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Abstract: Central nervous system (CNS) disorders account for boundless socioeconomic burdens with devastating effects among the population, especially the elderly. The major symptoms of these disorders are neurodegeneration, neuroinflammation, and cognitive dysfunction caused by inherited genetic mutations or by genetic and epigenetic changes due to injury, environmental factors, and disease-related events. Currently available clinical treatments for CNS diseases, i.e., Alzheimer’s disease, Parkinson’s disease, stroke, and brain tumor, have significant side effects and are largely unable to halt the clinical progression. So gene therapy displays a new paradigm in the treatment of these disorders with some modalities, varying from the suppression of endogenous genes to the expression of exogenous genes. Both viral and non-viral vectors are commonly used for gene therapy. Viral vectors are quite effective but associated with severe side effects, like immunogenicity and carcinogenicity, and poor target cell specificity. Thus, non-viral vectors, mainly nanotherapeutics like nanoparticles (NPs), turn out to be a realistic approach in gene therapy, achieving higher efficacy. NPs demonstrate a new avenue in pharmacotherapy for the delivery of drugs or genes to their selective cells or tissue, thus providing concentrated and constant drug delivery to targeted tissues, minimizing systemic toxicity and side effects. The current review will emphasize the role of NPs in mediating gene therapy for CNS disorders treatment. Moreover, the challenges and perspectives of NPs in gene therapy will be summarized.

Background: Leiomyoma is the commonest benign smooth muscle tumor of uterus. It also occur in other organs like gall bladder,skin, gasterointestinal tract etc. Leiomyosarcoma is a rare malignant counter part of leiomyoma.Objective: To see the frequency of histopathological variants of leiomyomas in uterine specimens in Southern District ofKhyber Pakhtunkhwa Pakistan.Material and Methods: This descriptive study was conducted in Department of Pathology, Bannu Medical College Bannu incollaboration with Government and Private Hospitals of the Southern District of KPK. The duration of study was seven years fromJanuary 2011 to December 2017. A total of 210 specimen of leiomyoma were included in this study. Inclusion criteria was allbiopsies of uterine leiomyomas of any age. Exclusion criteria wa autolysed and insufficient biopsy specimen. All biopsies werefixed over night in 10% buffered formalin, processed for histopathological slides preparation. Finally slides were prepared, labeledand reported by Histopathologist. . All the data was analysed in Statistical Package for Social Sciences (SPSS) version 20 forfrequency with percentages and mean with standard deviation.Results: In this study of 210 leiomyoma cases, the age range was from 25- 65 years. The commonest age group was 36-45 yearsfollowed by 25-35 years. The frequency of leiomyoma was 21.5% amongst the total uterine biopsy specimen. Histologically theusual leiomyoma was comprising of 176(83.80%) followed by hyalinised leiomyoma 11 (5.23%), myxoid leiomyoma 09(4.28%),lipoleiomyoma 05 (2.38%), cellular leiomyoma 04 (1.90%), shwannian leiomyoma 03 (1.42%) and one each of symplastic andangioleiomyoma 01(0.47%).Conclusin: Leiomyoma which is the commonest benign smooth muscle tumor of uterus have a number of histological variants. Inthis study usuall leiomyoma was the commonest variant followed by hyalinized leiomyoma, myxoid leiomyoma and lipoleiomyoma.It is important to separate various types of leiomyoma on histology to avoid confusion of misdiagnosis.Key WordsS: Histopathology. Fibroids. Leiomyoma variants. Hysterectomy. Myomectomy.

