Design, optimization and characterization of atorvastatin loaded chitosan-based polyelectrolyte complex nanoparticles based transdermal patch.

AIM: Atorvastatin (ATO) loaded chitosan-based polyelectrolyte complex nanoparticles (PECN) incorporated transdermal patch was developed to enhance its skin permeability and bioavailability. METHODOLOGY: The ATO loaded PECN were prepared by ionic gelation method and optimized by Box-Behnken design. The optimized batches were evaluated for physicochemical characteristics, in vitro, ex vivo, cell line and stability studies. The optimized ATO-PECN were incorporated into transdermal patches by solvent evaporation method and evaluated for their physicochemical properties, ex vivo skin permeation, in vivo pharmacokinetics and stability study. RESULTS: The optimized batch of ATO-PECN had average size of 219.2 ± 5.98 nm with 82.68 ± 2.63 % entrapment and 25.41 ± 3.29 mV zeta potential. ATO-PECN showed sustained drug release and higher skin permeation. The cell line study showed that ATO-PECN increased the cell permeability of ATO as compared to ATO suspension. ATO-PECN loaded transdermal patch showed higher skin permeation. The in vivo pharmacokinetic study revealed that the ATO-PECN transdermal patch showed significant (p < 0.05) increase in pharmacokinetic parameters as compared to marketed oral tablet, confirming enhancement in bioavailability of ATO. CONCLUSIONS: The results of the present work concluded that the ATO-PECN loaded transdermal patch is a promising novel drug delivery system for poorly bioavailable drugs.

Fabrication and characterization of apremilast-loaded zinc oxide-mesoporous silica nanoparticles for psoriasis treatment.

Aim: The study was aimed to formulate and evaluate apremilast-loaded zinc oxide-mesoporous silica nanoparticles for treatment of psoriasis. Materials & methods: Mesoporous silica nanoparticles were prepared by using sol-gel method and evaluated for particle size, in vitro drug release, in vitro cytotoxicity study and in vivo pharmacodynamic study. Results: The synthesized mesoporous silica nanoparticles showed particle size of 319.9 ± 3.9 nm, with 24 ± 0.217% of loading capacity. In vitro cytotoxicity study on A-431 cell line showed increased anti-psoriatic activity of apremilast-loaded zinc oxide-mesoporous silica nanoparticles. In vivo pharmacodynamic study and histological studies showed improved efficacy of drug in imiquimod-induced psoriasis mice model. Conclusion: The apremilast-loaded zinc oxide-mesoporous silica nanoparticles showed improved therapeutic efficacy, suggesting that they are promising approach for topical treatment of psoriasis.

[Box: see text].

Glucagon: Delivery advancements for hypoglycemia management.

As the 100th anniversary of glucagon's discovery approaches, we reflect on the remarkable journey of understanding its pivotal role in glucose regulation. Advancements in glucagon delivery systems for managing hypoglycemia are unfolding with promise, albeit accompanied by formulation and implementation challenges. Recent developments include non-injectable methods like BAQSIMI® (Nasal glucagon) offers a user-friendly option, but stability, bioavailability, and rapid onset remain formulation hurdles. Closed-loop systems, combining glucagon with insulin, aim to automate glucose control, demanding stable and precise formulations compatible with complex algorithms. However, achieving co-delivery harmony and effective dual-hormone responses poses substantial challenges. Ogluo® and Gvoke HypoPen® are auto-injector pens, a ready-to-use solution that can rapidly control hypoglycemia and eliminate the need for mixing powder and liquid. GlucaGen® Hypokit® and Glucagon Emergency Kits are traditional deliveries that possess complexity during administration and are still widely used in clinical practice. In addition to this advancement, we have covered the recent patents and clinical trials of glucagon delivery. The synergy of patent innovation and clinical validation offers a glimpse into the transformative potential of glucagon delivery yet underscores the intricate path toward widespread adoption and improved diabetes care. Finally, this review will help the formulation scientist, clinicians, healthcare providers, and patient to manage hypoglycemia using glucagon.

