QbD-Assisted Development and Optimization of Doxycycline Hyclate- and Hydroxyapatite-Loaded Nanoparticles for Periodontal Delivery.

The current research aims to develop a carrier system for the delivery of a matrix metalloproteinase (MMP) inhibitor along with a bioceramic agent to the periodontal pocket. It is proposed that the present system, if given along with a systemic antibiotic, would be a fruitful approach for periodontitis amelioration. To fulfill the aforementioned objective, a doxycycline hyclate- and hydroxyapatite-adsorbed composite was prepared by a physical adsorption method and successfully loaded inside sodium alginate-chitosan nanoparticles and optimized based on particle size and drug content. Optimized formulation was then subjected to different evaluation parameters like encapsulation efficiency, hydroxyapatite content, ζ potential, surface morphology, in vitro drug release, cell line studies, and stability studies. For the optimized formulation, particle size, polydispersity index (PDI), entrapment efficiency, ζ potential, and drug content were found to be 336.50 nm, 0.23, 41.77%, -13.85 mV, and 14.00%, respectively. The surface morphology of the placebo and adsorbed composite-loaded nanoparticles as observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed the spherical shape and rough surface of the particles. In gingival crevicular fluid (GCF) 7.6, a sustained drug release profile was obtained up to 36 h. In vitro % viability studies performed on murine fibroblast cells (NIH3T3) and human periodontal ligament (hPDL) cell lines confirmed the proliferative nature of the formulation. Also, when subjected to stability studies for 4 weeks, particle size, PDI, and drug content did not vary considerably, thereby ensuring the stable nature of nanoparticles. Henceforth, sodium alginate-chitosan nanoparticles appeared to be a good carrier system for doxycycline hyclate and hydroxyapatite for periodontal therapy. If given along with a system antibiotic, the system will serve as a fruitful tool for infection-mediated periodontal regeneration and healing.

Utilization of Quince (Cydonia oblonga) Peel and Exploration of Its Metabolite Profiling and Cardioprotective Potential Against Doxorubicin-Induced Cardiotoxicity in Wistar Rats.

Quince (Cydonia oblonga Mill.) is a pomaceous fruit that is typically processed into jams, jellies, and marmalade. The byproduct, i.e., the quince peel emanated from the processing industry, can be upcycled, ensuring zero waste policy and resulting in a sustainable food system. In our study, the quince peel was explored for in vitro phytochemical analysis and in vivo cardioprotective potential. Two diverse extractions (ultrasonication and reflux) and four different solvents (aqueous, ethanolic, hydroethanolic, and methanolic) were used for the extraction of quince peel and assessed for the phytochemical and antioxidant study. Among all the evaluated extracts, hydroethanolic quince extract extracted through the reflux extraction method showed the maximum phenolic (27.23 ± 0.85 mg GAE/g DW) and flavonoid (16.5 ± 1.02 mg RE/g DW) content. The maximum antioxidant potential (DPPH) with an IC50 value of 204.8 ± 2.24 µg/mL was noted for the hydroethanolic extract. This best active extract was then subjected to HPTLC, UPLC-MS, mineral, and FTIR analysis to study the metabolic profiling and inorganic composition and to confirm the presence of bioactives. Additionally, the in vivo study was done in rats using doxorubicin (DOX)-induced cardiotoxicity. The rats were given extracts orally at 160 and 320 mg/kg bw for 30 days. ECG analysis was done at the termination of the experiment. Besides this, the lipid profile, blood serum parameters (CK-MB, LDH, AST), and tissue parameters (MDA, SOD, GSH, CAT) were analyzed. The DOX-treated group unveiled a substantial variance (p < 0.001) in all the parameters in contrast to the normal control group and extract control groups. However, the pretreated groups substantially alleviated the DOX-induced changes in all the parameters. Additionally, recuperation in histopathological alterations of the cardiac tissue in contrast to the DOX-induced toxicity was also seen in the pretreated groups. Thus, it could be said that the cardioprotective activity of the quince peel extract attributed to the presence of phytoconstituents counteracted the DOX-induced cardiotoxicity and assisted in the restoration of the cardiac injury in rats.