Background: Neuropsychiatric diseases primarily characterized by dementia stand third in the global list of diseases causing disability. The poor water solubility, erratic oral absorption, low bioavailability, poor intestinal absorption, and the impeding action of the blood-brain barrier (BBB) are the major factors limiting the therapeutic feasibility of the antipsychotics. Only a small percentage of antipsychotics reaches the therapeutic target site, which warrants administration of high doses, consequently leading to unwanted side-effects. Hence the main struggle for the effective treatment of neuropsychiatric diseases occurs “at the gates” of the brain, which can be mitigated with the use of a nanotechnology-based platform. Methods: The goal of this review is to undertake a comprehensive study about the role of lipid nanoformulations in facilitating the delivery of antipsychotics across BBB along with the available in vitro and in vivo evidence. Results: Lipid nanoformulations have attained great popularity for the delivery of therapeutics into the brain. Their nanosize helps in overcoming the biological barriers, thereby providing easy BBB translocation of the drugs. Besides, they offer numerous advantages like controlled and targeted drug release, minimizing drug efflux, long storage stability, augmented bioavailability, and reduced adverse drug effects to attain an optimal therapeutic drug concentration in the brain. Moreover, employing alternative routes of administration has also shown promising results. Conclusion: Thus, it can be concluded that the lipid nanoformulations bear immense potential in overcoming the challenges associated with the treatment of neuropsychiatric disorders. However, the area warrants further clinical studies to ensure their commercialization, which could revolutionize the treatment of neuropsychiatric diseases in the coming decades.

NeuroAIDS, a disease incorporating both infectious and neurodegenerative pathways, is still a formidable challenge for the researchers to deal with. The primary concern for the treatment of neuroAIDS still remains the inaccessibility of the viral reservoir, making it indispensable for novel techniques to be continuously innovated. Since the brain serves as a reservoir for viral replication, it is pragmatic and a prerequisite to overcome the related barriers in order to improve the drug delivery to the brain. The current treatment ideology is based on the combinatorial approach of a mocktail of antiretroviral drugs. However, complete eradication of the disease could not be achieved. Thereby the arena of gene-based cellular delivery is trending and has created a niche for itself in the present scenario. To establish the supremacy of gene delivery, it is advisable to have a better understanding of the molecular mechanism involved in the due process. The mechanism associated with the activity of the anti-HIV gene lies in their intrinsic property to impart resistance to the HIV infection by targeting the viral entry channels. This review principally emphasizes on different types of gene therapies explored so far for the management of AIDS and its associated neurological conditions. Therefore it could rightly be said that we are at the crossroad where the need of the hour is to develop novel strategies for curbing AIDS and its associated neurological conditions.

The neuropsychiatric illnesses have been enigmatic, with no effective treatment to date. The complexity and heterogeneity of psychiatric disorders are daunting for the development of novel treatment modalities. The conventional treatment approaches are less effective and are associated with several side effects, thus creating the need for the development of more innovative strategies. Since psychiatric disorders are known to exhibit genetic linkage, gene therapy has created an interest among the researchers worldwide. The delivery of nucleic acids is a complex process requiring the transport of genetic material across various intracellular and extracellular barriers to reach the target cells eliciting the transfection process. Therefore, the identification or development of the delivery system for nucleic acid delivery still remains the challenge. Viral vectors are quite effective but are associated with toxicity and side effects. With the rapid advancement in the field of nanotechnology, nanosized materials were identified to be the perfect candidate for nonviral vectors in gene delivery. The biggest advantage of nanoparticles is that their surface can be engineered in many possible ways to deliver the drugs directly to the target site. Although gene therapy has already been established as an innovative treatment modality for several neurological diseases, its use in psychiatry still warrants more investigations for its translation into clinical use. The present manuscript discusses the prospects of gene therapy in psychiatric disorders, their benefits, and pitfalls. The review embarks upon the importance of nanoparticle-based gene therapy for effective management of psychiatric disorders.

Tuberculosis (TB) classified as one of the most fatal contagious diseases is of prime concern globally. Mycobacterium tuberculosis is the causative agent that ingresses within the host cells. The approved conventional regimen, though the only viable option available, is unfavorably impacting the quality of life of the affected individual. Despite newer antibiotics gaining light, there is an unending demand for more therapeutic alternatives. Therefore, substantial continuous endeavors are been undertaken to come up with novel strategies to curb the disease, the stepping stone being nanotechnology. This approach is instrumental in overcoming the anomalies associated with conventional therapy owing to their intriguing attributes and leads to optimization of the therapeutic effect to a certain extent. This review focusses on the different types of nanocarrier systems that are being currently explored by the researchers for the delivery of anti-tubercular drugs, the outcomes achieved by them, and their prospects. Graphical abstract.

