Revolutionizing Neurological Disorder Treatment: Integrating Innovations in Pharmaceutical Interventions and Advanced Therapeutic Technologies.

Neurological disorders impose a significant burden on individuals, leading to disabilities and a reduced quality of life. However, recent years have witnessed remarkable advancements in pharmaceutical interventions aimed at treating these disorders. This review article aims to provide an overview of the latest innovations and breakthroughs in neurological disorder treatment, with a specific focus on key therapeutic areas such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy, and stroke. This review explores emerging trends in drug development, including the identification of novel therapeutic targets, the development of innovative drug delivery systems, and the application of personalized medicine approaches. Furthermore, it highlights the integration of advanced therapeutic technologies such as gene therapy, optogenetics, and neurostimulation techniques. These technologies hold promise for precise modulation of neural circuits, restoration of neuronal function, and even disease modification. While these advancements offer hopeful prospects for more effective and tailored treatments, challenges such as the need for improved diagnostic tools, identification of new targets for intervention, and optimization of drug delivery methods remain. By addressing these challenges and continuing to invest in research and collaboration, we can revolutionize the treatment of neurological disorders and significantly enhance the lives of those affected by these conditions.

Aurothioglucose encapsulated nanoparticles fostered neuroprotection in streptozotocin-induced Alzheimer's disease.

Alzherimer's disease (AD) is an age-dependent ubiquitous ailment worldwide with limited therapies that only alleviate the symptoms of AD but do not cure them entirely because of the restricted blood-brain barrier passage of the drug. Hence with new advanced technology, nanoparticles can offer an opportunity as the active candidate to overcome the above limitations. Aurothioglucose, a synthetic glucose derivative of the gold compound, has been clinically proven to be an effective anti-inflammatory drug for rheumatic arthritis. Recently, several scientific groups have developed gold nanoparticle preparations and tested them for the treatment of dementia. This study was planned to prepare the PLGA nanoparticles of aurothioglucose (ATG) and check the neuroprotective potential against STZ-induced AD in rats. The nanoparticles were prepared using the double emulsion solvent evaporation method and characterized for various parameters such as drug-excipient interaction, particle size, zeta potential, and morphology. Then, rats were injected STZ (3 mg/kg/i.c.v., days 1 and 3) and ATG (5 and 10 mg/kg/s.c.), ATG NPs (2.5 and 5 mg/kg/s.c.) and donepezil (2 mg/kg/p.o) from 15th to 29th day. Behavior parameters were performed using an actophotometer, MWM, and ORT. On the 30th day, all the animals were sacrificed, and the brains were isolated for estimating biochemical, neurochemical, and proinflammatory markers. It was observed that ATG NPs significantly restored all behavior and neurotransmitter alterations caused by STZ. Also, it increased antioxidant levels and decreased inflammatory cytokines significantly, then ATG alone. Thus, the study suggests that ATG loaded PLGA NPs could be used as a novel therapeutic strategy to slow the process of AD.

Dextran-based Drug Delivery Approaches for Lung Diseases: A Review.

Respiratory disorders, such as tuberculosis, cystic fibrosis, chronic obstructive pulmonary disease, asthma, lung cancer, and pulmonary inflammation, are among the most prevalent ailments in today's world. Dextran, an exopolysaccharide formed by Leuconostoc mesenteroides (slimeproducing bacteria), and its derivatives are investigated for several therapeutic utilities. Dextranbased drug delivery system can become an innovative strategy in the treatment of several respiratory ailments as it offers numerous advantages, such as mucolytic action, airway hydration, antiinflammatory properties, and radioprotective effect as compared to other polysaccharides. Being biocompatible, flexible hydrophilic nature, biodegradable, tasteless, odourless, non-mutagenic, watersoluble and non-toxic edible polymer, dextran-based drug delivery systems have been explored for a wide range of therapeutic applications, especially in lungs and respiratory diseases. The present article comprehensively discusses various derivatives of dextran with their attributes to be considered for drug delivery and extensive therapeutic benefits, with a special emphasis on the armamentarium of dextran-based formulations for the treatment of respiratory disorders and associated pathological conditions. The information provided will act as a platform for formulation scientists as important considerations in designing therapeutic approaches for lung and respiratory diseases. With an emphasis on lung illnesses, this article will offer an in-depth understanding of dextran-based delivery systems in respiratory illnesses.

Delivery of gene editing therapeutics.