Development of Bedaquiline-Loaded SNEDDS Using Quality by Design (QbD) Approach to Improve Biopharmaceutical Attributes for the Management of Multidrug-Resistant Tuberculosis (MDR-TB).

Background: The ever-growing emergence of antibiotic resistance associated with tuberculosis (TB) has become a global challenge. In 2012, the USFDA gave expedited approval to bedaquiline (BDQ) as a new treatment for drug-resistant TB in adults when no other viable options are available. BDQ is a diarylquinoline derivative and exhibits targeted action on mycobacterium tuberculosis, but due to poor solubility, the desired therapeutic action is not achieved. Objective: To develop a QbD-based self-nanoemulsifying drug delivery system of bedaquiline using various oils, surfactants, and co-surfactants. Methods: The quality target product profile (QTPP) and critical quality attributes (CQAs) were identified with a patient-centric approach, which facilitated the selection of critical material attributes (CMAs) during pre-formulation studies and initial risk assessment. Caprylic acid as a lipid, propylene glycol as a surfactant, and Transcutol-P as a co-surfactant were selected as CMAs for the formulation of bedaquiline fumarate SNEDDS. Pseudo-ternary phase diagrams were constructed to determine the optimal ratio of oil and Smix. To optimize the formulation, a Box-Benkhen design (BBD) was used. The optimized formulation (BDQ-F-SNEDSS) was further evaluated for parameters such as droplet size, polydispersity index (PDI), percentage transmittance, dilution studies, stability studies, and cell toxicity through the A549 cell. Results: Optimized BDQ-F-SNEDDS showed well-formed droplets of 98.88 ± 2.1 nm with a zeta potential of 21.16 mV. In vitro studies showed enhanced drug release with a high degree of stability at 25 ± 2 °C, 60 ± 5% and 40 ± 2 °C, 75 ± 5%. Furthermore, BDQ-F-SNEDDS showed promising cell viability in A549 cells, indicating BDQ-F-SNEDDS as a safer formulation for oral delivery. Conclusion: Finally, it was concluded that the utilization of a QbD approach in the development of BDQ-F-loaded SNEDDS offers a promising strategy to improve the biopharmaceutical properties of the drug, resulting in potential cost and time savings.

Dasatinib: a potential tyrosine kinase inhibitor to fight against multiple cancer malignancies.

Dasatinib is the 2nd generation TKI (Tyrosine Kinase Inhibitor) having the potential to treat numerous forms of leukemic and cancer patients and it is 300 times more potent than imatinib. Cancer is the major cause of death globally and need to enumerate novel strategies to coping with it. Various novel therapeutics introduced into the market for ease in treating various forms of cancer. We reviewed and evaluated all the related aspects of dasatinib, which can enhance the knowledge about dasatinib therapeutics methodology, pharmacodynamic and pharmacokinetics, side effects, advantages, disadvantages, various kinds of interactions and its novel formulations as well.

Precision engineering designed phospholipid-tagged pamidronate complex functionalized SNEDDS for the treatment of postmenopausal osteoporosis.

