Design and development of bioinspired calcium phosphate nanoparticles of MTX: pharmacodynamic and pharmacokinetic evaluation.

The aim of this investigation is the management of rheumatoid arthritis (RA) by developing methotrexate-loaded calcium phosphate nanoparticles (MTX-CAP-NP) and to evaluate pharmacokinetic and pharmacodynamic behavior in adjuvant induced arthritis model. The nanoparticles were synthesized by wet precipitation method and optimized by Box-Behnken experimental design. MTX-CAP-NPs were characterized by TEM, FTIR, DSC and XRD studies. The particle size, zeta potential and entrapment efficiency of the optimized nanoparticles were found to be 204.90 ± 64 nm, -11.58 ± 4.80 mV, and 88.33 ± 3.74%, respectively. TEM, FTIR, DSC and XRD studies revealed that the developed nanoparticles were nearly spherical in shape and the crystalline structure of CAP-NP was not changed after MTX loading. The pharmacokinetic studies revealed that MTX-CAP-NP enhanced bioavailability of MTX by 2.6-fold when compared to marketed formulation (FOLITRAX-10). Under pharmacodynamic evaluation, arthritic assessment, radiography and histopathology studies revealed that CAP has ability to regenerate cartilage and bone therefore, together with MTX, MTX-CAP-NPs have shown significant reduction in disease progression. The overall work demonstrated that the developed nanodelivery system was well tolerated and more effective than the marketed formulation.

Potential of Lipid Nanoparticles (SLNs and NLCs) in Enhancing Oral Bioavailability of Drugs with Poor Intestinal Permeability.

Lipid-based drug delivery systems has become a popular choice for oral delivery of lipophilic drugs with dissolution rate limited oral absorption. Lipids are known to enhance oral bioavailability of poorly water-soluble drugs in multiple ways like facilitating dissolution as micellar solution, enhancing the lymphatic uptake and acting as inhibitors of efflux transporters. Lipid nanoparticles are matrix type lipid-based carrier systems which can effectively encapsulate both lipophilic and hydrophilic drugs. Lipid nanoparticles namely solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) are versatile drug delivery system and can be used for multiple routes of delivery like parenteral, topical, ocular, transdermal, and oral. Lipid nanoparticles are particularly attractive vehicles for peroral delivery of drugs with oral bioavailability problems as they are composed of lipid excipients which are cheap, easily available, and non-toxic; manufacturing technique is simple and readily scalable for large-scale production; the formulations provide controlled release of active components and have no stability issue. A large number of drugs have been incorporated into lipid nanoparticles with the objective of overcoming their poor oral bioavailability. This review tries to assess the potential of lipid nanoparticles for enhancing the oral bioavailability of drugs with permeability limited oral absorption such as drugs belonging to class IV of Biopharmaceutic Classification System (BCS) and protein and peptide drugs and also discusses the mechanism behind the bioavailability enhancement and safety issues related to such delivery systems.

Co-Delivery of Teriflunomide and Methotrexate from Hydroxyapatite Nanoparticles for the Treatment of Rheumatoid Arthritis: In Vitro Characterization, Pharmacodynamic and Biochemical Investigations.

PURPOSE: The present investigation was aimed at developing Teriflunomide (TEF) and Methotrexate (MTX) loaded hydroxyapatite nanoparticles and increasing tolerability towards combination therapy against rheumatoid arthritis by reducing hepatotoxicity. METHODS: Drug-loaded HAp-NPs were synthesized by wet-chemical precipitation method and optimized by Box-Behnken experimental design. The developed NPs were subjected to in vitro and in vivo characterization. In-vivo pharmacodynamics and biochemical studies were performed on adjuvant- induced arthritis model treated with different formulations; MTX-TEF-SOL, TEF-HAp-NP, MTX-HAp-NP, TEF-MTX-HAp-NP, FOLITRAX-10 and AUBAGIO. RESULTS: The size of the optimized formulations, TEF-HAp-NP and MTX-HAp-NP, was found to be 224.3 ± 83.80 nm and 268.3 ± 73.86 nm with drug loading 53.11 ± 0.84% and 67.04 ± 1.12% respectively. In vitro release of TEF from TEF-HAp-NP (70.41 ± 1.22%) and MTX from MTX-HAp-NP (82.43 ± 1.31%) up to 24 h revealed sustained release pattern. Results of the arthritic assessment study showed a significant (P < 0.05) reduction in ankle diameter (61.30 ± 7.42) and arthritis score (2.35 ± 0.24) with a marked restoration of ankle joint micro-architecture in TEF-MTX-HAp-NP treated group. During Hepatotoxicity studies, liver histopathology revealed that the formulation MTX-TEF-HAp-NP was least hepatotoxic with less hepatocyte swelling and fibrous connective tissue proliferation while Folitrax-10 was found to be most hepatotoxic. Biochemical studies revealed that Folitrax-10 significantly (P < 0.05) increased the GOT (313.64 ± 16) and GPT level (334.46 ± 13) while insignificant (P > 0.05) change in GOT (263.68 ± 17) and GPT (229.38 ± 10) level was recorded with TEF-MTX-HAp-NP. CONCLUSIONS: We report that the subcutaneous delivery of TEF-MTX-HAp-NP was most effective as it successfully reduced the dosage by half for maximizing therapeutic efficacy and minimizing side effects. Graphical Abstract ᅟ.

