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The diagnosis and treatment of neurological ailments always remain an utmost challenge for research fraternity due to the presence of BBB. The intranasal route appeared as an attractive and alternative route for brain targeting of therapeutics without the intrusion of BBB and GI exposure. This route directly and effectively delivers the therapeutics to different regions of the brain via olfactory and trigeminal nerve pathways. However, shorter drug retention time and mucociliary clearance curtail the efficiency of the intranasal route. The in situ mucoadhesive gel overthrow the limitations of direct nose-to-brain delivery by not only enhancing nasal residence time but also minimizing the mucociliary clearance and enzymatic degradation. This delivery system further improves the nasal absorption as well as bioavailability of drugs in the brain. The in situ mucoadhesive gel is a controlled and sustained release system that facilitates the absorption of various proteins, peptides and other larger lipophilic and hydrophilic moieties. Owing to multiple benefits, in situ gelling system has been widely explored to target the brain via nasal route. However, very few review works are reported which explains the application of in situ nasal gel for brain delivery of CNS acting moieties. Hence, in this piece of work, we have initially discussed the global statistics of neurological disorders reported by WHO and other reputed organizations, nasal anatomy, mechanism and challenges of nose-to-brain drug delivery. The work mainly focused on the use of different stimuli-responsive polymers, specifically thermoresponsive, pH-responsive, and ion triggered systems for the development of an effective and controlled dosage form, i.e., in situ nasal gel for brain targeting of bioactives. We have also highlighted the origin, structure, nature and phase transition behavior of the smart polymers found suitable for nasal administration, including poloxamer, chitosan, EHEC, xyloglucan, Carbopol, gellan gum and DGG along with their application in the treatment of neurological disorders. The article is aimed to gather all the information of the past 10 years related to the development and application of stimuli-responsive in situ nasal gel for brain drug delivery., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In last two decades, the lipid nanocarriers have been extensively investigated for their drug targeting efficiency towards the critical areas of the human body like CNS, cardiac region, tumor cells, etc. Owing to the flexibility and biocompatibility, the lipid-based nanocarriers, including nanoemulsion, liposomes, SLN, NLC etc. have gained much attention among various other nanocarrier systems for brain targeting of bioactives. Across different lipid nanocarriers, NLC remains to be the safest, stable, biocompatible and cost-effective drug carrier system with high encapsulation efficiency. Drug delivery to the brain always remains a challenging issue for scientists due to the complex structure and various barrier mechanisms surrounding the brain. The application of a suitable nanocarrier system and the use of any alternative route of drug administration like nose-to-brain drug delivery could overcome the hurdle and improves the therapeutic efficiency of CNS acting drugs thereof. NLC, a second-generation lipid nanocarrier, upsurges the drug permeation across the BBB due to its unique structural properties. The biocompatible lipid matrix and nano-size make it an ideal drug carrier for brain targeting. It offers many advantages over other drug carrier systems, including ease of manufacturing and scale-up to industrial level, higher drug targeting, high drug loading, control drug release, compatibility with a wide range of drug substances, non-toxic and non-irritant behavior. This review highlights recent progresses towards the development of NLC for brain targeting of bioactives with particular reference to its surface modifications, formulations aspects, pharmacokinetic behavior and efficacy towards the treatment of various neurological disorders like AD, PD, schizophrenia, epilepsy, brain cancer, CNS infection (viral and fungal), multiple sclerosis, cerebral ischemia, and cerebral malaria. This work describes in detail the role and application of NLC, along with its different fabrication techniques and associated limitations. Specific emphasis is given to compile a summary and graphical data on the area explored by scientists and researchers worldwide towards the treatment of neurological disorders with or without NLC. The article also highlights a brief insight into two prime approaches for brain targeting, including drug delivery across BBB and direct nose-to-brain drug delivery along with the current global status of specific neurological disorders., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this modern era, with the help of various advanced technologies, medical science has overcome most of the health-related issues successfully. Though, some diseases still remain unresolved due to various physiological barriers. One such condition is Alzheimer; a neurodegenerative disorder characterized by progressive memory impairment, behavioral abnormalities, mood swing and disturbed routine activities of the person suffering from. It is well known to all that the brain is entirely covered by a protective layer commonly known as blood brain barrier (BBB) which is responsible to maintain the homeostasis of brain by restricting the entry of toxic substances, drug molecules, various proteins and peptides, small hydrophilic molecules, large lipophilic substances and so many other peripheral components to protect the