Novel Discoveries and Clinical Advancements for Treating Onychomycosis: A Mechanistic Insight.

Onychomycosis continues to be the most challenging disease condition for pharmaceutical scientists to develop an effective drug delivery system. Treatment challenges lie in incomplete cure and high relapse rate. Present compilation provides cumulative information on pathophysiology, diagnostic techniques, and conventional treatment strategies to manage onychomycosis. Novel technologies developed for successful delivery of antifungal molecules are also discussed in brief. Multidirectional information offered by this article also unlocks the panoramic view of leading patented technologies and clinical trials. The obtained clinical landscape recommends the use of advanced technology driven approaches, as a promising way-out for treatment of onychomycosis. Collectively, present review warrants the application of novel technologies for the successful management of onychomycosis. This review will assist readers to envision a better understanding about the technologies available for combating onychomycosis. We also trust that these contributions address and certainly will encourage the design and development of nanocarriers-based delivery vehicles for effective management of onychomycosis.

Revisiting the in-vitro and in-vivo considerations for in-silico modelling of complex injectable drug products.

Complex injectable drug products (CIDPs) have often been developed to modulate the pharmacokinetics along with efficacy for therapeutic agents used for remediation of chronic disorders. The effective development of CIDPs has exhibited complex kinetics associated with multiphasic drug release from the prepared formulations. Consequently, predictability of pharmacokinetic modelling for such CIDPs has been difficult and there is need for advanced complex computational models for the establishment of accurate prediction models for in-vitro-in-vivo correlation (IVIVC). The computational modelling aims at supplementing the existing knowledge with mathematical equations to develop formulation strategies for generation of predictable and discriminatory IVIVC. Such an approach would help in reduction of the burden of effect of hidden factors on preclinical to clinical translations. Computational tools like physiologically based pharmacokinetics (PBPK) modelling have combined physicochemical and physiological properties along with IVIVC characteristics of clinically used formulations. Such techniques have helped in prediction and understanding of variability in pharmacodynamic parameters of potential generic products to clinically used formulations like Doxil®, Ambisome®, Abraxane® in healthy and diseased population using mathematical equations. The current review highlights the important formulation characteristics, in-vitro, preclinical in-vivo aspects which need to be considered while developing a stimulatory predictive PBPK model in establishment of an IVIVC and in-vitro-in-vivo relationship (IVIVR).

Nano-emulsomes for back of the eye delivery of Ganciclovir: formulation optimization, characterization & in vitro/in vivo evaluation.

In this work, novel carriers- nanoemulsomes (NE) of ganciclovir (GCV) and a fluorescent marker sodium fluorescein (SF) were developed and evaluated for posterior ocular delivery via topical route. GCV loaded emulsomes (GCV NE) were optimized by a factorial design and various characterization parameters were performed on the optimized batch. The optimized batch had particle size of 131.04 ± 1.87 nm, % entrapment efficiency of 36.42 ± 3.09% and its TEM image showed discrete spherical structures below 200 nm. Ocular irritation potential of excipients and formulation were evaluated by cell line based in vitro tests on SIRC cell line, results confirmed the safety of excipients for ocular use. Precorneal retention and pharmacokinetic studies of GCV NE were performed in rabbit eyes which showed significant retention of GCV NE in the cul-de-sac. The ocular distribution study of SF-loaded nanoemulsomes (SF NE) were performed in mice eyes by confocal microscopy, images showed fluorescence in the various internal layers of retina, suggesting efficacy of emulsomes in delivering agents to the back of eye via topical administration.

Development of Self-Microemulsifying Drug Delivery System to Improve Nisoldipine Bioavailability: Cell Line and In Vivo Evaluations : Development of Self-Microemulsifying Drug Delivery System.