Development and validation of stability indicating reversed-phase liquid chromatographic method for simultaneous quantification of methotrexate and teriflunomide in nanoparticles and marketed formulation.

Methotrexate (MTX) and teriflunomide (TEF) are the two most effective disease-modifying antirheumatic drugs used as combination therapy for rheumatoid arthritis and no robust high-performance liquid chromatography (HPLC) method is available for their simultaneous estimation to date. Therefore, we have developed and validated an isocratic reversed-phase HPLC method for simultaneous analysis of MTX and TEF spiked in the form of active pharmaceutical ingredients, tablets and nanoformulations. The best separation was achieved on a BDS, C18 , 4.6 × 250 mm, 5 µm analytical column (Thermo Hypersil) with methanol-ethylammonium formate-potassium dihydrogen phosphate buffer (55 mm, pH 3.5; 65:5:30, v/v) as mobile phase at a flow rate of 0.8 mL/min. All the samples were subjected to force degradation studies. Responses of MTX and TEF were found to be a linear function of concentration over the range 1-50 µg/mL (r2 = 0.9976 and 0.9982). The limits of detection and limit of quantification were 7.74 and 25.82 ng/mL and 10.74 and 35.80 ng/mL, respectively. Degradation products produced under the stress studies did not interfere with the detection of MTX and TEF and therefore the developed method can be regarded as stability indicating.

Appraisal of Transdermal Water-in-Oil Nanoemulgel of Selegiline HCl for the Effective Management of Parkinson's Disease: Pharmacodynamic, Pharmacokinetic, and Biochemical Investigations.

In the present study, the potential of transdermal nanoemulsion gel of selegiline hydrochloride for the treatment of Parkinson's disease was investigated. Water-in-oil nanoemulsions were developed by comparing low- and high-energy methods and were subjected to thermodynamic stability tests, in vitro permeation, and characterization studies. In vitro studies indicated that components of nanoemulsion acted as permeation enhancers with highest flux of 3.531 ± 1.94 µg/cm2/h from nanoemulsion SB6 containing 0.5 mg selegiline hydrochloride, 3% distilled water, 21% S mix (Span 85, Tween 80, PEG 400), and 76% isopropyl myristate by weight. SB6 with the least droplet size of 183.4 ± 0.35 nm, polydispersity index of 0.42 ± 0.06 with pH of 5.9 ± 0.32 and viscosity of 22.42 ± 0.14 cps was converted to nanoemulsion gel NEGS4 (viscosity = 22,200 ± 400 cps) by addition of Viscup160® for ease of application and evaluated for permeation, safety, and pharmacokinetic profile in Wistar rats. It provided enhancement ratio 3.69 times greater than conventional gel. NEGS4 showed 6.56 and 5.53 times increase in bioavailability in comparison to tablet and conventional gel, respectively, along with sustained effect. Therefore, the developed water-in-oil nanoemulsion gel promises to be an effective vehicle for transdermal delivery of selegiline hydrochloride.

Design and Development of Bioceramic Based Functionalized PLGA Nanoparticles of Risedronate for Bone Targeting: In-vitro Characterization and Pharmacodynamic Evaluation.