brain from any harmful stimuli. This functionally essential structure creates a major hurdle for delivery of any drug into the brain. Still, there are some provisions on BBB which facilitate the entry of useful substances in the brain via specific mechanisms like passive diffusion, receptor-mediated transcytosis, carrier-mediated transcytosis etc. Another important factor for drug transport is the selection of a suitable drug delivery systems like, liposome, which is a novel drug carrier system offering a potential approach to resolving this problem. Its unique phospholipid bilayer structure (similar to physiological membrane) had made it more compatible with the lipoidal layer of BBB and helps the drug to enter the brain. The present review work focused on various surface modifications with functional ligand (like lactoferrin, transferrin etc.) and carrier molecules (such as glutathione, glucose etc.) on the liposomal structure to enhance its brain targeting ability towards the successful treatment of Alzheimer disease., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Application of pharmaceutical nanotechnology (nanomedicines) for plant actives and extracts, is gaining a tremendous growth and interest among the scientists. This emerging herbal revolution has headed towards the development of another approaches for the delivery of poorly soluble herbal bioactives and plant extracts for enhancing their bioavailability and efficacy. In the same context, a majority of pharmaceutical nanotechnologies and targeting strategies including phytosomes, nanoparticles, hydrogels, microspheres, transferosomes and ethosomes, self nano emulsifying drug delivery systems (SNEDDS), self micro emulsifying drug delivery systems (SMEDDS) has been applied for the delivery of bioactives and plant extracts and were identified and explored. These pharmaceutical nanotechnologies have been proven to be the most efficient and reliable delivery systems, as these enhance the solubility, absorption, pharmacokinetics, bioavailability and provide protection from toxicity. Considering these aspects, the present review highlights the present scenario related to the expansion of novel herbal formulations utilizing the nanotechnologies and compilation of their delivery types and mechanism, methodology, loaded drug, drug size, entrapment efficiency of drug, in vivo activity and its application. Moreover, this review article provides an understanding of therapeutic efficacy of the herbal medicines to be loaded into the novel drug delivery system for various biomedical applications., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Drug induced hemolysis is a frequent complication associated with chemotherapy. It results from interaction of drug with erythrocyte membrane and leads to cell lysis. In recent past, various approaches were made to reduce drug-induced hemolysis, which includes drug polymer conjugation, drug delivery via colloidal carriers and hydrogels, co-administration of botanical agents and modification in molecular chemistry of drug molecules. The basic concept behind these strategies is to protect the red blood cells from membrane damaging effects of drugs. There are several examples of drug polymer conjugate that either are approved by Food and Drug Administration or are under clinical trial for delivering drugs with reduced toxicities. Likewise, colloidal carriers are also used successfully nowadays for the delivery of various chemotherapeutic agents like gemcitabine and amphotericin B with remarkable decrease in their hemolytic activity. Similarly, co-administration of botanical agents with drugs works as secondary system proving protection and strength to erythrocyte membranes. In addition to the above statement, interaction hindrance between RBC and drug molecule by molecular modification plays an important role in reducing hemolysis. This review predominantly describes the above recent approaches explored to achieve the reduced hemolytic activity of drugs especially chemotherapeutic agents., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Stimuli triggered polymers provide a variety of applications related with the biomedical fields. Among various stimuli triggered mechanisms, thermoresponsive mechanisms have been extensively investigated, as they are relatively more convenient and effective stimuli for biomedical applications. In a contemporary approach for achieving the sustained action of proteins, peptides and bioactives, injectable depots and implants have always remained the thrust areas of research. In the same series, Poloxamer based thermogelling copolymers have their own limitations regarding biodegradability. Thus, there is a need to have an alternative biomaterial for the formulation of injectable hydrogel, which must remain biocompatible along with safety and efficacy. In the same context, poly(ethylene glycol) (PEG) based copolymers play a crucial role as a biomedical material for biomedical applications, because of their biocompatibility, biodegradability, thermosensitivity and easy controlled characters. This review stresses on the physicochemical property, stability and composition prospects of smart PEG/poly(lactic-co-glycolic acid) (PLGA) based thermoresponsive injectable hydrogels, recently utilized for biomedical applications. The manuscript also highlights the synthesis scheme and stability characteristics of these copolymers, which will surely help the researchers working in the same area. We have also emphasized the applied use of these smart copolymers along with their formulation problems, which could help in understanding the possible modifications related with these, to overcome their inherent associated limitations., (© 2013.)