Purpose: The objective of the research undertaken was to develop the Riluzole (RIZ) nanoparticles drug delivery system using Transferrin (Tf) as a ligand in the brain.Method: RIZ-loaded chitosan na...

Present research focuses on formulating the empagliflozin (EMPA) loaded chitosan nanoparticles (CS Nps) using quality by design approach to overcome its innate adverse effects and enhance therapeutic prospects. Box- Behnken design (BBD) suggested quadratic model for fabricating EMPA Nps, by ionic gelation method, showing significant effect of independent variables on responses. The particle size and polydispersity index (PDI) for formulated EMPA loaded CS Nps was 152.4 ± 0.84 nm and 0.245 ± 0.005, respectively. The % entrapment efficiency and loading capacity of EMPA Nps was 83.8 ± 0.002% and 42.9 ± 0.03 %. Surface morphology of Nps using TEM, DSC and FTIR spectra of pure drug and formulated Nps were studied for further characterization. In vitro release of EMPA CS Nps showed better release profile than pure EMPA solution when compared in 2 different buffers namely; Phosphate buffer pH 7.4 (85.19 ± 4.22 %) and HCl buffer pH 1.2 (86.68 ± 7.33%). Permeability coefficient enhanced by 6.2-fold in case of EMPA CS Nps attributing to increase in intestinal uptake owing to small particle size. The study of pharmacokinetic parameters showed increase in plasma concentration and elimination half -life of EMPA Nps when compared to EMPA suggesting better distribution of drug inside the systemic circulation. The stability study conducted for 90 days showed no variations in the physical stability of Nps. The application of quality by design approach for EMPA loaded CS NPs showed improved permeation, drug release and better pharmacokinetic profile proposing CS as a promising carrier of EMPA for the better efficacy, leading to prospective clinical fate.

Intranasal nanostructured lipid carrier (NLC) of lurasidone hydrochloride (LRD) for brain delivery was prepared by the solvent evaporation method. The effects of independent variables, X1-lipid concentration, X-2 surfactant, and X-3 sonication times on dependent variables, Y1-particle size, Y-2 polydispersity index, and Y-3% entrapment efficiency were determined using Box-Behnken design. Optimized LRD-NLC was selected from the Box-Behnken design and evaluated for their morphological, physiological, nasal diffusion, and in vivo distribution in the brain after intranasal administration. Particle size, polydispersity index, and entrapment efficiency of optimized LRD-NLC were found to be 207.4 ± 1.5 nm, 0.392 ± 0.15, and 92.12 ± 1.0%, respectively. Transmission electron microscopy and scanning electron microscopy was used to determine the particle size and surface morphology of LRD-NLC. The prepared LRD-NLC follows biphasic in vitro drug release. Prepared NLC showed a 2-fold increase in LRD concentration in the brain when compared with the drug solution following intranasal administration. Results showed that intranasal route can be a good and efficient approach for delivering the drug directly to the brain and enhancing the drug efficacy in the brain for the management of schizophrenia and a good alternative to oral drug delivery.