PURPOSE: Bioceramic(Hydroxyapatite) based Poly(D,L-lactide-co-glycolide) (PLGA) and polyethylene glycol (PEG) nanoparticles of Risedronate was prepared by dialysis method for bone-targeting. METHODS: Risedronate, a targeting moiety that has a strong affinity for bone, was conjugated to PLGA via carbodiimide chemistry. Mono-methoxy PEG(mPEG)-PLGA block polymers were synthesized and used to impart surface hydrophilicity to nanoparticles to avoid its uptake by reticuloendothelial system (RES). The structure of prepared di block copolymers were characterized by FT-IR and NMR spectrometry. Risedronate was adsorbed on the surface of hydroxyapatite (RIS-HA) and it was conjugated with different ratios of mPEG-PLGA. The formation of surface-modified PLGA nanoparticle prepared with various ratios of risedronate as well as hydroxyapatite and mPEG was confirmed by (1)H NMR and FT-IR spectrometry. RESULTS: Size and % entrapment of the prepared nanoparticle was found to be 79.3 ± 2.3 nm and 93 ± 3.1%. Transmission electron microscopy (TEM) revealed that mPEG-PLGA-RIS-HA nanoparticles possess smooth and uniform surface. Pharmacodynamic study was performed on Dexamethasone (DEX) induced osteoporotic model. The effect of various formulations (mPEG-PLGA-RIS, mPEG-PLGA-RIS-HA and RISOFOS tablet) on bone was studied by Volume bone density (VBD) and by histopathological evaluation. Interestingly mPEG-PLGA-RIS-HA, showed a significant enhancement in bone micro-architecture when compared with other formulations. CONCLUSIONS: The results strongly implicated that mPEG-PLGA-RIS-HA has a therapeutic benefits over risedronate sodium monotherapy for the treatment of osteoporosis in a rat model.

Multifaceted role of phytoconstituents based nano drug delivery systems in combating TNBC: A paradigm shift from chemical to natural.

Triple negative breast cancer is considered to be a malignancy of grave concern with limited routes of treatment due to the absence of specific breast cancer markers and ambiguity of other potential drug targets. Poor prognosis and inadequate survival rates have prompted further research into the understanding of the molecular pathophysiology and targeting of the disease. To overcome the recurrence and resistance mechanisms of the TNBC cells, various approaches have been devised, and are being continuously evaluated to enhance their efficacy and safety. Chemo-Adjuvant therapy is one such treatment modality being employed to improve the efficiency of standard chemotherapy. Combining chemo-adjuvant therapy with other upcoming approaches of cancer therapeutics such as phytoconstituents and nanotechnology has yielded promising results in the direction of improving the prognosis of TNBC. Numerous nanoformulations have been proven to substantially enhance the specificity and cellular uptake of drugs by cancer cells, thus reducing the possibility of unintended systemic side effects within cancer patients. While phytoconstituents offer a wide variety of beneficial active constituents useful in cancer therapeutics, most favorable outcomes have been observed within the scope of polyphenols, isoquinoline alkaloids and isothiocyanates. With an enhanced understanding of the molecular mechanisms of TNBC and the advent of newer targeting technologies and novel phytochemicals of medicinal importance, a new era of cancer theranostic treatments can be explored. This review hopes to instantiate the current body of research regarding the role of certain phytoconstituents and their potential nanoformulations in targeting specific TNBC pathways for treatment and diagnostic purposes.

Surface Functionalized Lipid Nanoparticles in Promoting Therapeutic Outcomes: An Insight View of the Dynamic Drug Delivery System.

Compared to the conventional approach, nanoparticles (NPs) facilitate a non-hazardous, non-toxic, non-interactive, and biocompatible system, rendering them incredibly promising for improving drug delivery to target cells. When that comes to accomplishing specific therapeutic agents like drugs, peptides, nucleotides, etc., lipidic nanoparticulate systems have emerged as even more robust. They have asserted impressive ability in bypassing physiological and cellular barriers, evading lysosomal capture and the proton sponge effect, optimizing bioavailability, and compliance, lowering doses, and boosting therapeutic efficacy. However, the lack of selectivity at the cellular level hinders its ability to accomplish its potential to the fullest. The inclusion of surface functionalization to the lipidic NPs might certainly assist them in adapting to the basic biological demands of a specific pathological condition. Several ligands, including peptides, enzymes, polymers, saccharides, antibodies, etc., can be functionalized onto the surface of lipidic NPs to achieve cellular selectivity and avoid bioactivity challenges. This review provides a comprehensive outline for functionalizing lipid-based NPs systems in prominence over target selectivity. Emphasis has been put upon the strategies for reinforcing the therapeutic performance of lipidic nano carriers' using a variety of ligands alongside instances of relevant commercial formulations.