Disodium pamidronate, a second-generation bisphosphonate is a potent drug for the treatment of osteoporosis, which has been very well established by previous literature. It has very low oral permeability, leading to its low oral bioavailability, which restrict this drug to being administered orally. Therefore, the present research work includes the development of an orally effective nanoformulation of pamidronate. In this work, disodium pamidronate was complexed with phospholipon 90G for the enhancement of permeability and to investigate the phospholipon 90G-tagged pamidronate complex-loaded SNEDDS for oral delivery with promises of enhanced bioavailability and anti-osteoporotic activity. The rational design and optimization was employed using Central Composite Design (Design Expert® 12, software) to optimize nanoformulation parameters. In this work, a commercially potential self nano-emulsifying drug delivery system (SNEDDS) has been developed and evaluated for improved oral bioavailability and better clinical acceptance. The hot micro-emulsification and ultracentrifugation method with vortex mixing was utilized for effective tagging of phospholipon 90G with pamidronate and then loading into the SNEDDS nanocarrier. The optimized Pam-PLc SNEDDS formulation was characterized for particle size, PDI, and zeta potential and found to be 56.38 ± 1.37 nm, 0.218 ± 0.113, and 22.41 ± 1.14 respectively. Also, a 37.9% improved bioavailability of pamidronate compared to marketed tablet was observed. Similarly, in vivo pharmacokinetic studies suggest a 31.77% increased bone density and significant enhanced bone biomarkers compared to marketed tablets. The developed formulation is safe and effectively overcomes anti-osteoporosis promises with improved therapeutic potential. This work provides very significant achievements in postmenopausal osteoporosis treatment and may lead to possible use of nanotherapeutic-driven emerging biodegradable carriers-based drug delivery.

Recent update on electrospinning and electrospun nanofibers: current trends and their applications.

Electrospinning is a versatile and viable technique for generating ultrathin fibers. Remarkable progress has been made in techniques for creating electro-spun and non-electro-spun nanofibers. Nanofibers were the center of attention for industries and researchers due to their simplicity in manufacture and setup. The review discusses a thorough overview of both electrospinning and non-electrospinning processes, including their setup, fabrication process, components, and applications. The review starts with an overview of the field of nanotechnology, the background of electrospinning, the surge in demand for nanofiber production, the materials needed to make nanofibers, and the critical process variables that determine the characteristics of nanofibers. Additionally, the diverse applications of electrospun nanofibers, such as smart mats, catalytic supports, filtration membranes, energy storage/heritage components, electrical devices (batteries), and biomedical scaffolds, are then covered. Further, the review concentrates on the most recent and pertinent developments in nanofibers that are connected to the use of nanofibers, focusing on the most illustrative cases. Finally, challenges and their possible solutions, marketing, and the future prospects of nanofiber development are discussed.

Additive Manufacturing and Printing Approaches for the Development of Pharmaceutical Dosage Forms with Improved Biopharmaceutical Attributes.

The pharmaceutical industry is moving towards the future and is witnessing innovation in drug development through the introduction of personalized medicine technologies. Instead of adapting the dose thata patient needs, they were adapted to the manufacturer's dose. Nowpatient-specific or customized dosing methods and dosing combinations have superior persistence to the standard mass-produced drugs. Printing technology has gained interest during the last few years to manufacture personalized dosage forms. For manufacturing personalized drug products, three-dimensional printing (3DP) has expanded to the pharmaceutical industry. With the approval of the first 3DP product, an unprecedented opportunity for discovering new compounds and technologies has arisen. This article has re-evaluated various printing technology and theirutilization in personalized medicines. Further, we also discussed its history, advantages, challenges and differenttypes of printing technologies with advantages and limitations, particularly in the area of pharmaceutical research.

Nano Matrix Soft Confectionary for Oral Supplementation of Vitamin D: Stability and Sensory Analysis.