Objective: This study aimed to see the clinical presentation and histological pattern of various head and neck lesions.Materials and Methods: This descriptive study was conducted in the Department of Pathology, Bannu Medical College in association with the Department of Surgery and ENT, Khalifa Gul Nawaz Teaching Hospital, Bannu. A total of 184 cases of head and neck lesions biopsy were subjected to histopathological diagnosis. Patients' age, gender, anatomical location, and other relevant necessary clinical findings were recorded on an already designed proforma. All biopsies were received in 10% buffered formalin, fixed overnight, and processed for histopathological examination and diagnosis. Inclusion criteria were patients with head and neck lesions including skin, salivary gland, lymph node, and oral cavity of any age and gender. Exclusion criteria were thyroid, nasal cavity lesions, autolysed, and insufficient biopsy specimen. Results: In this study, the mean age was 28.58 ± 17.34 years, and the age range was from 10 to 80 years. The male-to-female ratio was 1.3:1. The most common age group was 36-45 years followed by 46-55 years and 26-35 years etc. The most common inflammatory lesion was granulomatous lymphadenitis 14.67% followed by reactive lymphoid hyperplasia 9.23%. Common benign lesions were pleomorphic adenoma 5.97% followed by lipoma and hemangioma 3.80% and 3.26% respectively. Amongst malignant lesions basal cell carcinoma 23.91% of the face was the commonest lesion followed by squamous cell carcinoma 22.28% of the oral cavity. Conclusion: This study show spectrum of lesions from inflammatory to benign and malignant, occurring in the head and neck region. Malignant lesions are more common as compared to benign and inflammatory lesions, basal cell carcinoma of the skin is the commonest malignant lesion followed by squamous cell carcinoma of the skin and oral cavity.

The research presented aims at developing Ropinirole hydrochloride (RHCl) nanoemulsion (NE) with nigella oil for Parkinson's disease (PD). In silico study was done to explore interactions of ropinirole and thymoquinone at receptor site (TNF-α and NFK-β). Ropinirole and Thymoquinone forms a hydrogen bond with residue Arginine 201 and residue Arginine 253 with a bond length of 1.89 A and 2.30 A at the NF-κβ receptor. NE was optimized using Central Composite Rotatable Design (CCRD). The globule size of chitosan coated NE, Polydispersity index (PDI) and zeta potential were 183.7 ± 5.2 nm, 0.263 ± 0.005, and 24.9 mV respectively. NE exhibited 85.28% transmittance showing the formulation was clear and transparent. TEM showed that NE had spherical globules with no aggregation. The formulation had a stable pH value of 5.8 ± 0.18. In vitro release and permeation studies exhibited 2 folds and 3.4 folds enhancement when compared with the drug suspension. Neurobehavioral activity and biochemical parameters corroborated well with the pharmacokinetic results. Histopathological study and immunohistochemical analysis were performed to get better picture of 6-OHDA induced toxicity and reversal of PD symptoms. Thus, the NE tailored is a promising synergistic approach yielding enticing outcomes for better management of PD related symptoms.

The present research encompasses a quality by design approach for fabricating lipid architectonics (LA) of an antiretroviral drug (Elvitegravir: EVR) to overcome inherent challenges of EVR to curtail its bioavailability issues. Comparative development strategy employing Box–Behnken design was undertaken between high-pressure homogenization technique and melt emulsification followed by probe sonication method, wherein the later was selected for engineering the EVR-LA. Particle size, entrapment efficiency and drug loading for EVR-LA were 84.6 ± 2.3 nm, 90.7 ± 1.8% and 8.9 ± 0.7% respectively. In vitro release studies established the supremacy of EVR-LA when compared with drug suspension (EVR-DS) by having a cumulative drug release of 96.89 ± 2.5% in pH 1.2, 89.84 ± 2.4% in pH 6.8 and 86.64 ± 2.5% in pH 7.4. Gut permeation studies revealed 19-fold increment in permeation by EVR-LA attributable to intrinsic permeation enhancing and efflux protein inhibitory activity of the lipids and surfactants incorporated. The result was validated by confocal study which exhibited enhanced permeation by EVR-LA. Dissolution study, conducted in fasted state simulated intestinal fluid (FaSSIF) and fed state simulated intestinal fluid (FeSSIF) media to ascertain the effect of food, demonstrated boosted absorption from FeSSIF media. Stability study was conducted in SGF pH 1.2, FaSSIF and FeSSIF media. The lipolysis study, conducted to determine in vivo fate of EVR, revealed 27-fold increment in solubilization potential from EVR-LA (72.43 ± 2.6%). Thus, EVR-LA exhibited remarkable in vitro results by improving gut permeation and solubilization fate along with enhanced lymphatic uptake, thereby leading to prospective in vivo fate.