A logical approach to optimize the nanostructured lipid carrier system of irinotecan: efficient hybrid design methodology.

Development of an effective formulation involves careful optimization of a number of excipient and process variables. Sometimes the number of variables is so large that even the most efficient optimization designs require a very large number of trials which put stress on costs as well as time. A creative combination of a number of design methods leads to a smaller number of trials. This study was aimed at the development of nanostructured lipid carriers (NLCs) by using a combination of different optimization methods. A total of 11 variables were first screened using the Plackett-Burman design for their effects on formulation characteristics like size and entrapment efficiency. Four out of 11 variables were found to have insignificant effects on the formulation parameters and hence were screened out. Out of the remaining seven variables, four (concentration of tween-80, lecithin, sodium taurocholate, and total lipid) were found to have significant effects on the size of the particles while the other three (phase ratio, drug to lipid ratio, and sonication time) had a higher influence on the entrapment efficiency. The first four variables were optimized for their effect on size using the Taguchi L9 orthogonal array. The optimized values of the surfactants and lipids were kept constant for the next stage, where the sonication time, phase ratio, and drug:lipid ratio were varied using the Box-Behnken design response surface method to optimize the entrapment efficiency. Finally, by performing only 38 trials, we have optimized 11 variables for the development of NLCs with a size of 143.52 ± 1.2 nm, zeta potential of -32.6 ± 0.54 mV, and 98.22 ± 2.06% entrapment efficiency.

A validated stability-indicating LC method for estimation of etoposide in bulk and optimized self-nano emulsifying formulation: Kinetics and stability effects.

The present investigation was aimed to establish a validated stability-indicating liquid chromatographic method for the estimation of etoposide (ETP) in bulk drug and self-nano emulsifying formulation. ETP was successfully separated from the degradation products formed under stress conditions on LiChrospher 100 C18 reverse-phase column (a 250 mm × 4.6 mm i.d., 5-µm particle size) using 55:45 (v/v) acetonitrile-phosphate buffer saline (pH 4.5) as the mobile phase, at a flow rate of 1.0 mL min(-1) and detection at 283 nm. The response was a linear function of analyte concentration (R(2) > 0.9997) over the concentration range of 0.05-50 µg mL(-1). The method was validated for precision, accuracy, robustness, sensitivity and specificity. The % recovery of ETP at three different levels (50%, 100% and 150%) ranged between 93.84% and 100.06% in optimized self-nano emulsifying formulation, Etosid® soft-gelatin capsule and Fytosid® injection. First-order degradation kinetics of ETP were observed under acidic and alkaline conditions. The method was also applied for the stability assessment of self-nano emulsifying formulation under accelerated conditions, the formulation was found to be stable at all storage conditions with the shelf-life of 2.37 years at 25 °C. The method holds promise for routine quality control of ETP in bulk, pharmaceutical formulations as well as in stability-indicating studies.

An approach for lacidipine loaded gastroretentive formulation prepared by different methods for gastroparesis in diabetic patients.

The present work deals with various attempts to prepare a gastroretentive formulation of lacidipine for treating gastroparesis. High density sucrose beads were modified by coating with certain polymers, but unfortunately sustained release could not be achieved. Granules were prepared by wet granulation technology using different combinations of polymers and a release of the drug was observed. The method failed to release the drug as per desired specifications. Polymeric coating followed by wet granulation was thought to be a better process to sustain the dissolution rate. The release rate can be modified by the incorporation of different polymeric coatings, but the mucoadhesive potential of granules was only 4.23% which might be due to its large size and the presence of other ingredients. Further, the lacidipine loaded microparticles were prepared by different methods such as compression, ionic gelation with TPP, ionic gelation with TPP and glutaraldehyde, spray drying and coacervation techniques. The formulations were evaluated for average particle size, surface morphology, entrapment efficiency, % yield and mucoadhesive potential. The microparticles prepared by compression method using HPMC K4M and SCMC as mucoadhesive polymers and BaSO4 as high density diluent showed poor bioadhesion (8.3%) and poor release characteristics (100% in 120 min). Ionic gelation with tripolyphosphate yielded microspheres with poor mechanical strength. In order to improve its mechanical strength, TPP ionic gelation was combined with step-wise cross-linking with glutaraldehyde. The additional solidification step to improve mechanical strength left this procedure tedious, time consuming and cytotoxic. Spray drying method gave a very low yield with 46.67% bioadhesion. The method using CaCl2 for ionotropic gelation showed the best results with regard to physical characteristics (well formed discrete, spherical surface microcapsule), particle size (88.57 ± 0.51), in vitro bioadhesion (67.33%), yield (>85%) and loading (>70%).