The authors attempted to fabricate a novel lipid-based formulation of a lipophilic drug, nisoldipine (NISO). As NISO belongs to BCS class 2 drug, it suffers from low bioavailability (5%). Hence, the research was intended to ameliorate oral bioavailability of NISO via intestinal lymphatic transport. The NISO loaded self microemulsifying drug delivery system (SMEDDS) (NISO SMEDDS) was prepared using Peceol, Cremophor EL, and Transcutol HP. The Cremophor EL and Transcutol HP at 1:1 ratio showed maximum microemulsifying area, and average globule size was 16.78 ± 0.97 nm with PDI 0.121 ± 0.024. Cellular uptake studies (confocal microscopy and flow cytometry) using Caco-2 cells depicted higher fluorescence with coumarin-6 loaded SMEDDS as that of coumarin-6 solution which indicated deeper penetration. Mean fluorescence intensity (MFI) of coumarin-6 loaded SMEDDS was significantly improved (9.92-fold) in contrast to coumarin-6 solution. The NISO SMEDDS showed enhanced permeability (5.02 times) across Caco-2 cells compared to NISO suspension. The bioavailability improvement with NISO SMEEDS was 2.14 times relative to suspension, and lymphatic uptake was involved in oral absorption of NISO SMEDDS.

Triple negative breast cancer and non-small cell lung cancer: Clinical challenges and nano-formulation approaches.

Triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC) are amongst the most aggressive forms of solid tumors. TNBC is highlighted by absence of genetic components of progesterone receptor, HER2/neu and estrogen receptor in breast cancer. NSCLC is characterized by integration of malignant carcinoma into respiratory system. Both cancers are associated with poor median and overall survival rates with low progression free survival with high incidences of relapse. These cancers are characterized by tumor heterogeneity, genetic mutations, generation of cancer-stem cells, immune-resistance and chemoresistance. Further, these neoplasms have been reported for tumor cross-talk into second primary cancers for each other. Current chemotherapeutic regimens include usage of multiple agents in tandem to affect tumor cells through multiple mechanisms with various such combinations being clinically tested. However, lack of controlled delivery and effective temporospatial presence of chemotherapeutics has resulted in suboptimal therapeutic response. Consequently, passive targeted albumin bound paclitaxel and PEGylated liposomal doxorubicin have been clinically used and tested with newer drugs for improved therapeutic efficacy in these cancers. Active targeting of nanocarriers against surface overexpressed proteins in both neoplasms have been explored. However, use of single agent nanoparticulate formulations against both cancers have failed to elicit desired outcomes. This review aims to identify clinical unmet need in these cancers while establishing a correlation with tested nano-formulation approaches and issues with preclinical to clinical translation. Lipid and polymer-based drug-drug and drug-gene combinatorial nanocarriers delivering multiple chemotherapeutics simultaneously to desired site of action have been detailed. Finally, emerging opportunities such as pharmacological targets (immune check point and epigentic modulators) as well as gene-based modulation (siRNA/CRISPR/Cas9) and the nano-formulation challenges for effective treatment of both cancers have been explored.

Enhancement of bioavailability through transdermal drug delivery of paliperidone palmitate-loaded nanostructured lipid carriers.

Aim: The work describes enhanced bioavailability of paliperidone palmitate through transdermal delivery using nanostructured lipid carriers (NLC). Materials & methods: NLCs were formulated by nanoprecipitation method followed by incorporation in transdermal patch and physicochemical characterization. Results: NLCs showed high percentage entrapment efficiency of 83.44 ± 0.8%, drug loading of 24.75 ± 1.10% (w/w), particle size of 173.8 ± 3.25 nm, polydispersity index of 0.143 ± 0.05 and zeta potential of -15.9 ± 0.75 mV. In vitro and ex vivo studies indicated zero-order controlled drug release from NLCs and transdermal patch up to 48 h. Pharmacokinetic studies indicated 1.76-fold enhanced bioavailability by transdermal route as compared with oral drug delivery. Conclusion: From the results, it was concluded that drug-loaded NLCs-transdermal patch is promising drug delivery system for poorly bioavailable drugs.