Vitamin D deficiency distresses nearly 50% of the population globally and multiple studies have highlighted the association of Vitamin D with a number of clinical manifestations, including musculoskeletal, cardiovascular, cerebrovascular, and neurological disorders. In the current study, vitamin D oil-in-water (O/W) nanoemulsions were developed and incorporated in edible gummies to enhance bioavailability, stability, and patient compliance. The spontaneous emulsification method was employed to produce a nano-emulsion using corn oil with tween 20 and lecithin as emulsifiers. Optimization was carried out using pseudo-ternary phase diagrams and the average particle size and polydispersity index (PDI) of the optimized nanoemulsion were found to be 118.6 ± 4.3 nm and 0.11 ± 0.30, respectively. HPLC stability analysis demonstrated that the nano-emulsion prevented the degradation and it retained more than 97% of active vitamin D over 15 days compared to 94.5% in oil solution. Similar results were obtained over further storage analysis. Vitamin D gummies based on emulsion-based gelled matrices were then developed using gelatin as hydrocolloid and varying quantities of corn oil. Texture analysis revealed that gummies formulated with 10% corn oil had the optimum hardness of 3095.6 ± 201.7 g on the first day which remained consistent on day 45 with similar values of 3594.4 ± 210.6 g. Sensory evaluation by 19 judges using the nine-point hedonic scale highlighted that the taste and overall acceptance of formulated gummies did not change significantly (p > 0.05) over 45 days storage. This study suggested that nanoemulsions consistently prevent the environmental degradation of vitamin D, already known to offer protection in GI by providing sustained intestinal release and enhancing overall bioavailability. Soft chewable matrices were easy to chew and swallow, and they provided greater patient compliance.

Cannabis as a potential compound against various malignancies, legal aspects, advancement by exploiting nanotechnology and clinical trials.

Various preclinical and clinical studies exhibited the potential of cannabis against various diseases, including cancer and related pain. Subsequently, many efforts have been made to establish and develop cannabis-related products and make them available as prescription products. Moreover, FDA has already approved some cannabis-related products, and more advancement in this aspect is still going on. However, the approved product of cannabis is in oral dosage form, which exerts various limitations to achieve maximum therapeutic effects. A considerable translation is on a hike to improve bioavailability, and ultimately, the therapeutic efficacy of cannabis by the employment of nanotechnology. Besides the well-known psychotropic effects of cannabis upon the use at high doses, literature has also shown the importance of cannabis and its constituents in minimising the lethality of cancer in the preclinical models. This review discusses the history of cannabis, its legal aspect, safety profile, the mechanism by which cannabis combats with cancer, and the advancement of clinical therapy by exploiting nanotechnology. A brief discussion related to the role of cannabinoid in various cancers has also been incorporated. Lastly, the information regarding completed and ongoing trials have also been elaborated.

Mupirocin-Loaded Chitosan Microspheres Embedded in Piper betle Extract Containing Collagen Scaffold Accelerate Wound Healing Activity.

This study reports the formulation of mupirocin-loaded chitosan microspheres embedded in Piper betle extract containing collagen scaffold as combinational drug delivery for improved wound healing. Selection of chitosan type (molecular weight and degree of deacetylation) was carried out based on their antibacterial efficacy. The low molecular weight chitosan was selected owing to the highest antibacterial action against gram-positive as well as gram-negative bacteria. Low molecular weight chitosan-microspheres showed spherical shape with largely smooth surface morphology, 11.81% of mupirocin loading, and its controlled release profile. The XRD, DSC thermograms, and FT-IR spectral analysis revealed the mupirocin loaded in molecularly dispersed or in amorphous form, and having no chemical interactions with the chitosan matrix, respectively. The in vivo study indicates potential effect of the mupirocin, Piper betle, and chitosan in the collagen scaffold in the wound healing efficiency with approximately 90% wound healing observed at the end of 15 days of study for combinational drug-loaded chitosan microspheres-collagen scaffold-treated group. The histopathology examination further revealed tissue lined by stratified squamous epithelium, collagen deposition, fibroblastic proliferation, and absence of inflammation indicating relatively efficient wound healing once treated with combinational drug-loaded chitosan microspheres containing scaffold.

A Validated, Rapid and Cost-Efficient HPTLC Method for Quantification of Gamma-Linolenic Acid in Borage Oil and Evaluation of Antioxidant Activity.