Digital Intervention For The Management Of Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive, multifactorial, chronic, neurodegenerative disease with high prevalence and limited therapeutic options, making it a global health crisis. Being the most common cause of dementia, AD erodes the cognitive, functional, and social abilities of the individual and causes escalating medical and psychosocial needs. As yet, this disorder has no cure and current treatment options are palliative in nature. There is an urgent need for novel therapy to address this pressing challenge. Digital therapeutics (Dtx) is one such novel therapy that is gaining popularity globally. Dtx provides evidence based therapeutic interventions driven by internet and software, employing tools such as mobile devices, computers, videogames, apps, sensors, virtual reality aiding in the prevention, management, and treatment of ailments like neurological abnormalities and chronic diseases. Dtx acts as a supportive tool for the optimization of patient care, individualized treatment and improved health outcomes. Dtx uses visual, sound and other non-invasive approaches for instance-consistent therapy, reminiscence therapy, computerised cognitive training, semantic and phonological assistance devices, wearables and computer-assisted rehabilitation environment to find applications in Alzheimer's disease for improving memory, cognition, functional abilities and managing motor symptom. A few of the Dtx-based tools employed in AD include "Memory Matters", "AlzSense", "Alzheimer Assistant", "smart robotic dog", "Immersive virtual reality (iVR)" and the most current gamma stimulation. The purpose of this review is to summarize the current trends in digital health in AD and explore the benefits, challenges, and impediments of using Dtx as an adjunctive therapy for the management of AD.

Uncovering caregiver concerns: 5 key issues that still remain unresolved in administration of oral medicines for children in India.

INTRODUCTION: Administration devices play a very crucial role in achieving a drug's therapeutic effect. Children are often dosed with oral liquids, but dosing devices don't have the accuracy needed, putting them at risk of inaccurate and suboptimal dosing. The availability and use of administration devices may vary throughout the world. Multiple surveys in UK, Europe and Japan have shown diverging practices by parents/caregivers. The aim of the present investigation was to conduct a larger Pan-India study through a series of workshops to understand the use and challenges of traditional devices and assess the need of innovative administration devices for liquid orals in India. METHODS: The methodology used for the workshop was contextual inquiry and survey questionnaire were used to record the responses. Parents for the workshop were recruited by advertising the survey on various social media platforms. Informed consent was taken from the parents or caregivers for their participation in the survey. Workshops were conducted pan India and both middle class and urban worker families in the occupational category were included in the study. During the workshop, the parents were briefed about the background and purpose of the study. Certain global innovative devices such as oral syringes, syringes with pacifiers were shown to the parents. Their views and opinions were taken through survey questionnaire and via interactive sessions. The questions were themed for the interactive session on 1) challenges faced, 2) willingness to use innovative devices and 3) the factors influencing their decision on the use of innovative devices. RESULTS: Across the four regions (4 metro cities) involved in the study, 271 caregivers agreed to participate in the workshops. 17.7 % administered solid dosage forms, 81.2 % administered liquid dosage form and the remaining 1.1 % opted for others. TRADITIONAL DEVICES: Caregivers reported the use of measuring cups (41.4 %) followed by household spoons (25.8 %), droppers (15.3 %), measuring spoons (2.6 %), and other dosing devices (5.5 %) for measuring oral liquids. 8.0 % did not use any of the dosing devices as they were administrating tablets and/or capsules. The ease-of-use score was the highest for the dropper (2.67 ± 0.68) and the lowest for the measuring spoon (2.00 ± 1.00). The reported challenges were categorised into five categories which also influences the preference of using administration devices. This includes device design, user experience and usability, sociocultural factors, such as beliefs, knowledge and education, regulatory, and market/distribution. INNOVATIVE DEVICES: The majority of the caregivers (86.7 %) were not aware of any of the innovative devices shown to them. 58.7 % were willing to use it if was recommended by the doctor, 1.5 % of caregivers would use it on pharmacists' recommendation and 37.6 % parents would use it if came along with the medicine. The criteria considered by the parents for use of the innovative devices in the descending order were Doctor's recommendation > Quality > Cost > Packed in medicine > Ease of use > Availability/accessibility. There were no differences observed among the low and high socioeconomic status of caregviers regarding the use of traditional devices, challenges faced and awareness about innovative devices. Overall, the study revealed heterogeneity in the SES for the use of administration devices in the four zones. The association of SES and opinion on the use of administration devices was demonstrated with no statistically significant interaction between caregiver SES and the use of administration devices. CONCLUSION: The workshop revealed the prevalence of traditional dosing devices like measuring cups, household spoons among the caregivers. It highlighted key issues with the use of appropriate administration devices for correct and accurate dosing in children that remain unresolved and prevalent in India. This study reflects on the needs of the target community; thus hope will help facilitate the development of locally sustainable solutions to improve the administration of medicines in children in India.