Background: Human immunodeficiency virus (HIV)/AIDS is one of the principal concerns contributing to the global burden and the accompanying deleterious outcomes could not be left unattended. Despite significant advances and innovative research being conducted throughout the globe in order to improve the therapeutic profile of conventionally available antiretroviral (ARV) drugs in the eradication of HIV virus reservoirs, its penetration across the blood-brain barrier (BBB) is still a formidable mission. This makes the central nervous system a dominant and vulnerable site for virus propagation, which ultimately affects the therapeutic potential of the drug administered. Therefore there is an upsurge in the prerequisite of novel technologies to come into play, paving the way for nanotechnology. Methods: This review primarily provides a comprehensive outline and emphasizes on the nanotechnological techniques employed for the delivery of ARV drugs and their stupendous advantages in overcoming the hurdles associated with the same. Results: The nanotechnological approach bears the potential of site-specific delivery across the BBB via targeting explicit transport processes and provides a sustained release mechanism. Furthermore, different routes of administration explored have also yielded beneficial outcomes for the delivery of ARV drugs. Conclusion: The futuristic holistic nanotechnology methods, however, should focus on increasing drug trafficking and permeability across the BBB to ameliorate the therapeutic effect of ARV drugs. Additionally, the domain warrants clinical studies to be undertaken to make the technology commercially viable and a success to deal with the problems of the treatment strategy.

Saffron reproduces vegetatively; hence, improvement through breeding is difficult. From the last few decades, the tissue culture and genetic engineering techniques are being exploited for propagation and genetic improvement of vegetatively propagated plants. In the present study, the authors cultured stigmas, tepals, and anthers as explants on different nutrient media supplemented with various concentrations of growth regulators to standardize the media composition for the development of stigmas under in vitro conditions. Best response with respect to the callus formation was observed with anther explants (78.33%) on Murashige and Skoog (MS) medium supplemented with 19.8 µM BAP and 43.2 µM NAA (Z1) followed by moderate callusing with tepals (54.66%) and stigmas (43%) on the same medium. Callusing on MS medium added with 15.4 µM BAP and 54 µM NAA (Z2) was also moderate with all explants. With respect to the development of stigma and stigma-like structures (SLS), the best responses (46.33%) were observed with stigmas on MS medium added with 19.8 µM BAP and 14.6 µM NAA (A1) followed by the formation of only SLS (43%) on Z1 medium. Proper stigma development in Kashmir saffron was reported first time in the present study. The SLS and stigma development were indirect, having an intermediate phase of callus formation. Explants like anther and tepal after callusing did not show further development. However, callus obtained from tepals showed the formation of some leaf-like structures.

The drug delivery across the brain has always been problematic due to the tight junction present namely the blood brain barrier (BBB). BBB only allows selected pharmaceutical drugs to get across it and reach the brain via lipid free diffusion process and exert their therapeutic effect. This leads to the decrease in drug accessibility to brain. More recently, various approaches were employed to allow larger molecules to cross BBB by reengineering them and conjugating them with ligands which could facilitate their entry across BBB. Therefore literature was explicitly exploited to deduce various ligands employed to enhance the drug delivery across brain via transcytosis. As per established literature, there are evidences that ligand conjugated drug formulations have substantially improved brain uptake. The review presents numerous ligands employed along with the receptor targeted to improve drug uptake by the brain, its anticipated effects and the outcome derived.

Photodynamic therapy (PDT) is an important tool for the treatment of various cutaneous malignant and non-malignant diseases. This therapy involves the application of a photosensitizer to the affected area which is followed by illumination with the light of a particular wavelength resulting in the death of cancerous cells. This review encompasses a brief description of the mechanism of photodynamic therapy and different photosensitizers used clinically. However, the major obstacle with a majority of photosensitizers is its limited bioavailability and long-term photosensitivity which limits its use. To overcome these limitations different nanocarriers systems has been developed and studied for their efficacy in PDT, which forms the focal point of the review.