For the past decades, gene editing demonstrated the potential to attenuate each of the root causes of genetic, infectious, immune, cancerous, and degenerative disorders. More recently, Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-associated protein 9 (CRISPR-Cas9) editing proved effective for editing genomic, cancerous, or microbial DNA to limit disease onset or spread. However, the strategies to deliver CRISPR-Cas9 cargos and elicit protective immune responses requires safe delivery to disease targeted cells and tissues. While viral vector-based systems and viral particles demonstrate high efficiency and stable transgene expression, each are limited in their packaging capacities and secondary untoward immune responses. In contrast, the nonviral vector lipid nanoparticles were successfully used for as vaccine and therapeutic deliverables. Herein, we highlight each available gene delivery systems for treating and preventing a broad range of infectious, inflammatory, genetic, and degenerative diseases. STATEMENT OF SIGNIFICANCE: CRISPR-Cas9 gene editing for disease treatment and prevention is an emerging field that can change the outcome of many chronic debilitating disorders.

Potential of Phytomolecules in Alliance with Nanotechnology to Surmount the Limitations of Current Treatment Options in the Management of Osteoarthritis.

Osteoarthritis (OA), a chronic degenerative musculoskeletal disorder, progressively increases with age. It is characterized by progressive loss of hyaline cartilage followed by subchondral bone remodeling and inflammaging. To counteract the inflammation, synovium releases various inflammatory and immune mediators along with metabolic intermediates, which further worsens the condition. However, even after recognizing the key molecular and cellular factors involved in the progression of OA, only disease-modifying therapies are available such as oral and topical NSAIDs, opioids, SNRIs, etc., providing symptomatic treatment and functional improvement instead of suppressing OA progression. Long-term use of these therapies leads to various life-threatening complications. Interestingly, mother nature has numerous medicinal plants containing active phytochemicals that can act on various targets involved in the development and progression of OA. Phytochemicals have been used for millennia in traditional medicine and are promising alternatives to conventional drugs with a lower rate of adverse events and efficiency frequently comparable to synthetic molecules. Nevertheless, their mechanism of action in many cases is elusive and uncertain. Even though many in vitro and in vivo studies show promising results, clinical evidence is scarce. Studies suggest that the presence of carbonyl group in the 2nd position, chloro in the 6th and an electron- withdrawing group at the 7th position exhibit enhanced COX-2 inhibition activity in OA. On the other hand, the presence of a double bond at the C2-C3 position of C ring in flavonoids plays an important role in Nrf2 activation. Moreover, with the advancements in the understanding of OA progression, SARs (structure-activity relationships) of phytochemicals and integration with nanotechnology have provided great opportunities for developing phytopharmaceuticals. Therefore, in the present review, we have discussed various promising phytomolecules, SAR as well as their nano-based delivery systems for the treatment of OA to motivate the future investigation of phytochemical-based drug therapy.

Development of Novel Solid Nanostructured Lipid Carriers for Bioavailability Enhancement Using a Quality by Design Approach.

α, ß-Arteether (ART) antimalarial drug is used to treat chloroquine-resistant malaria and cerebral malaria. The drug's solubility in water is relatively low (17 µg/mL), and 40% of the drug degrades in the stomach, resulting in poor bioavailability. This article discusses the quality by design technique used for formulation development and optimization of nanostructured lipid carriers (NLCs). The ART-NLCs were made by solvent diffusion method. To develop solid NLCs, the NLCs were freeze-dried and encapsulated in enteric-coated capsule shells. The prepared NLCs showed particle size ranging between 156.8 ± 12 nm while zeta potential ranging between - 26.1 ± 0.22 mV. They also showed high encapsulation efficiency (> 85%) and an amorphous drug's lipid matrix state. Pharmacokinetic parameters of optimized formulation enhance oral bioavailability to 18.45%. These investigations demonstrated the superiority of NLCs for improvement of solubility as well as oral bioavailability of poorly water-soluble drugs.

Levofloxacin induced bullous fixed drug eruption: a rare case report.

A 42-year-old male patient visited the outpatient department for follow-up with a history of respiratory tract infection and diabetes mellitus. His main symptom was peeling of his epidermal layer of skin, and bullous fixed drug eruption on the lower and upper limbs and bank region of the body. Following assessment, the patient was prescribed levothyroxine, hydroxychloroquine, levofloxacin, and a combination of sulfamethoxazole-trimethoprim. On assessing causality of the adverse drug reaction (ADR), different ADR assessment scales such as the WHO-UMC Scale, Naranjo Scale, and Hartwig's Severity Assessment Scale were used, and the ADR was found by these scales to be 'likely', 'moderate', and 'probable', respectively. It was found that ADRs such as bullous fixed drug eruptions are not fatal but can cause patient anxiety and a reduced quality of life. This case report will help physicians and clinicians to become aware and vigilant about the ADR caused by levofloxacin, facilitating its early detection and management.