Stepping into small shoes: Gaining user perspective on appropriate administration devices for paediatric medication in India.

A cross sectional pan-India study about use of administration devices for paediatric oral and inhalation medicines was conducted with a diverse pool of participants of various age groups. Via 634 respondents from more than 15 states in India, this study has identified the administration devices commonly used by parents/caregivers for children 0 to 18 years and by children over 10 years. It has provided insights on device ease of use, challenges faced and recommendations to facilitate the correct use of administration devices for paediatric oral and inhalation medicines. Ethics approval (DPSRU-BREC/2020/A/008)) was obtained from the Biomedical Research Ethics Committee of Delhi Pharmaceutical Sciences and Research University. The survey was completed by parents only (n = 514) and jointly by both parents and children (n = 120). The mean age of the child was 7.2 ± 4.96 years. 72% of the respondents reported that an oral medicine had been taken recently, 6.3% reported that an inhaled medicine had been taken and the remaining 21.9% reported that both an oral and inhaled medicine had been taken. The use of measuring cup was most prevalent followed by household spoons. The mean of the score for ease of use was found to be highest 4.6 ± 0.50 for oral syringe and lowest (3.8 ± 0.76) for measuring cups. The majority of them found the oral device easy to use. Difficulties were reported mostly for measuring cups and household spoons and were related to a lack of user instructions and measuring difficulties. The respondents who found the device easy to use had mostly received clear instructions from healthcare professionals. Compared to oral devices, there were very limited responses for inhalation devices (n = 175/634). Nebulisers with facemasks were most frequently used followed by manually actuated Metered dose inhalers with and without spacer. The mean of the ease-of-use score for dry powder inhalers was found to be highest (4.2 ± 0.37) followed by mist inhalers (4.0 ± 0) and manually actuated pressurised metered dose inhalers (4.0 ± 0.71). The nebulisers with facemask were reported to be difficult to use by most of the respondents despite receiving clear instructions from healthcare professionals. The study findings add evidence to the understudied area of user experiences and perspectives on administration devices for oral and inhalation medicines in India. It highlights a need for initiatives to improve the usability, availability, and affordability of administration devices for children in India. Awareness on the importance of proper use of devices needs to be raised and sustained about the existence of affordable administration devices.

Recent advancement on albumin nanoparticles in treating lung carcinoma.

With the advancement of nanotechnology, many different forms of nanoparticles (NPs) are created, which specifically enhance anticancer drug delivery to tumour cells. Albumin bio-macromolecule is a flexible protein carrier for the delivery of drugs that is biodegradable, biocompatible, and non-toxic. As a result, it presents itself as an ideal material for developing nanoparticles for anticancer drug delivery. Toxicological investigations demonstrated that this novel drug delivery technique is safe for use in the human population. Furthermore, drug compatibility with the albumin nanoparticle is remarkable. The robust structure of the nanoparticle, high drug encapsulation, and customisable drug release make it a promising carrier option for the treatment of lung cancer. In this review, we summarise human serum albumin and bovine serum albumin in the targeted delivery of anticancer drugs to lung cancer cells.

CD44 mediated colon cancer targeting mutlifaceted lignin nanoparticles: Synthesis, in vitro characterization and in vivo efficacy studies.