Borage oil that is extracted from (Borago officinalis Linn.) is a well-known medicinal plant having various medicinal benefits. In this work, an affordable, simple, reliable, rapid and easily accessible high-performance thin-layer chromatography (HPTLC) method was developed for the estimation of gamma-linolenic acid (GLA) in borage oil. HPTLC method employs thin-layer chromatography (TLC) aluminum plates precoated with silica gel (G60F254) as the stationary phase, and the mixture of hexane:toulene:glacial acetic acid (3:7:1, v/v/v) was used as the mobile phase. Densitometric analysis of the TLC plates was carried out at 200 nm. The developed method showed well-resolved spots with retention factor (Rf) value of 0.53 ± 0.04 for GLA. Various experimental conditions like saturation time for chamber, solvent phase migration and width of the band were studied intensely for selecting the optimum conditions. The method validation was performed for parameters like linearity, accuracy, specificity and precision. The values of limit of detection and limit of quantification for GLA were found to be 0.221 and 0.737 µg/band, respectively. In nutshell, the developed HPTLC method was found to be highly sensitive for the estimation of GLA in the herbal oil samples and formulations.

Repurposing pentosan polysulfate sodium as hyaluronic acid linked polyion complex nanoparticles for the management of osteoarthritis: A potential approach.

Osteoarthritis is still a disease burden for pharmaceutical scientists and strategy makers. It is associated with the chronic inflammation of joints especially weight-bearing joints like knee, hip, backbone, and phalanges. NSAIDs that are used for the management of inflammation associated with osteoarthritis have high side effects related to gastric upset, gastric ulcer, and long term treatment associated with liver and kidney damage. Nanotechnology has gained a huge scope for the management of arthritis as it can reach out to the deep inside the cell and alter cellular physiology as desired. The present study hypothesizes the use of polyion complex nanoparticles of hyaluronic acid linked Pentosan polysulfate sodium, a disease-modifying agent for the treatment of osteoarthritis administered through transdermal route. The hypothesis involves the use of drug repurposing as the drug was initially approved for interstitial cystitis, a condition of the urinary bladder associated with pain and swelling. Being very low oral bioavailability and gastric irritation profile, the transdermal route would be beneficial. To overcome the problem associated with the oral route, there is a need for the targeted approach that will particularly reach at inflammatory sites. Thereby transdermal delivery of hyaluronic acid linked Pentosan polysulfate sodium through polyion complex nanoparticle therapy will be a novel therapeutic approach to combat osteoarthritis.

Recent Advances in Targeted Drug Delivery Approaches Using Lipidic and Polymeric Nanocarriers for the Management of Alzheimer's Disease.

Drug delivery to the brain has been a significant challenge in treating neurodegenerative disorders such as Alzheimer's disease due to the presence of the blood-brain barrier, which primarily obstructs the access of drugs and biomolecules into the brain. Several methods to overcome the blood-brain barrier have been employed, such as chemical disruption, surgical intervention, focused ultrasound, intranasal delivery, and the use of nanocarriers. Nanocarrier systems remain the method of choice and have shown promising results over the past decade to achieve better drug targeting. Polymeric nanocarriers and lipidic nanoparticles act as a carrier system providing better encapsulation of drugs, site-specific delivery, increased bioavailability, and sustained release of drugs. The surface modifications and functionalization of these nanocarrier systems have greatly facilitated targeted drug delivery. The safety and efficacy of these nanocarrier systems have been ascertained by several in vitro and in vivo models. In the present review, we have elaborated on recent developments of nanoparticles as a drug delivery system for Alzheimer's disease, explicitly focusing on polymeric and lipidic nanoparticles.

Recent update of 3D printing technology in pharmaceutical formulation development.