Impact of physical activity and cooking oil amongst diabetes with coexisting hypertension patients on economic cost and length of stay: A 1914 patient's observational study.

AIM OF THE STUDY: The study aimed to investigate the impact of the patients' physical activity status and the type of cooking oil consumed by patients in their daily routine on glycaemic profile, lipid profile, the hypertensive profile of the patients, the length of stay and overall cost of the treatment. METHODS: This is a prospective observational study. All the patients referred to the medicine department of the three different hospitals located in Moga, City Punjab, and those hospitalised due to diabetes mellitus (types I and II) with coexisting hypertension were asked to participate in the study. RESULTS: The patients' mean age was found to be M = 53.85, SD = 11.54 years. Out of 1914 patients, 914 were male (47.8%); it was observed that the majority of the patients 525 (27.43%) in North India using butter or ghee-clarified butter as edible oil, followed by mustard oil 517 (27.01%) patients. About 345 (18.03%) of the patients consume soybean oil, whereas 226 (11.81%) of the patients like sunflower oil. CONCLUSION: This study explored that cooking oil and physical activity are associated with length of stay in days and overall cost of the treatment, respectively. Our study results revealed that the type of oil compared with the treatment's overall cost was significant for olive oil, soybean oil and groundnut oil. The study revealed that moderate and low physical activity increases the length of stay compared to high physical activity. The consumption of olive oil as a regular food habit in daily routine decreases patients' length of stay with diabetes with coexisting hypertension when doing high physical activity but increases the overall cost of treatment.

How to spot COVID-19 patients: Speech & sound audio analysis for preliminary diagnosis of SARS-COV-2 corona patients.

BACKGROUND: The global cases of COVID-19 increasing day by day. On 25 November 2020, a total of 59 850 910 cases reported globally with a 1 411 216 global death. In India, total cases in the country now stand at 91 77 841 including 86 04 955 recoveries and 4 38 667 active cases as on 24 November 2020, as per the data issued by ICMR. A new generation of voice/audio analysis application can tell whether the person is suffering from COVID-19 or not. AIMS: To describe how to established a new generation of voice/audio analysis application to identify the suspected COVID-19 hidden cases in hotspot areas with the help of an audio sample of the general public. MATERIALS & METHODS: The different patents and data available as literature on the internet are evaluated to make a new generation of voice/audio analysis application with the help of an audio sample of the general public. RESULTS: The collection of the audio sample will be done from the already suffered COVID-19 patients in (.Wave files) personally or through phone calls. The audio samples such as the sound of the cough, the pattern of breathing, respiration rate and way of speech will be recorded. The parameters will be evaluated for loudness, articulation, tempo, rhythm, melody and timbre. The analysis and interpretation of the parameters can be made through machine learning and artificial intelligence to detect corona cases with an audio sample. DISCUSSION: The voice/audio application current project can be merged with a mobile App called 'AarogyaSetu' by the Government of India. The project can be implemented in the high-risk area of COVID-19 in the country. CONCLUSION: This new method of detecting cases will decrease the workload in the COVID-19 laboratory.

A Role for Extracellular Vesicles in SARS-CoV-2 Therapeutics and Prevention.

Extracellular vesicles (EVs) are the common designation for ectosomes, microparticles and microvesicles serving dominant roles in intercellular communication. Both viable and dying cells release EVs to the extracellular environment for transfer of cell, immune and infectious materials. Defined morphologically as lipid bi-layered structures EVs show molecular, biochemical, distribution, and entry mechanisms similar to viruses within cells and tissues. In recent years their functional capacities have been harnessed to deliver biomolecules and drugs and immunological agents to specific cells and organs of interest or disease. Interest in EVs as putative vaccines or drug delivery vehicles are substantial. The vesicles have properties of receptors nanoassembly on their surface. EVs can interact with specific immunocytes that include antigen presenting cells (dendritic cells and other mononuclear phagocytes) to elicit immune responses or affect tissue and cellular homeostasis or disease. Due to potential advantages like biocompatibility, biodegradation and efficient immune activation, EVs have gained attraction for the development of treatment or a vaccine system against the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection. In this review efforts to use EVs to contain SARS CoV-2 and affect the current viral pandemic are discussed. An emphasis is made on mesenchymal stem cell derived EVs' as a vaccine candidate delivery system.