An Overview of Nanocarrier-Based Adjuvants for Vaccine Delivery.

The development of vaccines is one of the most significant medical accomplishments which has helped to eradicate a large number of diseases. It has undergone an evolutionary process from live attenuated pathogen vaccine to killed whole organisms or inactivated toxins (toxoids), each of them having its own advantages and disadvantages. The crucial parameters in vaccination are the generation of memory response and protection against infection, while an important aspect is the effective delivery of antigen in an intelligent manner to evoke a robust immune response. In this regard, nanotechnology is greatly contributing to developing efficient vaccine adjuvants and delivery systems. These can protect the encapsulated antigen from the host's in-vivo environment and releasing it in a sustained manner to induce a long-lasting immunostimulatory effect. In view of this, the present review article summarizes nanoscale-based adjuvants and delivery vehicles such as viral vectors, virus-like particles and virosomes; non-viral vectors namely nanoemulsions, lipid nanocarriers, biodegradable and non-degradable nanoparticles, calcium phosphate nanoparticles, colloidally stable nanoparticles, proteosomes; and pattern recognition receptors covering c-type lectin receptors and toll-like receptors.

Formulation and clinical perspectives of inhalation-based nanocarrier delivery: a new archetype in lung cancer treatment.

Despite tremendous research in targeted delivery and specific molecular inhibitors (gene delivery), cytotoxic drug delivery through inhalation has been seen as a core part in the treatment of the lung cancer. Inhalation delivery provides a high dose of the drug directly to the lungs without affecting other body organs, increasing the therapeutic ratio. This article reviews the research performed over the last several decades regarding inhalation delivery of various cancer therapeutics for the treatment of lung cancer. Nevertheless, pulmonary administration of nanocarrier-based cancer therapeutics for lung cancer therapy is still in its infancy and faces greater than expected challenges. This article focuses on the current inhalable nanocarrier-based drugs for lung cancer treatment.

Stimuli responsive and receptor targeted iron oxide based nanoplatforms for multimodal therapy and imaging of cancer: Conjugation chemistry and alternative therapeutic strategies.

Cancer being one of the most precarious and second most fatal diseases evokes opportunities for multimodal delivery platforms which will act synergistically for efficient cancer treatment. Multifunctional iron oxide magnetic nanoparticles (IONPs) are being studied for few decades and still attracting increasing attention for several biomedical applications owing to their multifunctional design and intrinsic magnetic properties that provide a multimodal theranostic platform for cancer therapy, monitoring and diagnosis. The review article aims to provide brief information on various surface chemistries involved in modulating IONPs properties to exhibit potential therapy in cancer treatment. The review addresses structural, magnetic, thermal and optical properties of IONPs which aids in the fabrication of efficient multimodal nanoplatform in cancer therapy. The review discussed the pharmacokinetics of IONPs and attributes influencing them. This review inculcates recent advancements in therapies, focused on tumor-microenvironment-responsive and targeted therapy along with their eminent role in cancer diagnosis. The concept of stimuli-responsive including endogenous, exogenous and dual/multi stimuli-based delivery platform demonstrated significantly enhanced anticancer therapy. Several therapeutic approaches viz. chemotherapy, radiotherapy, immunotherapy, hyperthermia, gene therapy, sonodynamic therapy, photothermal, photodynamic-based therapy along with biosensing and several toxicity aspects of IONPs have been addressed in this review for effective cancer treatment.

Design and evaluation of hyaluronic acid-coated PLGA nanoparticles of raloxifene hydrochloride for treatment of breast cancer.