Hyaluronic acid (HA) coated irinotecan loaded lignin nanoparticles (HDLNPs) were synthesized using ionic interaction method. Optimized nanoparticles were characterized for their active chemotherapeutic targeting potential to CD44 receptors overly-expressed on cancer cells. Blood component interaction studies supported hemocompatible nature of HDLNPs and also demonstrated their sustained plasma residence property. Cell anti-proliferation and mitochondrial depolarization studies on HT-29 cells suggest significantly (p < 0.01) improved chemotherapeutic efficacy of HDLNPs. In vitro cell based studies showed that nanoparticles have retained antioxidant activity of lignin that can prevent cancer relapse. In vivo biodistribution studies in tumor-bearing Balb/c mice confirmed improved drug localization in tumor site for longer duration. Tumor regression and histopathological studies indicated the efficacy ofligand-assisted targeting chemotherapy over the conventional therapy. Hematological and biochemical estimation suggested that irinotecan-associated myelosuppression, liver steatosis and rare kidney failure can be avoided by its encapsulation in HA-coated lignin nanoparticles. HDLNPs were found to be stable over a period of 12 months.

Recent Advancements in Lignin Valorization and Biomedical Applications: A Patent Review.

BACKGROUND: Synthetic polymers present disadvantages such as high cost, limited availability, safety concerns, environmental hazards and accumulation in body. Lignin, an aromatic biopolymer, is highly abundant and offers various advantages including cost-effectiveness, biocompatibility and biodegradability. It also possesses various pharmacological activities including antioxidant, antibacterial, anticancer and UV protection, thus lignin has become a popular biopolymer in recent years and is no more considered as bio-waste rather extensive research is been carried out on developing it as drug carrier. Lignin also has non-biomedical applications including dispersing agents, surfactants, detergent/ cleaning agents, energy storage, etc. Methods: This review compiles patents granted on production of technical lignin, different lignin therapeutic carriers and its biomedical and non-biomedical applications. The literature is collected from recent years including both articles as well as patents and is carefully analyzed and compiled in an easy to comprehend pattern for guiding future research. RESULTS: The reviewed patents and articles highlighted the advancement made in lignin isolation and valorization. Numerous lignin nanoformulations as drug delivery agents or as standalone entities with various pharmacological actions like antibacterial, antioxidant or UV protectant have been reported. As well as industrial applications of lignin as adhesives, insulators or supercapacitors have also made lignin a biopolymer of choice. CONCLUSION: Lignin being a bio-inspired polymer has huge potential in commercial applications. New methods of lignin isolation from lignocellulosic biomass including physical pretreatments, solvent fraction, and chemical and biological pretreatment have been widely patented. Several micro/nano lignin formulations with improved and controllable reactivity like nanocontainers, nanocapsules, nanoparticles have also been reported recently. Also, various pharmacological properties of lignin have also been explored, thus valorization of lignin is a hot topic of hour.

Formulation development and in vitro-in vivo assessment of protransfersomal gel of anti-resorptive drug in osteoporosis treatment.

Osteoporosis is a major cause of morbidity, mortality, and economic burden worldwide. Despite being an effective in combating the bone-deteriorating disorders, bisphosphonates have several shortcomings including poor and variable bioavailability, low permeability, high toxicity, etc. In this study, we developed and optimized protransfersome formulation for the drug risedronate sodium (RIS-Na) with the goal of enhancing its bioavailability and hence patient compliance. Phase separation coacervation technique was utilized for development of optimized formulation. Optimization was achieved by using three-factor, three-level Box-Behnken design combined with Response Surface Methodology (RSM). This enabled us to decipher the effect of 3 independent variables (Phospholipid, Tween-80 and Sodium Deoxycholate) on three dependent parameters (entrapment efficiency, vesicle size and transdermal flux). Optimized formulation was further evaluated for pharmacokinetic and pharmacodynamic parameters. Smooth, spherical protransfersomes with a size of 260 ± 18 nm, having entrapment efficiency and flux of 80.4 ± 4.90% and 8.41 ± 0.148 µg/cm2/h, respectively were prepared. Ex vivo studies revealed a shorter lag time of 1.21 ± 0.18 h and higher flux associated with transdermal formulation. CLSM analysis further revealed better drug penetration (220 µm) through the skin in case of protransfersomes as compared to drug solution (72 µm). Additionally, biomechanical, biochemical, and histo-pathological studies further validated the results. Thus, it was concluded that protransfersome formulation has a great potential in providing better therapeutic efficacy of risedronate than its conventional counterpart.