Economic costs of hospitalisation and length of stay in diabetes with coexisting hypertension with correlation to laboratory investigations: Where does India stand? A 5-year ground report.

INTRODUCTION: The coexistence of diabetes mellitus (DM) and hypertension (HTN) worsens clinical outcomes and contributes to increased morbidity and mortality. OBJECTIVE: This study aims to analyse the length of stay and healthcare costs by calculating the direct and indirect costs of diabetes with coexisting hypertension in North India. METHODS: A prospective observational study was conducted at the medicine department of the three different hospitals. RESULTS: The patients' mean age was (M = 53.8, SD = 11.5) years. Out of 1914 patients, 53.65% were female. Our study revealed that the median cost of medical supplies and equipment was 21.2 $. The median cost of dialysis was 47.5 $; the median cost of hospitalisation was 142.6 $. The treatment's median direct cost was 188.5 $, followed by the overall median cost of 295.6 $. The maximum overall cost of treatment was observed at 603.9 $. It was observed that maximum LOS was 14 days for patients having BPS between 140 and 159 mmHg and BPD between 110 and 119 mmHg, and minimum LOS was found 3.5 days. CONCLUSION: The present study highlighted that diabetes coexisting hypertension poses a high-economic burden on patients. This study explored that highly significant result for BPS, BPD, FBS and HbA1 c, whereas the significant results were obtained when RBS is compared with LOS and treatment costs. Our study concluded that mean difference of 9.24 $ in patients having FBS was 261-290 mg/dL and >290 mg/dL. The LOS is increased by 6.57 days for patients with BPS between 140 and 159 mmHg compared with BPS between 180 and 209 and above mmHg, which lowers treatment costs by -21.31$.

Nanocarrier vaccines for SARS-CoV-2.

The SARS-CoV-2 global pandemic has seen rapid spread, disease morbidities and death associated with substantive social, economic and societal impacts. Treatments rely on re-purposed antivirals and immune modulatory agents focusing on attenuating the acute respiratory distress syndrome. No curative therapies exist. Vaccines remain the best hope for disease control and the principal global effort to end the pandemic. Herein, we summarize those developments with a focus on the role played by nanocarrier delivery.

Chloro and bromo-pyrazole curcumin Knoevenagel condensates augmented anticancer activity against human cervical cancer cells: design, synthesis, in silico docking and in vitro cytotoxicity analysis.

With an endeavor to develop novel curcumin analogs as potential anti-cancer agents, we designed and synthesized a series of Knoevenagel condensates by clubbing pyrazole carbaldehydes at the active methylene carbon atom of the curcumin backbone. Molecular docking studies were carried out to target the proposed derivatives on human kinase ß (IKKß), a potential anti-cancer target. The chloro derivative displayed five hydrogen bond interactions with a docking score of -11.874 kcal/mol higher than curcumin (docking score = -7.434 kcal/mol). This was supported by the fact that the propellant shaped derivatives fitted aptly into the binding pocket. Molecular simulations studies were also conducted on the lead molecule and the results figured out that the stable complexes were developed as the minimal deviations per residue of protein within the range of 0.11-0.92 Å. The screened compounds were synthesized, characterized and evaluated in vitro for cytotoxicity against cervical cancer cell line, HeLa using standard cell proliferation assay. Chloro derivative and bromo analog demonstrated IC50 (half maximal inhibitory concentration) value of 14.2 and 18.6 µg/ml, respectively, significantly lower than 42.4 µg/ml of curcumin and higher than 0.008 µg/ml of paclitaxel. Induction of apoptosis was evaluated in the terms of cleavage of caspase-3 enzyme and they also exhibited 69.6 and 65.4% of apoptosis significantly higher than 19.9% induced by curcumin. In conclusion, chloro and bromo derivatives must be evaluated under a set of stringent in vitro and in vivo parameters for translating in to a clinically viable product.Communicated by Ramaswamy H. Sarma.

4-Bromo-4'-chloro pyrazoline analog of curcumin augmented anticancer activity against human cervical cancer, HeLa cells: in silico-guided analysis, synthesis, and in vitro cytotoxicity.

