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Although paclitaxel is a front-line chemotherapeutic agent for the treatment of metastatic breast cancer, its intravenous therapy produces deleterious adverse effects. In an attempt to address the issue, the present study aimed to develop a paclitaxel loaded thermosensitive/thermoresponsive hydrogel (PTXNp-TGel) for loco-regional administration to breast tumors to provide dose-dense chemotherapy. Poloxamer and xanthan gum were used to prepare TGel by the cold method. In vitro and in vivo performance of PTXNp-TGel was compared with TGel, pure drug loaded TGel (PTX-TGel) and marketed formulation, Taxol®. The formulated PTXNp-TGel showed acceptable gelation temperature and time (37 °C and 57 s), lower viscosity at room temperature and higher viscosity at body temperature to support sol-gel transition with increasing temperature, and sustained drug release up to 21 days. Additionally, PTXNp-TGel showed negligible hemolytic toxicity as compared to PTX-TGel and Taxol®. Intratumoral administration of PTXNp-TGel produced significantly higher antitumor activity as indicated by lowest relative tumor volume (1.50) and relative antitumor proliferation rate (27.71 %) in comparison with PTX-TGel, Taxol®, and PTXNp (p 0.05). Finally, insignificant body weight loss during the experimental period, lack of hematotoxicity, nephrotoxicity, and hepatotoxicity imply improved therapeutic performance of the locally administrated dose-dense therapy of PTXNp-TGel as compared to Taxol®.

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.

Psoriasis is a consistently recurring, inflammatory, autoimmune disorder of the skin, affecting about 2-5% of the world population. Abundant therapeutic agents are accessible for the treatment of psoriasis. Nevertheless, none of them are entirely secure and effective to treat the disease without compromising patient compliance. Furthermore, already existing drugs are supposed to restrain the ailment and alleviate the sign and symptoms with no complete cure. However, they focus on restraining the disease and alleviating the symptoms without providing an absolute cure. Therefore there remains a vital challenge, to explore a new drug moiety or delivery system which could safely and effectively manage psoriasis without compromising patient compliance. Furthermore, conventional formulations offer reduced benefit/risk ratio of anti-psoriatic drugs, which limits the use of existing conventional formulations. Novel formulations based on nanocarriers are a promising prospect to overcome the limitation of conventional formulations by offering a reduction in dose, dosing frequency, dose-dependent, side effects with enhanced efficacy. Presently nano-formulations have gained widespread application for effective and safe treatment of psoriasis. The present review primarily focuses on conventional therapeutic strategy and recent advances in lipid-based, polymer-based and metallic nano-formulations of a variety of anti-psoriatic drugs. The practicability of various nanocarrier systems including liposomes, nanostructured lipid carriers, ethosomes, solid lipid nanoparticles, nanocapsules, micelles, dendrimers, gold nanoparticles and silver nanoparticles have been discussed in detail. The review also traces related patents to exemplify the role of various nanoparticles in psoriasis treatment. In a nutshell, nano-formulations remain established as a promising modality for treating psoriasis treatment as they propose better penetration, targeted delivery, enhanced safety, and efficacy.

Utilizing the diverse features of biocompatible polymers to target drugs into the tumor/s has been a research hotspot since last decade. Such polymeric conjugates of anti-cancer drugs have proven their potential in providing sustained release of drugs with reduced systemic toxicity and improved tumor retention. Polymers like polyethylene glycol (PEG), N-(2-Hydroxypropyl) methacrylamide (HPMA), Polylactic-co-glycolic acid (PLGA), Polyamidoamine (PAMAM), and others remain exploited for their specific as well as shared characteristics in the rational delivery of anti-cancer agents. Variable nano size, attachment with tumor-specific proteins, responsiveness to stimuli and ability to deliver a wide range of molecules like drugs, antibodies and peptides are some of the achievements of polymeric nano-conjugates so far. Many such conjugates have shown potential clinically which has attracted the researchers and promoted further advancements of the technique. Apart from achievements the polymeric conjugates suffer from shortcomings like poor drug loading and chances of potential chronic-systemic toxicities. The review highlights key findings of research in recent time and advancements taking place in the field of polymeric conjugates of anti-cancer drugs along with the limitations. We have also emphasized on newer and relatively less explored applications of tumor-targeted polymeric conjugates which can add new dimensions to this technique.