Introduction: Intranasal drug delivery is a largely unexplored, promising approach for the treatment of various neurological disorders. However, due to the challenging constraints available in the pathway of nose-to-brain delivery, finding an effective treatment for Parkinsonism is still an impending mission for research workers. This warrants development of novel treatment alternatives for Parkinson's disease (PD). Intranasal delivery of mucoadhesive nanocarriers is one such novel approach which might help in curbing the glitches associated with the currently available therapy.Areas covered: This review summarizes the evidences supporting nose-to-brain delivery of polymer-based mucoadhesive nanocarriers for the treatment of PD. A concise insight into the lipid-based mucoadhesive nanocarriers has also been presented. The recent researches have been compiled pertaining to the use of mucoadhesive nanocarrriers for improving the treatment outcomes of PD via intranasal drug delivery.Expert opinion: Although the use of nanocarrier-based strategies for site-specific delivery via intranasal route has proven effective, the magnitude of improvement remains moderate resulting in limited translation from industry to the market. Comprehensive understanding of the mucoadhesive polymer, its characteristics and mechanisms involved for an effective nose-to-brain uptake of the drug is a promising avenue to develop novel formulations for effective management of Parkinson disease.

Objective.The aim of the present study was to improve bioavailability of an important antiretroviral drug, Darunavir (DRV), which has low water solubility and poor intestinal absorption through solid dispersion (SD) approach incorporating polymer with P-glycoprotein inhibitory potential.Methods.A statistical approach where design of experiment (DoE) was used to prepare SD of DRV with incorporation of P-glycoprotein inhibitors. Using DoE, different methods of preparation, like melt, solvent evaporation, and spray drying method, utilizing carriers like Kolliphor TPGS and Soluplus were evaluated. The optimized SD was characterized by DSC, FTIR, XRD, and SEM and further evaluated for enhancement in absorption using everted gut sac model, effect of food on absorption of DRV, andin vivoprospect.Results and Discussion.DSC, FTIR, XRD, and SEM confirmed the amorphicity of drug in SD. Oral bioavailability studies revealed better absorption of DRV when given with food. Absorption studies andin vivostudy findings demonstrated great potential of Kolliphor TPGS as P-glycoprotein inhibitor for increasing intestinal absorption and thus bioavailability of DRV.Conclusion.It is concluded that SD of DRV with the incorporation of Kolliphor TPGS was potential and promising approach in increasing bioavailability of DRV as well as minimizing its extrusion via P-glycoprotein efflux transporters.

The present research work involves Quality by Design (QbD)-based fabrication of lipid nanoconstructs (LNC) of paliperidone (PPD) bearing superior biopharmaceutical attributes.LNC of paliperidone was prepared by melt emulsification-probe sonication and high-pressure homogenization method followed by optimization using QbD approach. Preparing LNC by both these methods will give the benefit of identifying the best optimized formulation which will be further evaluated for in vitro studies.The best optimized formulation was obtained using melt emulsification-probe sonication technique with small particle size (86.35 nm), high entrapment efficiency (90.07 %), and high loading capacity (8.49 %). The drug release from LNC was found to be 5, 8, and 9-folds greater than drug suspension in pH 1.2, 6.8, and 7.4 respectively (p0.001). Stability studies of LNC in simulated gastric fluid pH 1.2 and fasted state simulated intestinal fluid depicted no alteration in particle size and polydispersity index of LNC but were found to increase in fed state simulated intestinal fluid. The drug permeability through rat intestine for LNC was found to be approximately 6-folds (p0.05) greater as compared to the drug suspension which was further confirmed by confocal microscopy. The in vitro lipolysis study presented significantly highest solubilization (p0.001) in the aqueous phase thereby anticipating higher in vivo absorption.Thus, it was concluded that LNC bears the knack of improving the solubilization and permeation potential of an otherwise hydrophobic drug, paliperidone."

