QbD Enabled Development and Evaluation of Pazopanib Loaded Nanoliposomes for PDAC Treatment.

Pancreatic ductal adenocarcinoma (PDAC) is one of the highly fatal types of cancer with high mortality/incidence. Considering the crucial role of vascular endothelial growth factor (VEGF) in PDAC progression, its inhibition can be a viable strategy for the treatment. Pazopanib, a second-generation VEGF inhibitor, is approved for the treatment of various oncological conditions. However, due to associated limitations like low oral bioavailability (14-39%), high inter/intra-subject variability, stability issues, etc., high doses (800 mg) are required, which further lead to non-specific toxicities and also contribute toward cancer resistance. Thus, to overcome these challenges, pazopanib-loaded PEGylated nanoliposomes were developed and evaluated against pancreatic cancer cell lines. The nanoliposomes were prepared by thin-film hydration method, followed by characterization and stability studies. This QbD-enabled process design successfully led to the development of a suitable pazopanib liposomal formulation with desirable properties. The % entrapment of PZP-loaded non-PEGylated and PEGylated nanoliposomes was found to be 75.2% and 84.9%, respectively, whereas their particle size was found to be 129.7 nm and 182.0 nm, respectively. The developed liposomal formulations exhibited a prolonged release and showed desirable physicochemical properties. Furthermore, these liposomal formulations were also assessed for in vitro cell lines, such as cell cytotoxicity assay and cell uptake. These studies confirm the effectiveness of developed liposomal formulations against pancreatic cancer cell lines. The outcomes of this work provide encouraging results and a way forward to thoroughly investigate its potential for PDAC treatment.

Dynamic intervention to enhance the stability of PEGylated Ibrutinib loaded lipidic nano-vesicular systems: transitioning from colloidal dispersion to lyophilized product.

Liposomes being a promising colloidal system facilitates delivery of drugs with limited pharmacokinetic properties to achieve desirable clinical applications. However, development of a stable liposomal system is always challenging due to multiple complexities involved. Aqueous instability of liposomes and impact of various process and formulation parameters can lead to serious alteration of its therapeutic performance. In the proposed work, the authors aim to develop stable Ibrutinib-loaded liposomes using lyophilization and Quality-by-Design and assess their long-term stability. Ibrutinib-loaded liposomes were developed and optimized using Quality-by-Design technique and were further PEGylated and characterized for the same. Effect of cryoprotectants during lyophilization and other parameters are evaluated to obtain a robust formulation. The stability studies were conducted upto 6 months at various storage conditions to evaluate the effect of lyophilization. The impact of formulation, processing and lyophilization parameters on physicochemical properties of developed liposomal systems were evaluated and are critically discussed. Liquid dispersion exhibited a %degradation of 16-36% at 25 °C/60% RH which was reduced for less than 1% in lyophilized formulation for 6 months. Critical analysis and assessment of various parameters lead to identification of optimum conditions to manufacture this drug product and also opens way forward for further evaluation and translational possibilities.

Biopolymer zein nanoparticles loaded with Moringa Oleifera extract for improved wound healing activity: Development, Qbd based optimization and in vivo study.

Recently, nanobiomaterials have been explored for improved biological activities and value addition to the herbal extracts. Zein is a natural biopolymer with excellent pharmaceutical characteristics for topical applications. Moringa oleifera plant possesses large number of phytopharmaceuticals and its leaves are used in wound healing since ancient time. In this study, we studied first time, encapsulation of Moringa oleifera leaves aqueous extract into zein nanoparticles which are developed and optimized using quality by design approach. Moringa oleifera leaves aqueous extract was characterized by FTIR and total phenolic content determination. Moringa oleifera leaves aqueous extract loaded zein nanoparticles were systematically characterized for particle size, PDI, zeta potential, transmission electron microscopy and loading capacity. Further, a gel having optimized formulation for topical application was prepared and characterized for pH, spreadability, extrudability and storage stability. The so developed formulation were tested for wound healing activities on animals and results clearly indicated significant activity (p < 0.05) in case of Moringa oleifera leaves aqueous extract loaded zein nanoparticles formulation than control and relatively improved wound healing than Moringa oleifera leaves aqueous extract only loaded gel . This study opens up new possibilities in exploring zein nanoparticles for herbal extract based therapeutic applications.