Diabetes associated oxidative stress and impaired cholinergic neurotransmission causes cognitive deficits. Although phloridzin shows antioxidant- and insulin sensitizing-activities, its ameliorative potential in diabetes-induced memory dysfunction remains unexplored. In the present study, type 2 diabetes (T2D) was induced by streptozotocin (35 mg/kg, intraperitoneal) in rats on ad libitum high-fat diet. Diabetic animals were treated orally with phloridzin (10 and 20 mg/kg) for four weeks. Memory functions were evaluated by passive avoidance test (PAT) and novel object recognition (NOR) test. Brains of rats were subjected to biochemical analysis of glutathione (GSH), brain-derived neurotrophic factor (BDNF), malonaldehyde (MDA) and acetylcholinesterase (AChE). Role of cholinergic system in the effects of phloridzin was evaluated by scopolamine pre-treatment in behavioral studies. While diabetic rats showed a significant decrease in step through latency in PAT, and exploration time and discrimination index in NOR test; a substantial increase in all parameters was observed following phloridzin treatment. Phloridzin reversed abnormal levels of GSH, BDNF, MDA and AChE in the brain of diabetic animals. Moreover, in silico molecular docking study revealed that phloridzin acts as a potent agonist at M1 receptor as compared to acetylcholine. Viewed collectively, reversal of T2D-induced memory impairment by phloridzin might be attributed to upregulation of neurotrophic factors, reduced oxidative stress and increased cholinergic signaling in the brain. Therefore, phloridzin may be a promising molecule in the management of cognitive impairment comorbid with T2D.

Development of natural mosquito repellants is essential considering their safety profile unlike synthetic insecticides. Herein, novel liquid vaporizable preparations of the essential oils obtained from the leaves of weeds Lantana camara Linn (L. Camara) family Verbenaceae, and Ocimum gratissimum Linn (O. gratissimum) family Lamiaceae were developed for the evaluation of mosquitocidal and larvicidal activities against malaria vectors, Anopheles subpictus, Aedes aegypti and Culex quinquefasciatus. While mosquitocidal effect was evaluated as knockdown of mosquitoes in modified glass chamber for an exposure period of 1 h, larvicidal activity was assessed as inhibition of larval motility in petri dish at intervals of 6-, 12- and 24-hr. Combination of essential oils of L. Camara and O. gratissimum leaves prepared in ethyl alcohol at 1:5 ratio exhibited maximum synergistic mosquitocidal effect against all three test species (94–97%). This effect was comparable with that of standard 1:1 combination ratio of essential oils of Cymbopogon nardus (L.) Rendle and Eucalyptus globulus Labill. Furthermore, statistical analysis using probit regression model for determination of LC50 and LC90 revealed excellent larvicidal effect of essential oil of O. gratissimum leaves at 24-hr time-point (LC50 = 40.08 ± 1.60 ppm and LC90 = 78.035 ± 1.90 ppm). Our data suggest the lethal effects of essential oils of L. camara and O. gratissimum leaves on Anopheles subpictus, Aedes aegypti and Culex quinquefasciatus. Therefore, essential oil preparations of these weeds can be used as natural, harmless and inexpensive mosquito repellents.

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.

The effect of Ca2+ ion cross-linker on acryalamide grafted carboxymethyl xanthan gum (CMXG-g-PAAm) on the drug release was investigated. Previously, CMXG was synthesized from XG and further grafted to CMXG-g-PAAm to retard the drug release. Once the CaCl2 solution is added to CMXG-g-PAAm, Ca2+ considerably affected the drug release mechanism mainly by diffusion and erosion. In order to validate the grafted polymer, tablets were prepared using wet granulation and dry granulation methods It has been noticed that the tablets prepared by wet granulation successfully controls the release of the drug over an extended period of time. Moreover, the release profile was aligned to Korsmeyer-Peppas equation and exhibited the drug transport mechanism via diffusion and erosion.

