modification of delivery approaches have been successful in delivering the drug to the brain in the therapeutic window. The nose to the brain (N2B) drug delivery employing the nanoformulation, is one such emerging delivery approach, overcoming both classical drug formulation and delivery-associated limitations. This latter approach offers increased bioavailability, greater patient acceptance, lesser metabolic degradation of drugs, circumvention of BBB, ample drug loading along with the controlled release of the drugs. In N2B delivery, the intranasal (IN) route carries therapeutics firstly into the nasal cavity followed by the brain through olfactory and trigeminal nerve connections linked with nasal mucosa. The N2B delivery approach is being explored for delivering other biologicals like neuropeptides and mitochondria. Meanwhile, this N2B delivery system is associated with critical challenges consisting of mucociliary clearance, degradation by enzymes, and drug translocations by efflux mechanisms. These challenges finally culminated in the development of suitable surfacemodified nano-carriers and Focused- Ultrasound-Assisted IN as FUS-IN technique which has expanded the horizons of N2B drug delivery. Hence, nanotechnology, in collaboration with advances in the IN route of drug administration, has a diversified approach for treating PD. The present review discusses the physiology and limitation of IN delivery along with current advances in nanocarrier and technical development assisting N2B drug delivery.
Asunto(s)
Sistemas de Liberación de Medicamentos , Nanotecnología , Mucosa Nasal , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/terapia , Encéfalo/metabolismo , Barrera Hematoencefálica/metabolismo , Mucosa Nasal/inervación , Mucosa Nasal/metabolismoRESUMEN
Non-small cell lung cancer (NSCLC) is a leading cause of death in millions of cancer patients. Lack of diagnosis at an early stage in addition to no specific guidelines for its treatment, and a higher rate of treatment- related toxicity further deteriorate the conditions. Current therapies encompass surgery, chemotherapy, radiation therapy, and immunotherapy according to the pattern and the stage of lung cancer. Among all, with a longlasting therapeutic action, reduced side-effects, and a higher rate of survival, therapeutic cancer vaccine is a new, improved strategy for treating NSCLC. Immunoadjuvants are usually incorporated into the therapeutic vaccines to shield the antigen against environmental and physiological harsh conditions in addition to boosting the immune potential. Conventional immunoadjuvants are often associated with an inadequate cellular response, poor target specificity, and low antigen load. Recently, inhalable polymeric nano/micro immunoadjuvants have exhibited immense potential in the development of therapeutic vaccines for the treatment of NSCLC with improved mucosal immunization. The development of polymeric micro/nano immunoadjuvants brought a new era for vaccines with increased strength and efficiency. Therefore, in the present review, we explained the potential application of micro/nano immunoadjuvants for augmenting the stability and efficacy of inhalable vaccines in the treatment of NSCLC. In addition, the role of biodegradable, biocompatible, and non-toxic polymers has also been discussed with case studies.
Asunto(s)
Vacunas contra el Cáncer , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adyuvantes Inmunológicos/uso terapéutico , Vacunas contra el Cáncer/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Polímeros/uso terapéuticoRESUMEN
Curcumin, a natural polyphenolic compound extracted from rhizomes of Curcuma longa (turmeric), a plant in the ginger family (Zingiberaceae) has been used worldwide and extensively in Southeast Asia. Curcumin exhibited numerous biological and pharmacological activities including potent antioxidant, cardiovascular disease, anticancer, anti-inflammatory effects and neurodegenerative disorders in cell cultures and animal models. Hence, the present study was designed in order to explore the possible neuroprotective role of curcumin against rotenone induced cognitive impairment, oxidative and mitochondrial dysfunction in mice. Chronic administration of rotenone (1mg/kg i.p.) for a period of three weeks significantly impaired cognitive function (actophotometer, rotarod and open field test), oxidative defense (increased lipid peroxidation, nitrite concentration and decreased activity of superoxide dismutase, catalase and reduced glutathione level) and mitochondrial complex (II and III) enzymes activities as compared to normal control group. Three weeks of curcumin (50, 100 and 200mg/kg, p.o.) treatment significantly improved behavioral alterations, oxidative damage and mitochondrial enzyme complex activities as compared to negative control (rotenone treated) group. Curcumin treated mice also mitigated enhanced acetylcholine esterase enzyme level as compared to negative control group. We found that curcumin restored motor deficits and enhanced the activities of antioxidant enzymes suggesting its antioxidant potential in vivo. The findings of the present study conclude neuroprotective role of curcumin against rotenone induced Parkinson's in mice and offer strong justification for the therapeutic prospective of this compound in the management of PD.