Current Scenario and Future Prospects of Adverse Drug Reactions (ADRs) Monitoring and Reporting Mechanisms in the Rural Areas of India.

BACKGROUND: Pharmacovigilance (PV) deals with the detection, collection, assessment, understanding, and prevention of adverse effects associated with drugs. The objective of PV is to ensure the safety of the medicines and patients by monitoring and reporting all adverse drug reactions (ADRs) associated with prescribed medicine usage. Findings have indicated that about 0.2- 24% of hospitalization cases are due to ADRs, of which 3.7% of patients have lethal ADRs. The reasons include the number of prescribed drugs, an increased number of new medicines in the market, an inadequate PV system for ADR monitoring, and a need for more awareness and knowledge about ADR reporting. Severe ADRs lead to enhanced hospital stays, increased treatment costs, risk of death, and many medical and economic consequences. Therefore, ADR reporting at its first instance is essential to avoid further harmful effects of the prescribed drugs. In India, the rate of ADR reporting is less than 1%, whereas worldwide, it is 5% due to a need for more awareness about PV and ADR monitoring among healthcare providers and patients. The main objective of this review is to highlight the current scenario and possible futuristic ways of ADR reporting methods in rural areas of India. We have searched the literature using PubMed, Google scholar, Indian citation index to retrieve the resources related to ADR monitoring and reporting in India's urban and rural areas. Spontaneous reporting is the most commonly used PV method to report ADRs in India's urban and rural areas. Evidence revealed that no effective ADR reporting mechanisms developed in rural areas causing underreporting of ADR, thus increasing the threat to the rural population. Hence, PV and ADR reporting awareness among healthcare professionals and patients, telecommunication, telemedicine, use of social media and electronic medical records, and artificial intelligence are the potential approaches for prevention, monitoring, and reporting of ADRs in rural areas.

Multifunctional nanotherapeutics for intracellular trafficking of doxorubicin against breast cancer.

Aims: To develop an estrone-targeted d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS)-based liposomal system for enhanced intracellular delivery of doxorubicin (DOX). Materials & methods: Zetasizer, transmission electron microscopy, energy dispersive x-ray, Fourier-transform infrared spectroscopy, differential scanning calorimetry, x-ray diffraction, confocal laser scanning microscopy and FACS analysis were used for formulation characterization and evaluation. Results: The DOX-LIPO-TPGS and DOX-LIPO-TPGS-estrone formulations had vesicle sizes (117.6 ± 3.51; 144 ± 5.00 nm), zeta potential (-36.4 ± 0.75; -35.8 ± 0.76), polydispersity index (0.123 ± 0.005; 0.169 ± 0.005) and percent entrapment efficiency (73.56 ± 3.55; 77.16 ± 3.83%) with improved cytotoxicity and cellular uptake, confirming the targeted potential of the developed formulations. Conclusion: The results suggest that the developed liposomal formulation with desired characteristics is potentially capable of nonimmunogenic, site-specific drug delivery to targeted cancer sites and reduced DOX-associated cardiac toxicity.