Terbinafine hydrochloride, although one of the prominent antifungal agents, suffers from low drug permeation owing to its hydrophobic nature. The approach of nanosponge formulation may thus help to resolve this concern. Thus, the present research was envisioned to fabricate the nanosponge hydrogel of terbinafine hydrochloride for topical delivery since nanosponge augments the skin retentivity of the drug. The optimized formulation was obtained using Box Behnken Design. The dependent and independent process parameters were also determined wherein polyvinyl alcohol (%), ethylcellulose (%), and tween 80 (%) were taken as independent process parameters and particle size, polydispersity index (PDI), and entrapment efficiency (EE) were the dependent parameters. The nanosponge was then incorporated into the hydrogel and characterized. In-vitro drug release from the hydrogel was 90.20 &plusmn, 0.1% which was higher than the drug suspension and marketed formulation. In vitro permeation potential of the developed formulation through rat skin showed a flux of 0.594 &plusmn, 0.22 &micro, g/cm2/h while the permeability coefficient was 0.059 &plusmn, 0.022 cm/s. Nanosponge hydrogel was evaluated for non-irritancy and antifungal activity against C. albicans and T. rubrum confirming the substantial outcome. Tape stripping studies exhibited ten times stripping off the skin quantified 85.6 &plusmn, 0.21 &mu, g/cm2. The confocal analysis justified the permeation potential of the prepared hydrogel. The mean erythemal score was 0.0, confirming that the prepared hydrogel did not cause erythema or oedema. Therefore, based on results obtained, nanosponge hydrogel formulation is a potential carrier for efficient topical delivery of terbinafine hydrochloride.

With an aim to primarily focus on selection and identification of target-modulated candidates, there has been a dramatic rise in drug candidates belonging to BCS Class II and IV. These were more potent and efficacious but were accompanied by problems of poor water solubility, poor permeability, small absorption window, and being the substrates of efflux transporters, have brought major drawbacks in poor in vivo dissolution and consequently poor bioavailability. Among the various technologies to resolve this issue, amorphous solid dispersions (ASDs) serve as an attractive alternative. They utilize their potential of altering molecular arrangement and maintaining a supersaturated state, thus rendering the drug into a high-energy amorphous state, and further improving its in vivo prospects. The ASDs have been prepared using both synthetic and natural polymers with the latter outweighing the former in various aspects, the most crucial being that it is devoid of side effects and toxicity. The polysaccharides are such natural polymers, widely utilized as carriers in ASDs. In the current chapter, polysaccharide carriers are critically reviewed and their therapeutic significance about solubility and bioavailability enhancement is highlighted in the light of previous research.

Osteoarthritis (OA), a progressive degenerative joint disease, is one of the most prevalent and disabling chronic diseases affecting elderly people, particularly women. Loss of ovarian function leading to estrogen deficiency has been linked to the increasing prevalence of OA in postmenopausal women. It is the most common form of arthritis encountered in developed countries (15%) and is a disease of concern because it affects the mobility of individuals and their quality of life. Although there is no cure for OA, nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed to alleviate pain by reducing ongoing inflammatory processes. These NSAIDs act by blocking prostaglandin synthesis but are unable to influence other mediators of inflammation such as leukotrienes and complement pathways. In addition, numerous disadvantages are associated with consumption of NSAIDs, such as gastrointestinal and renal complications. Therefore, there is a high need for better and safer alternatives that may lead to a shift in the paradigm from NSAIDs to natural products. This is because of better tolerance and decreased adverse drug reactions for these natural agents. They offer great possibilities in identifying bioactive lead compounds and their further development into drugs for treating inflammatory diseases. This chapter deals with such natural products, which can prove to be a boon in managing OA. In addition, scientific evidence supporting the efficacy of these natural products is discussed.