Inspired by the synergistic effects of hetero-aromatic scaffolds on curcumin, a novel array of pyrazoline substituted curcumin analogs was designed. Multi-scale computational studies were carried out to target the proposed analogs on human kinase ß (IKK-ß), a potential anti-cancer target. In molecular docking analysis, all the eleven molecules were observed to bind the target site and 4-bromo-4'-chloro analog displayed three hydrogen bond interactions with a docking score of -11.534 kcal/mol higher than parent molecule, curcumin (docking score = -7.12 kcal/mol) as the propellant shaped of analogs aided in proper binding with Kinase Domain binding pocket. The molecular dynamics and simulations studies revealed that the stable complexes of lead molecule were developed as the minimal deviations per residue of protein found within the range of 0.11 to 0.92 Å. The proposed compounds were synthesized, characterized and biologically evaluated against human cervical cancer cell line, HeLa, using standard MTT cell assay. Bio-evaluation studies exhibited superior cytotoxic profile for many analogs as Chloro bromo analog with IC50 value (8.7 µg/mL) exhibited fivefolds improvement in the potency in comparison to curcumin (IC50 = 42.4 µg/mL) but was less potent than the standard drug, paclitaxel (IC50 = 0.008µg/mL). The apoptotic effect was evaluated in the terms of caspase-3 enzyme cleavage and exhibited 70.5% of apoptosis significantly (p < 0.05) higher than 19.9% induced by curcumin. In short, 4-bromo-4'-chloro analog was the potent cytotoxic agent in this structural class and must be evaluated further under a set of stringent parameters for transforming in to a clinically viable therapeutic molecule.Communicated by Ramaswamy H. Sarma.

Imiquimod-oleic acid prodrug-loaded cream reduced drug crystallinity and induced indistinguishable cytotoxicity and apoptosis in mice melanoma tumour.

In the present investigation, imiquimod (IMQ) was coupled to oleic acid (OLA; IMQ-OLA) to synthesise prodrug to reduce crystallinity that later amalgamated with oil-in-water (o/w) emulsion cream (IMQ-OLA cream) for the treatment of melanoma tumour. The synthesis of IMQ-OLA prodrug was verified by FT-IR, 1HNMR and mass spectroscopy. The crystalline lattice of IMQ was transformed to somewhat amorphous structure in IMQ-OLA prodrug. IMQ-OLA cream retained 35.6% of IMQ within skin, significantly (p < 0.05) higher than 22.3% and 10.6% retained by marketed IMQ cream and IMQ solution, respectively. IMQ-OLA cream suppressed the melanoma tumour to 70.3 mm3 in C57BL6J mice as compared to 72.6 mm3 tumour, reduced by marketed IMQ cream with no significant difference (p > 0.05) at day 32 over 17-day period of treatment. IMQ-OLA cream followed the multiple mechanisms of cell death. IMQ-OLA cream warrants further in depth investigations for translating in to a clinically viable topical dermal product.

Recent Advances in Solid Dispersion Technology for Efficient Delivery of Poorly Water-Soluble Drugs.

Drug discovery is generally considered as a costly affair and it takes approximately 15 years to reach a new chemical entity into the market. Among the recent potent drug molecules with most effective pharmacological properties, very few reached for Phase I clinical trial in humans. Unfortunately, the historical average reveals an almost 90% overall attrition rate in clinical trials. The solubility and permeability of a drug are the critical factors influencing the success of a drug. Oral drug delivery systems still continue to exist as the most favored, simplest and easiest administration route. A huge number of potential clinical candidates won't make it to the market or accomplish their maximum capacity except if their solubility and oral bioavailability are enhanced by formulation. The solubility of drugs will continue to exist as important aspects of formulation development. With the emergence of synthetic methods for new molecule synthesis in chemistry and better screening methods, the number of poorly water soluble compounds has dramatically expanded in the last few years. Solid dispersion is one of the most important techniques as it can be prepared by several methods. It is mostly prepared with a drug having poor water solubility and it explores hydrophilic polymers either individually or in combination for the enhancement of solubility. In comparison to the conventional formulations such as tablets or capsules, there are different methods with which solid dispersions can be prepared and also have many benefits over conventional drug delivery approaches. Solid dispersion systems are potential for increasing the solubility, oral absorption and bioavailability of drugs and the significance of the solid dispersion technology is constantly increasing. The main focus of this review is to present recent advancements in the area of solid dispersion. This review also includes an account of recent patents on solid dispersion and clinical status of solid dispersion based formulations.

Optimization of sulfation of okra fruit gum for improved rheological and pharmacological properties.