CONTEXT: In the present study, hyaluronic acid (HA)-coated raloxifene-loaded poly(l-lactic-co-glycolic acid) (PLGA) nanoparticles have been developed to improve the anticancer potential and reduce side effects associated with the drug. AIM AND OBJECTIVES: The investigation was aimed to formulate and optimize raloxifene hydrochloride (RALH)-loaded PLGA nanoparticles with surface modification using HA as a targeting moiety. To perform physicochemical characterization, in vitro cytotoxicity study (using MCF-7), in vitro drug release study and in vivo pharmacodynamic study of optimized formulation. METHODOLOGY: Raloxifene hydrochloride-loaded PLGA nanoparticles were prepared by nanoprecipitation technique, followed by surface modification with HA. Formulation was optimized by using 23 factorial design and characterized by physicochemical, in vitro drug release, in vitro cytotoxicity studies, and in vivo pharmacokinetics. RESULTS AND DISCUSSION: The particle size, PDI, zeta potential, entrapment efficiency, and loading capacity of spherically shaped RALH-loaded nanoparticles were 207.3 ± 4.2 d.nm, 0.218 ± 0.127, -.127 mV, 43.75 ± 1.2%, and 7.55 ± 1.14%, respectively. The in vitro drug release showed sustained release and followed Korsmeyer-Peppas model with non-Fickian release pattern. The in vitro cytotoxicity study of drug-loaded NPs by MTT assay on MCF-7 breast carcinoma cell showed anti-cancer activity after 48 h of treatment. CONCLUSION: The results of the present investigation suggested that RALH-loaded HA-modified PLGA nanoparticles showed sustained drug release with anticancer activity and can be a promising approach for treatment of breast cancer.

Topical instillation of triamcinolone acetonide-loaded emulsomes for posterior ocular delivery: statistical optimization and in vitro-in vivo studies.

The objective of the present investigation was to formulate and characterize a novel lipid-based carrier-emulsomes loaded with triamcinolone acetonide (TA)/Nile red (NR) for non-invasive delivery to the posterior segment of the eye upon topical application. To optimize and delineate the effect of independent variables on dependent variables, Box-Behnken design (BBD) was adopted. The optimized batch was characterized for size, zeta potential, surface morphology by transmission electron microscopy, drug-excipient interaction by differential scanning calorimetry, osmolarity, pH, ex vivo transcorneal permeation, and stability studies. A short-term exposure (STE) test was performed on Statens Seruminstitut Rabbit Corneal (SIRC) cell lines to evaluate the in vitro ocular irritation. Precorneal retention study was performed in rabbit eyes. Confocal microscopy was used for ocular distribution studies in mice eye by preparing dye (Nile red)-loaded formulations. The surface response and contour plots along with ANOVA results demonstrated an interaction between the factors. The optimized batch had particle size of 131.17 ± 3.17 nm and entrapment efficiency of 71.56 ± 4.19%. TEM image showed unimodal, nano-sized emulsomes. TA-loaded emulsomes exhibited higher transcorneal permeation as compared to drug solution. In vitro irritation studies confirmed the safety of excipients for ophthalmic use. Fluorescence microscopic images obtained after ocular distribution studies showed strong fluorescence in inner and outer plexiform layers of the retina in comparison to dye solution confirming the delivery of dye to the posterior segment of mice eye after topical ocular instillation. Graphical abstract.

Chondroitin sulfate conjugation facilitates tumor cell internalization of albumin nanoparticles for brain-targeted delivery of temozolomide via CD44 receptor-mediated targeting.