Leprosy, also known as Hansen’s disease, is a chronic infectious disease primarily producing skin lesions and nerve damage and is caused by Mycobacterium leprae bacillus. In terms of epidemiology, India bears 60% of the global cases of leprosy, followed by Brazil and Indonesia. Although there are many chemically defined moieties currently being used as antileprotic agents commercially, they are associated with numerous adverse side effects. However, there are a vast number of naturally occurring agents that are not much explored and hence, not prescribed for the treatment of leprosy. These agents offer the advantage of low toxicity. Thus they could be a boon in the management of leprosy. The present chapter is an attempt to encompass the detailed descriptions of natural agents, both in plants and in animals, possessing antileprotic properties. The scientific evidence backing the use of such agents in leprosy is also discussed in this chapter.

The therapeutic functionality of innumerable antiretroviral drugs is supposedly obscured owing to their low metabolic stability in the gastrointestinal tract and poor solubilization property leading to poor oral bioavailability. Dictated by such needs, lipid-based formulations could be tailored using nanotechnology which would be instrumental in ameliorating the attributes of such drugs. The stupendous advantages which lipid nanocarriers offer including improved drug stability and peroral bioavailability coupled with sustained drug release profile and feasibility to incorporate wide array of drugs makes it a potential candidate for pharmaceutical formulations. Furthermore, they also impart targeted drug delivery thereby widening their arena for use. Therefore, the review will encompass the details pertaining to numerous lipid nanocarriers such as nanoemulsion, solid lipid nanoparticle, nanostructured lipid carriers, and so on. These nanocarriers bear the prospective of improving the mucosal adhesion property of the drugs which ultimately upgrades its pharmacokinetic profile. The biodegradable and physiological nature of the lipid excipients used in the formulation is the key parameter and advocates for their safe use. Nevertheless, these lipid-based nanocarriers are amenable to alterations which could be rightly achieved by changing the excipients used or by modifying the process parameters. Thus, the review will systematically envisage the impending benefits and future perspectives of different lipid nanocarriers used in oral delivery of antiretroviral drugs.

International audience; Network intrusion detection (NID) is a complex classification problem. In this paper, we combine classification with recent and scalable nonlinear dimensionality reduction (NLDR) methods. Classification and DR are not necessarily adversarial, provided adequate cluster magnification occurring in NLDR methods like $t$-SNE: DR mitigates the curse of dimensionality, while cluster magnification can maintain class separability. We demonstrate experimentally the effectiveness of the approach by analyzing and comparing results on the big KDD99 dataset, using both NLDR quality assessment and classification rate for SVMs and random forests. Since data involves features of mixed types (numerical and categorical), the use of Gower's similarity coefficient as metric further improves the results over the classical similarity metric.

The treatment of acne warrants development of formulation aiming to enhance topical delivery with minimum systemic absorption. The aim of present study was to develop, optimize and characterize clindamycin phosphate-loaded nanostructured lipid carriers (CP-NLC) gel for enhanced topical delivery. CP-NLC was prepared using melt emulsification comibined with sonication technique using oleic acid (liquid lipid), precirol ATO5 (solid lipid), and tween 80 (surfactant). The optimized formulation attained using Box-Behnken statistical design exhibited particle size of 136 ± 0.11 nm, narrow PDI (0.256 ± 0.10), and high entrapment efficiency and high drug loading. TEM and SEM studies confirmed the spherical nature of the particles. Further, CP-NLC was loaded into Carbopol®940 gel and 1% concentration was evaluated for in vitro studies. The drug release from CP-NLC gel was 1.5-fold greater than from marketed formulation Clindac A®. The cumulative drug permeated through the skin was also found to be higher for CP-NLC gel (1.6-fold) than Clindac A® gel. The skin retention study, tape stripping technique and confocal laser scanning microscopy demonstrated enhanced skin retention and depth of permeation for CP-NLC gel. Therefore, formulating NLC for topical delivery of CP will render many benefits over marketed formulation thus proving as a promising carrier in the treatment of acne.