In modern world, Pharma sector observes steep increase in demand of personalized medicine. Various unique ideas and technology were proposed and implemented by different researchers to prepare personalized medicine and devices. 3-dimensional printing (3DP) is one of the revolutionary technologies which can be used to prepare tailored medicine via CAD (Computer Aided Design) software. 3DP allows researchers to manufacture customized dosage form with desired modifications in geometry which would in turn alter dosage behaviour of the product with reduced side effects. Current achievement of 3DP includes personalized and adjustable dosage form, multifunction drug delivery systems, medical devices, phantoms, and implants specific to patient anatomy. Additionally, 3DP is employed for preparing tailored regenerative medicines. This review focuses on 3DP use in pharmaceuticals including drug delivery systems and medical devices with their method of fabrication. Additionally, different clinical trials as well as different patents done till date are cited in the paper. Furthermore, regulatory issues and future perspective related to 3 D printing is also well discussed.

Development of a Loop-mediated isothermal amplification (LAMP) technique for specific and early detection of Mycobacterium leprae in clinical samples.

Leprosy, a progressive, mutilating and highly stigmatized disease caused by Mycobacterium leprae (ML), continues to prevail in the developing world. This is due to the absence of rapid, specific and sensitive diagnostic tools for its early detection since the disease gets notified only with the advent of physical scarring in patients. This study reports the development of a Loop-mediated isothermal amplification (LAMP) technique for fast, sensitive and specific amplification of 16S rRNA gene of ML DNA for early detection of leprosy in resource-limited areas. Various parameters were optimized to obtain robust and reliable amplification of ML DNA. Blind clinical validation studies were performed which showed that this technique had complete concurrence with conventional techniques. Total absence of amplification of negative control DNA confirmed the specificity of this test. Various visual detection methods viz. colorimetric, turbidity differentiation and bridge flocculation were standardized to establish easy-to-read and rapid diagnosis. This technique eliminates the lack of accuracy and sensitivity in skin smear tests in patients and the requirement for expensive lab equipments and trained technicians. The technique holds promise for further expansion and has the potential to cater to the unmet needs of society for a cheap, highly-sensitive and robust rapid diagnosis of ML.

Nanostructured Therapeutic Systems of PUFAs for the Treatment of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is a typical category of the most common and aggressive brain tumors, with a high incidence in older adults, particularly in males. Although the etiology of GBM has not been fully elucidated, yet it is characterized by highly proliferative activity in the glial cells. Its complete resection is impossible, and radiotherapy is not always efficient for complete relief. Thus, GBM remains a therapeutic challenge in neurooncology as there is no treatment that provides significant improvement in the survival rate of patients. In this regard, the identification of newer drug therapy for the treatment of GBM is gaining popularity. However, identifying new targets and developing new leads for screening suitable drug candidates require the investment of resources like time, money, and efforts. It has been observed in many research studies that the use of polyunsaturated fatty acids (PUFAs) as therapeutic moieties for cancer treatment has yielded significant interest owing to their cost-effective availability, limited side effects, and insensitivity towards drug resistance. Nevertheless, the implications of nanostructured therapeutic systems in delivering the PUFAs can provide significant improvement in their biopharmaceutical performance and antitumor activity over the existing alkylating agents used as chemotherapeutic drugs in GBM. Currently, various studies have shown that PUFAs, especially γ-linolenic acid (GLA), have selective tumoricidal action and the ability to reduce antioxidant contents of the glioma tumor cells. In this regard, the present review endeavors to provide an insight into the applications of nanomedicinal drug carriers used for delivering the PUFAs for the effective treatment of GBM and associated diseases.

Novel therapeutic interventions in cancer treatment using protein and peptide-based targeted smart systems.

Cancer, being the most prevalent and resistant disease afflicting any gender, age or social status, is the ultimate challenge for the scientific community. The new generation therapeutics for cancer management has shifted the approach to personalized/precision medicine, making use of patient- and tumor-specific markers for specifying the targeted therapies for each patient. Peptides targeting these cancer-specific signatures hold enormous potential for cancer therapy and diagnosis. The rapid advancements in the combinatorial peptide libraries served as an impetus to the development of multifunctional peptide-based materials for targeted cancer therapy. The present review outlines benefits and shortcomings of peptides as cancer therapeutics and the potential of peptide modified nanomedicines for targeted delivery of anticancer agents.