Hyaluronate-functionalized hydroxyapatite nanoparticles laden with methotrexate and teriflunomide for the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA), an autoimmune inflammatory disorder is currently incurable. Methotrexate and Teriflunomide are routinely prescribed drugs but their uses are limited due to severe hepatotoxicity. Hyaluronic acid (HYA) is a targeting ligand for CD44 receptors overexpressed on inflamed macrophages. The present investigation aimed at design and fabrication of HYA coated hydroxyapatite nanoparticles (HA-NPs) loaded with Methotrexate (MTX) and Teriflunomide (TEF) (HAMT-NPs) to form HYA-HAMT-NPs for the treatment of RA. HYA-HAMT-NPs showed the nanoscale size of 274.9 ± 64 nm along with a zeta potential value of -26.80 ± 6.08 mV. FTIR spectra of HYA and HYA-HAMT-NPs proved the coating of HYA on HYA-HAMT-NPs. HYA-HAMT-NPs showed less cell viability compared to drugs on RAW 264.7 macrophage cells. A biodistribution study by gamma scintigraphy imaging further strengthened the results by revealing significantly higher (p<0.05) percentage radioactivity (76.76%) of HYA-HAMT-NPs in the synovial region. The results obtained by pharmacodynamic studies ensured the better efficacy of HYA-HAMT-NPs in preventing disease progression and promoting articular regeneration. Under hepatotoxicity evaluation, liver histopathology and liver enzyme assay revealed ~29% hepatotoxicity was reduced by HYA-HAMT-NPs when compared to conventional FOLITRAX-10 and AUBAGIO oral treatments. Overall, the results suggest that HYA-HAMT-NP is a promising delivery system to avoid drug-induced hepatotoxicity in RA.

Intranasal delivery of Naloxone-loaded solid lipid nanoparticles as a promising simple and non-invasive approach for the management of opioid overdose.

Naloxone is an opioid receptor antagonist that can eradicate all pre-indications of the toxicity and inverse the opioid overdose. However, oral administration of naloxone offers limitations such as its extensive first-pass metabolism that results in poor therapeutic effects. In order to resolve this issue, we developed intranasal solid-lipid nanoparticles in which naloxone was incorporated for the higher brain disposition of naloxone with superior therapeutic effects for the reversal of toxicity of opioid overdose. The preparation of naloxone loaded solid-lipid nanoparticles was done by employing the solvent evaporation method. Later, the designed formulation was optimized by Quality by Design approach, specifically, Box-Behnken method. The composition of optimized formulation was Glyceryl monostearate as a solid lipid (40 mg), Pluronic127 (0.5%) and Tween 80 (0.1%) as a surfactant and co-surfactant, respectively. Furthermore, the characterization of optimized formulation was achieved in terms of particle size, PDI, zeta potential, entrapment efficiency, and drug loading which were 190.2 nm, 0.082, -16 mV, 95 ± 0.532% and 19.08 ± 0.106%, respectively. Afterwards, in vitro, ex vivo and in vivo experiments were performed in which higher drug release and superior drug uptake by nasal membrane were observed for naloxone-loaded solid-lipid nanoparticles, later it was confirmed by confocal microscopy of ex vivo nasal membrane tissue. The findings of gamma scintigraphy investigation exhibited better deposition of naloxone-loaded solid-lipid nanoparticles as compared to naloxone solution. Also, the better deposition of naloxone by gamma scintigraphy was further validated by the investigation through the biodistribution study. Additionally, the key findings of the pharmacokinetic study revealed Cmax, Tmax, AUC0-t, AUC0-∞, T1/2 and Ke was found to be 163.95 ± 2.64 ng/ml, 240 ± 2.1 min, 17.75 ± 1.08 ng.hr/ml, 18.82 ± 2.51 ng.hr/ml, 70.71 ± 0.115 min, 0.098 ± 0.01 h-1 respectively. Lastly, investigations such as weight variation and histopathological proved the plausible potential of naloxone-loaded solid-lipid nanoparticles in terms of safety as no toxicity was noticed even after the administration of the three-folds dose of the normal dose. Therefore, considering all these findings, it could be easy to say that these developed naloxone-loaded solid-lipid nanoparticles could be administrated via intranasal route and can act as successful novel nanoformulation for the effective treatment of opioid overdose.