In the present investigation, temozolomide (TMZ) loaded chondroitin sulfate conjugated albumin nanoparticles (CS-TNPs) were fabricated by desolvation method were chondroitin sulfate (CS) was used as the surface exposed ligand to achieve CD44 receptor mediated targeting of brain tumor. The developed CS-TNPs were characterized for particle size, zeta potential, entrapment efficiency and drug loading and evaluated by FTIR, DSC, XRD and TEM analysis. BBB (blood brain barrier) passage study using in vitro BBB model indicated that CS-TNPs were able to efficiently cross the BBB. Cell viability assay data demonstrated higher cytotoxicity of CS-TNPs as compared with pure TMZ. The CD44 receptor blocking assay and receptor poisoning assay in U87 MG cells confirmed the CD44 receptor and endocytosis-mediated (caveolae pathway) uptake of CS-TNPs. CS-TNPs were able to generate ROS in U87 MG cells. In vivo pharmacokinetic and biodistribution studies were performed in Wistar rats. In vivo results revealed significant enhancement in pharmacokinetic profile of CS-TNPs as compared with TMZ alone. Biodistribution results demonstrated higher accumulation of TMZ in the brain by CS-TNPs as compared with the pure drug that confirmed the brain targeting ability of nanoparticles. From all obtained results, it may be concluded that CS-TNPs are promising carrier to deliver TMZ to the brain for targeted therapy of brain tumor. Graphical abstract.

Preparation and Surface Modification of Polymeric Nanoparticles for Drug Delivery: State of the Art.

Nanotechnology is one of the emerging fields in drug delivery for targeting the drug to the site of action. The polymeric nanoparticles as drug delivery systems have gained importance for the last few decades. They offer advantages over liposomes, dendrimers, emulsions etc. Surface engineering of polymeric nanoparticles is widely utilized to effectively target the cells in various diseases such as cancer, HIV infection. Surface modified nanoparticles offer various advantages such as targeted drug delivery, reduction in side effects, dose reduction and improved therapeutic efficacy. Moreover, they can aid in improving physical and biochemical properties, pharmacokinetic and pharmacodynamic profiles of the drug. Surface modified polymeric nanoparticles can provide targeted delivery of drugs into specific cells, especially when targets are intracellularly localized. This approach of surface modification would be more advantageous for the delivery of various anticancer, anti-inflammatory, anti-HIV drugs for more effective therapy. This review focuses on the techniques used for the fabrication of polymeric nanoparticles, the material used for surface modification and their applications.

Design and characterization of dual responsive mesoporous silica nanoparticles for breast cancer targeted therapy.

The main reason for limited efficacy of anticancer drug is the poor accretion of administered amount of drug within the tumor. Here, chitosan folate capped dual responsive mesoporous silica nanoparticles (MSNs) which can actively target cancer cells, and provide burst release of loaded anticancer drug within tumor cells and ultimately leading to improved therapeutic efficacy were synthesized. MSNs were synthesized using most economic silica source, sodium silicate. Doxorubicin (DOX) was loaded within the pores of MSNs and these drug loaded MSNs were first reacted with cystamine dihydrochloride followed by capping with chitosan-folate conjugate (CH-FA) to produce dual (redox and pH) responsive nanoparticles with the ability to actively target breast cancer cells. A triggered release of DOX from MSNs under acidic redox (pH 5.5, 10 mM GSH) environment was confirmed by in vitro release studies. The formulation exhibited 2.14 and 1.65 folds higher cytotoxicity than free drug against MCF-7 and MDA-MB-231 cells. DOX-MSN-SS-CH-FA showed superior tumor suppressing activity as compared to DOX-MSN or DOX alone in the treatment of Ehrlich Ascites Carcinoma (EAC) induced breast cancer with significantly reduced hematological and organ specific toxicities associated with DOX treatment.

Enhanced bioavailability and antihypertensive activity of nisoldipine loaded nanoemulsion: optimization, cytotoxicity and uptake across Caco-2 cell line, pharmacokinetic and pharmacodynamic studies.