Emulgel is an emerging topical drug delivery system to which if more effort is paid towards its formulation & development with more number of topically effective drugs it will prove a boon for derma care & cosmetology. Emulgels are either emulsion of oil in water or water in oil type, which is gelled by mixing it with gelling agent. Incorporation of emulsion into gel increases its stability & makes it a dual control release system. Due to lack of excess oily bases & insoluble excipients, it shows better drug release as compared to other topical drug delivery system. Presence of gel phase makes it a non greasy & favors good patient compliance. These reviews give knowledge about Emulgel including its properties, advantages, formulation considerations, and its recent advances in research field. All factors such as selection of gelling agent, oil agent, emulsifiers influencing the stability and efficacy of Emulgel are discussed. All justifications are described in accordance with the research work carried out by various scientists. These brief reviews on formulation method have been included. Current research works that carried out on Emulgel are also discussed and highlighted the wide utility of Emulgel in topical drug delivery system. After the vast study, it can be concluded that the Emulgels appear better & effective drug delivery system as compared to other topical drug delivery system. The comprehensive analysis of rheological and release properties will provide an insight into the potential usage of Emulgel formulation as drug delivery system., (© 2013.)

The phyto-phospholipid complexation technique has emerged as one of the leading methods of improving bioavailability of phytopharmaceuticals having poor competency of solubilizing and crossing the biological membranes. Several plant actives in spite having potent in vitro pharmacological activities have failed to demonstrate similar in vivo response. Such plant actives have been made more effective systemically by incorporating them with dietary phospholipids forming new cellular structures which are amphipathic in nature. In the last few years phospholipids have been extensively explored for improved bioavailability and efficacy of plant drugs. Further, it is also much relevant to mention that phospholipids show unique compatibility with biological membranes and have inherent hepatoprotective activity. Different methods have been adopted to formulate phospholipid complexes of plant extractives utilizing varying solvent systems, molar ratios of drug/phospholipids and different drying techniques. Some methods of formulating such drug-phospholipid complexes have been patented as well. However, the stability of phyto-phospholipid complexes is still a matter of concern which needs attention. But still a number of products exploiting this technique are under clinical trials and some of them are now in market. The current review highlights key findings of recent years with our own viewpoints which can give the new directions to this strategy and also includes advancements in the technical aspects of phyto-phospholipid formulations which have been done in the recent past with future challenges., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Transdermal drug delivery system (TDDS) utilizes the skin as executable route for drug administration but the foremost barrier against drug permeability is the stratum corneum and therefore, it limits therapeutic bioavailability of the bioactive. This review focuses on the recent advancements in the TDDS which include iontophoresis, sonophoresis, electroporation, microneedles, magnetophoresis, photomechanical waves and electron beam irradiation. These advancements are exhaustively discussed with techniques involved with their beneficial claims for different categories of bioactive. However, a lot of research has been carried out in TDDS, still the system has many pros and cons such as inconsistent drug release, prevention of burst release formulation and problems related to toxicity. In addition to that, to exploit the TDDS more efficiently scientists have worked on some combinational approaches for manufacturing TDDS viz., chemical-iontophoresis, chemical-electroporation, chemical-ultrasound, iontophoresis-ultrasound, electroporation-iontophoresis electroporation-ultrasound and pressure waves-chemicals and reported the synergistic effect of the same for safe, effective and practical use of TDDS. The present article covers all the above-mentioned aspects in detail and hence the article will assuredly serve as an enlightening tool for the visionaries working in the concerned area., (Copyright © 2012 Elsevier B.V. All rights reserved.)