Vincristine is a naturally occurring anticancer drug with a specific mechanism of action, given intravenously/bolus to treat various types of cancers, including breast cancer. The present studies explored the potential of thermosensitive injectable nanogel of vincristine loaded nanoparticles. In situ gel was chosen as the delivery system because it restricts the unwanted exposure in blood and other healthy tissues, thus eliminate hemolytic side effects of the drug and offer easy administration in vivo. Furthermore, non-biodegradable and cytocompatible polymeric Eudragit RSPO nanoparticles are proposed as ideal candidates for biomedical usage. The method of preparation includes two major steps—the first formation of vincristine nanoparticles with positively charged Eudragit RSPO. In the second step, these nanoparticles were suspended into a thermosensitive gel base to act as an in situ nanogel. Characterization parameters performed are size, surface charge, vincristine sulfate release behavior and mechanism, polymer-drug interaction, and encapsulation efficiency. In situ nanogel was also evaluated for gelling time, drug release, hemocompatibility and cytotoxic activity in breast cancer MCF-7 cell lines. The magnitude of size ( Furthermore, VS loaded in situ nanogels possessed less hemolytic activity than the pure drug. Hence, it can be concluded that thermo-receptive in situ nanogel of vincristine can be used to treat breast cancer cells with less hemolytic activity. Further in vivo studies are in progress to establish the effectiveness.

In the present work, an unreported graft copolymer of carboxymethyl xanthan gum and acrylamide has been synthesised by free radical polymerisation in a nitrogen atmosphere using ammonium persulphate as an initiator. The optimum reaction conditions adopted for affording maximum percentage of grafting including its grafting efficiency were obtained by varying the concentration of carboxymethyl xanthan gum from 4 to 24 g dm(-3); ammonium persulphate from 5×10(-4) to 30×10(-4)mol dm(-3); acrylamide from 0.4 to 1.2 mol dm(-3); reaction temperature from 55 to 75°C and reaction time from 30 to 90 min. The synthesised graft copolymer has been characterised by (1)H NMR, FTIR spectroscopy, X-ray diffraction measurement, thermal analysis, viscosity measurement and scanning electron microscopy. However, grafting of acrylamide onto carboxymethyl xanthan gum backbone enhanced its thermal stability. This graft copolymer might be well exploited globally as a potential carrier for drug delivery system.

Poor aqueous solubility of anticancer drug bortezomib (BTZ) still remains a major challenge in the development of a successful formulation. The dendrimeric platform can provide a better opportunity to deliver BTZ with improved solubility. BTZ encapsulated in PEGylated PAMAM dendrimers (BTZ-PEG-PAMAM) was characterized and evaluated comparatively with encapsulated and conjugated dendritic formulations. The particle size of BTZ-PEG-PAMAM was 188.6 ± 4.17 nm, with entrapment efficiency of 78.61 ± 2.91% and drug loading of 39.30 ± 1.98%. The aqueous solubility of BTZ in PAMAM-PEG conjugate was enhanced by 68.11 folds in comparison to pure drug. In vitro drug release profile was found to be sustained up to 72 h. A comparative colorimetric MTT assay against A549 and MCF-7 cancer cells resulted in maximum efficacy from BTZ-PEG-PAMAM with IC50 value 333.14 ± 15.42 and 152.60 ± 24.56 nM, respectively. Significantly higher cellular internalization was observed in FITC tagged BTZ-PEG-PAMAM. In vivo pharmacokinetic study performed on Sprague Dawley rats resulted in 8.63 folds increase in bioavailability for BTZ-PEG-PAMAM than pure drug. Pharmacokinetic parameters of BTZ-PEG-PAMAM were better and improved over BTZ and other dendritic formulations. In conclusion, the prepared formulation of BTZ-PEG-PAMAM has given significant outcome and this strategy may be further explored for better delivery of BTZ in future.