Objective: The present study explored the antihypertensive activity of nisoldipine in oil in water nanoemulsion to improve its oral bioavailability via intestinal lymphatic uptake.Methods: Nanoemulsion was prepared by ultrasonication technique using Peceol, Cremophor EL and Transcutol HP as oil, surfactant and cosurfactant respectively. Optimization was done employing 32 full factorial design. The developed formulation was assessed for in vitro,cell line, ex vivo and in vivo studies.Results: The experimental results indicated homogeneity of the nanoemulsion with globule size of 62.35 ± 2.55 nm and PDI value of 0.108 ± 0.01 with negative zeta potential (-26.2 ± 3.6 mV). Transmission electron microscopy showed spherical oil globules morphology. The in vitro diffusion study showed significant increase in drug release from NE formulations (98.51 ± 2.64%) as compared to plain drug dispersion (29.73 ± 2.15%) in 0.1 N HCl + 0.5% SLS medium. Moreover, higher quantitative and qualitative uptake of nanoemulsion via Caco-2 cells showed superior intestinal absorption and improved therapeutic activity of nisoldipine when compared to drug dispersion. Pharmacokinetic and pharmacodynamic study confirmed significantly (p ˂ 0.05) greater bioavailability and antihypertensive activity of nisoldipine nanoemulsion when compared to its dispersion. These results are visualized in abstract figure.Conclusion: Thus, prepared nanoemulsion showed potential as oral delivery system for nisoldipine with superior oral bioavailability and therapeutic efficacy over drug dispersion.

Recent Advances in Drug Delivery Strategies for Improved Therapeutic Efficacy of Efavirenz.

BACKGROUND: Efavirenz, an anti-HIV agent, has a noticeable place in the HAART regimen for the treatment and maintenance therapy of AIDS. However, its poor water solubility accounts for hindered absorption and bio-distribution upon administration. This results in its low and variable bioavailability. To circumvent these limitations, various novel formulations of Efavirenz have been investigated in order to mitigate its drawbacks and draw out its maximum therapeutic effect. METHODS: Numerous formulations explored to overcome the drawbacks of Efavirenz include modified/ controlled-release tablets, solid dispersions, polymeric nanoparticles, dendrimers, surface-engineered nanoparticles and various other nanoformulations. Moreover, combinatorial formulations of Efavirenz with other Anti-HIV drugs have also been reported to overcome the problem of Drug-Resistance. RESULTS: The nanoformulation based strategies, owing to their ability to provide controlled release profile and targeted drug delivery were found to augment bioavailability, therapeutic efficacy and reduce the side effects of the Efavirenz. CONCLUSION: This review pivots around the challenges and recent advances in the delivery of Efavirenz with particular emphasis on novel formulations including its patents.

Self microemulsifying drug delivery system of lurasidone hydrochloride for enhanced oral bioavailability by lymphatic targeting: In vitro, Caco-2 cell line and in vivo evaluation.

The global aim of this research was to develop and evaluate self-microemulsifying drug delivery system (SMEDDS) to improve oral bioavailability of Lurasidone Hydrochloride (LH). A chylomicron flow blocking approach was used to evaluate lymphatic drug transport. The developed LH-SMEDDS was composed of Capmul MCM C8 (oil), Cremophor EL (surfactant) and Transcutol HP (co-surfactant). Highest microemulsifying area was obtained at 3:1 ratio (surfactant:cosurfactant) and mean globule size was found to be 49.22 ±â€¯1.60 nm. More than 98% drug release was obtained with LH-SMEDDS in phosphate buffer pH 6.8. Confocal microscopy and flow cytometry studies revealed higher fluorescence indicating deeper penetration across Caco-2 cells with Coumarin-6 SMEDDS as compared to Coumarin-6 solution. Mean Fluorescence Intensity (MFI) with Coumarin-6 loaded SMEDDS was increased 25.57 times with respect to Coumarin-6 solution. The permeability across Caco-2 cells was enhanced 3 times with LH-SMEDDS as compared to LH-suspension. Furthermore, Area Under Curve with LH-SMEDDS was found to be 2.92 times higher than that of LH suspension indicating improved bioavailability after formulating SMEDDS. Lymphatic transport in oral absorption of LH-SMEDDS was proved via lymphatic uptake study. All the findings suggest the effectiveness of lipid-based formulation i.e. SMEDDS of LH to augment the oral bioavailability via intestinal lymphatic pathway.