99mTc-Methionine Gold Nanoparticles as a Promising Biomaterial for Enhanced Tumor Imaging.

Methionine-gold nanoparticles (MGNs) was synthesized by conjugating methionine via dithiocarbamate linkage to gold nanoparticles (GNPs), prepared simultaneously by one pot modified Burst method. Formation of MGNs was confirmed by UV-visible spectroscopy and appearance of new IR bands in the range of 934 cm-1 to 1086 cm-1 and shifting of N-C,S-S and S-C-S stretching, confirms the involvement of '-S-C-S-' group of methionine dithiocarbamate with GNPs. The presence of Au in MGNs was confirmed by EDXA spectrum, whereas TEM, SAED and XRD revealed that MGNs are nanocrystalline (~13 nm) and have face-centered cubic structure. MGNs was labeled with 99mTc (TMGNs) with radiolabeling efficiency greater than 99% using 300 µg of stannous chloride, pH 7 and 90.6 MBq of 99mTcO4. The stability data showed that the conjugate will remain infrangible in systemic circulation and in acidic microenvironment of tumor. The blood kinetic profile of TMGN in rabbits and biodistribution studies in EAT tumor bearing balb/c mice showed longer in vivo circulation and slow clearance compared to radiolabeled methionine (TM). TMGN demonstrated nearly three-fold higher tumor accumulation (3.9 ± 0.35% ID/g), 2-fold lower tumor saturation dose (1.0 µg/kg) and higher tumor retention compared with TM. Data showed that the TMGN tumor: blood ratio (1.05) is nearly 2.5-fold higher than TM (0.44), whereas TMGN tumor: muscle ratio (97.5) is nearly 8-fold higher than TM (11.6). In conclusion, TMGN showed excellent tumor targeting and has promising prospects as a SPECT-radiopharmaceutical for imaging tumors.

Parenteral Sustained Release Lipid Phase-Transition System of Ziprasidone: Fabrication and Evaluation for Schizophrenia Therapy.

INTRODUCTION: Ziprasidone (ZP) is a novel atypical antipsychotic agent effective in the treatment of positive and negative symptoms of schizophrenia with low chances for extrapyramidal side effects (EPs) and cognitive deficits. ZP possesses poor oral bioavailability (~50%), short biological half-life (~2.5 h) and due to extensive first-pass metabolism, a repeated dose is administered which makes the therapy non-adherent, leading to patient non-compliance. Therefore, this is a first report of developing parenteral ZP loaded sustained release phospholipid based phase-transition system (ZP-LPS). METHODS: The ZP-LPS system was formulated by mixing of biocompatible materials including phospholipid E 80, medium chain triglyceride (MCT) and ethanol. Optimization was done by aqueous titration method using pseudo-ternary phase diagram and dynamic rheological measurements. In vivo depot formation was confirmed by gamma scintigraphy after subcutaneous injection. Biodegradation and biocompatibility studies were performed for its safety evaluation. Finally, the efficacy of the formulation was assessed by Morris water maze (MWM) test and dizocilpine (MK-801) was used to induce schizophrenia in Sprague-Dawley rats. RESULTS: Optimized ZP-LPS showed rapid gelation (2 min), highest change in viscosity (~48000 mPa.s) and sustained release of ZP over a period of 1 month. Gamma scintigraphy depicted that the low-viscosity ZP-LPS system undergo rapid in situ gelation. Biodegradation and biocompatibility studies revealed gradual degradation in size of depot over a period of 28 days without any inflammation at the injection site. In MWM test, escape latency, time spent and total distance in target quadrant were significantly improved (p < 0.001) in the ZP-LPS group in comparison to the MK-801 group when evaluated at day 0, day 7 and day 28. However, significant improvement (p < 0.001) was observed only at day 0 in ZP suspension group. CONCLUSION: The overall result indicates that the novel ZP-LPS system is safe, biodegradable, and effective for the management of schizophrenia.