Protein and peptide delivery by the use of stimuli triggered polymers remains to be the area of interest among the scientist and innovators. In-situ forming gel for the parenteral route in the form of hydrogel and implants are being utilized for various biomedical applications. The formulation of gel depends upon factors such as temperature modulation, pH changes, the presence of ions and ultra-violet irradiation, from which drug is released in a sustained and controlled manner. Among various stimuli triggered factors, thermoresponsive is the most potential one for the delivery of protein and peptides. Poly(ethylene glycol) (PEG) based copolymers play a crucial role as a biomedical material for biomedical applications, because of its biocompatibility, biodegradability, thermosensitivity and easy controlled characters. This review, stresses on the physicochemical property, stability and compositions prospects of smart thermoresponsive polymer specifically, PEG/Poly(N-isopropylacrylamide) (PNIPAAm) based thermoresponsive injectable hydrogels, recently utilized for biomedical applications. PEG-PNIPAAm based hydrogel exhibits good gelling mechanical strength and minimizes the initial burst effect of the drug. In addition, upon changing the composition and proportion of the copolymer molecular weight and ratio, the gelling time can be reduced to a great extent providing better sol-gel transition. The hydrogel formed by the same is able to release the drug over a long duration of time, meanwhile is also biocompatible and biodegradable. Manuscript will give the new researchers an idea about the potential and benefits of PNIPAAm based thermoresponsive hydrogels for the biomedical application.

The current review emphasizes on the herbal bioenhancers which themselves do not possess inherent pharmacological activity of their own but when co-administered with Active Pharmaceutical Ingredients (API), enhances their bioavailability and efficacy. Herbal bioenhancers play a crucial role in enhancing the bioavailability and bioefficacy of different classes of drugs, such as antihypertensives, anticancer, antiviral, antitubercular and antifungal drugs at low doses. This paper highlights various natural compounds that can be utilized as an efficient bioenhancer. Several herbal compounds including piperine, quercetin, genistein, naringin, sinomenine, curcumin, and glycyrrhizin have demonstrated capability to improve the pharmacokinetic parameters of several potent API. This article also focuses on various United States patents on herbal bioenhancers, which has proved to be beneficial in improving oral absorption of nutraceuticals like vitamins, minerals, amino acids and certain herbal compounds. The present paper also describes proposed mechanism of action, which mainly includes absorption process, drug metabolism, and action on drug target. The herbal bioenhancers are easily available, safe, free from side effects, minimizes drug toxicity, shortens the duration of treatment, lowers the drug resistance problems and minimizes the cost of treatment. Inspite of the fact that herbal bioenhancers provide an innovative concept for enhancing the bioavailability of several potent drugs, there are numerous bioenhancers of herbal origin that are yet to be explored in several vital areas. These bioenhancers must also be implied to enhance the bioavailability and bioefficacy through routes other than the oral route of drug delivery. There is a vast array of unexploited plants which can be investigated for their drug bioenhancing potency. The toxicity profiles of these herbal bioenhancers must not be overlooked. Researches must be carried out to solve these issues and to deliver a safe and effective dose of drugs to attain desired pharmacological response.

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.

Several methods and techniques are potentially useful for the preparation of microparticles in the field of controlled drug delivery. The type and the size of the microparticles, the entrapment, release characteristics and stability of drug in microparticles in the formulations are dependent on the method used. One of the most common methods of preparing microparticles is the single emulsion technique. Poorly soluble, lipophilic drugs are successfully retained within the microparticles prepared by this method. However, the encapsulation of highly water soluble compounds including protein and peptides presents formidable challenges to the researchers. The successful encapsulation of such compounds requires high drug loading in the microparticles, prevention of protein and peptide degradation by the encapsulation method involved and predictable release, both rate and extent, of the drug compound from the microparticles. The above mentioned problems can be overcome by using the double emulsion technique, alternatively called as multiple emulsion technique. Aiming to achieve this various techniques have been examined to prepare stable formulations utilizing w/o/w, s/o/w, w/o/o, and s/o/o type double emulsion methods. This article reviews the current state of the art in double emulsion based technologies for the preparation of microparticles including the investigation of various classes of substances that are pharmaceutically and biopharmaceutically active.

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.