In the present investigation, sulfated derivatives of Okra fruit gum (OFG) with the degree of substitution (DS) ranging from 0.39 to 1.13 were synthesized using chlorosulfonic acid/pyridine (CSA/Py) reagents under the umbrella of Box-Behnken Design (BBD) of Response Surface Methodology (RSM) to optimize the reaction conditions. The extracted gum was characterized for particle size, zeta-potential, surface morphology, architectural arrangement, mechanical and rheological chattels, pharmacological properties etc. The optimal reaction conditions of sOFG (sulfated okra fruit gum) were included ratio of CSA/Py, 0.28; reaction time, 3.05 h and reaction temperature, 58.74 °C. A high DS of 1.004 was procured at optimized conditions that was analogous to the predicted value. The sOFG was investigated to be advanced over the immensely used polysaccharide sodium alginate in mechanical and rheological attributes. Also, pharmacological properties including anticoagulant and antimicrobial property of sOFG were superior as compared to OFG. In conclusion, sulfation of OFG under the shed of BBD offered a superior DS that could be further explored for wide usage as pharmaceutical excipient for designing health care products.

Recent Advances in Formulation Strategies for Efficient Delivery of Vitamin D.

Deficiency of vitamin D is a global concern affecting a huge number of human populations. This deficiency has a serious impact on human health not only affecting bone mineral density but also becoming the reason for cardiovascular disorders, infectious diseases, autoimmune diseases and cancers. Exposure to sunlight is the major source of vitamin D, but due to the present day-to-day lifestyle of working in a shade arouses the need for exogenous sources of vitamin D. Ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3) are the two major forms of vitamin D, which are hydrophobic in nature and highly susceptible to environmental conditions, like temperature and light. Therefore, novel drug delivery systems could be explored for efficient delivery of vitamin D. In this review, a brief account of vitamin D is provided followed by a detailed description of recent advances in various delivery systems, including solid lipid nanoparticles, nanoemulsion, self-emulsifying drug delivery systems, polymeric nanoparticles and solid dispersion, for the efficient delivery of vitamin D.

Nanoparticles as carriers for drug delivery in cancer.

Cancer nanotherapeutics are swiftly progressing and are being applied to solve several limitations of conventional drug delivery systems such as non-specific biodistribution and targeting, lack of water solubility and poor oral bioavailability. Advances in protein engineering and materials science have contributed to novel nanoscale targeting approaches that may bring new hope to cancer patients. Several therapeutic nanocarriers have been approved for clinical use. Nanoparticles have been designed for optimal size and surface characteristics to improve their biodistribution and to increase their circulation time in the bloodstream. By selectively using the unique pathophysiology of tumours, such as their enhanced permeability and retention effect nanotherapeutics are able to carry loaded active drug to cancer cells. In addition to this passive targeting mechanism, active targeting strategies using ligands or antibodies directed against selected tumour targets magnify the specificity of these therapeutic nanoparticles. Drug resistance, another obstacle can also be overcome or reduced by using nanoparticles. Multifunctional and multiplex nanoparticles are now being actively investigated and are on the horizon as the next generation of nanoparticles, facilitating personalized and tailored cancer treatment.

Armamentarium of nanoscaled lipid drug delivery systems customized for oral administration: In silico docking patronage, absorption phenomenon, preclinical status, clinical status and future prospects.

Poor drug solubility and bioavailability remain a significant and frequently encountered concern for pharmaceutical scientists. Nanoscaled lipid drug delivery systems (NSLDDS) have exhibited great potentials in oral delivery of poorly water-soluble drugs, primarily for lipophilic drugs, with several successful clinical products. In the past few years, we have find out that optimized composition of drug in lipid, surfactant, or mixture of lipid and surfactant omits the solubility, permeability and bioavailability issues, which are potential limitations for oral absorption of poorly water-soluble drugs. Lipids not only vary in structures and physiochemical properties, but also in their digestibility and absorption pathway; therefore selection of lipid excipients and dosage form has a pronounced effect on biopharmaceutical aspects of drug absorption and distribution both in vitro and in vivo. Therefore, in current critical review, a comprehensive overview of the different lipid based nanostructured drug delivery systems intended for oral administration has been presented. In addition, implication of in silico docking in designing of NSLDDS as well as mechanism of absorption of different lipid based nanoformulations through intestinal absorption window has also been offered. Moreover, attention has also been paid to NSLDDS that are currently undergoing preclinical or clinical analysis.