Doxorubicin (DOX) is an effective chemotherapy drug to treat breast cancer. However, DOX can cause unwanted side effects such as damage to the heart. This is due to side effects in healthy body tissues. This study was designed to develop nanoparticles that target cancer cells specifically to improve the delivery of DOX to these cells and prevent side effects elsewhere. Nanoparticles called liposomes were used as the platform for delivering DOX. Liposomes are sometimes coated with d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS), a synthetic vitamin D derivative. This helps the liposome evade the immune system and release the drug more effectively. TPGS was tethered with estrone (ES), a type of estrogen. Certain breast cancer cells have many more estrogen receptors on their cell surface than healthy cells. TPGS-ES was coated on DOX-loaded liposomes to achieve enhanced intracellular delivery of DOX to breast cancer cells specifically. These liposomes were called DOX-LIPO-TPGS-ES. This liposome proved more toxic to cells in a breast cancer cell line than free DOX or liposomes without tethered ES. When tested in rats, DOX-LIPO-TPGS-ES showed increased tumor uptake compared with free DOX or liposomes without tethered ES. Rats treated with either liposomal drug showed normal levels of key markers associated with heart function, whereas those treated with free DOX showed increased levels of these markers. These results suggest that DOX-LIPO-TPGS-ES is capable of highly targeted delivery of DOX with limited side effects.

Lentinan: An unexplored novel biomaterial in drug and gene delivery applications.

Recently, lentinan (LNT) has been utilized for its diversified potential in research with an extended role from nutritional or medicinal applications to a novel biomaterial. LNT is a biocompatible, multifunctional polysaccharide employed as a pharmaceutical additive in engineering customized drug or gene carriers with an improved safety profile. Its triple helical structure containing hydrogen bonding offers more extraordinary binding sites for the attachments of dectin-1 receptors and polynucleotide sequences (poly(dA)). Hence, the diseases expressing dectin-1 receptors can be specifically targeted through so-designed LNT-engineered drug carriers. Gene delivery using poly(dA)-s-LNT complexes and composites has exhibited greater targetability and specificity. The achievement of such gene applications is assessed through the pH and redox potential of the extracellular cell membrane. The steric hindrance-acquiring behavior of LNT shows promise as a system stabilizer in drug carrier engineering. LNT shows viscoelastic gelling behavior temperature-dependently and therefore needs to explore more to meet topical disease applications. The immunomodulatory and vaccine adjuvant properties of LNT help in mitigating viral infections too. This review highlights the new role of LNT as a novel biomaterial, particularly in drug delivery and gene delivery applications. In addition, its importance in achieving various biomedical applications is also discussed.

Exploring potential of diacerin nanogel for topical application in arthritis: Formulation development, QbD based optimization and pre-clinical evaluation.

Diacerein (DCN) is a chondroprotective agent which shows inadequate oral bioavailability along with gastrointestinal side effects. This study is intended to develop a topical novel DCN delivery system. DCN nanogel was prepared by emulsion solvent diffusion technique. The formulation was optimized by response surface methodology by taking two independent variables, concentration of carbopol 940 and eudragit RSPO and three dependent variables, particle size, % entrapment efficiency (EE) and % drug release at 24 h. The optimized formulation had adequat% EE, % drug release at 24 h and particle size. The particle size for optimized nanogel was 190.3 nm with % EE of 83.51% whereas % drug release at 24 h was found 90.13%. The optimized DCN nanogel was analyzed by differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (DTIR) and transmission electron microscopy (TEM) studies. The drug release kinetic study has shown that the gel followed Higuchi's model and the diffusion was anomalous in nature. The nanogel was characterized for physical examination, viscosity, homogeneity and stability parameters and the results obtained were found upto the mark. The ex-vivo permeation study data was in correlation with results of in-vitro study. In-vivo anti-arthritic study proved the efficacy of developed formulation for arthritis in Freund's Adjuvant Arthritic model. This research work has proved the significant potential of innovated product for arthritis by topical route, as it overcomes the drawbacks of oral route, highly efficient, sustained and targeted the release of drug without any accumulation and toxicity.

An exhaustive comprehension of the role of herbal medicines in Pre- and Post-COVID manifestations.

ETHNOPHARMACOLOGICAL RELEVANCE: The coronavirus disease (COVID-19) has relentlessly spread all over the world even after the advent of vaccines. It demands management, treatment, and prevention as well with utmost safety and effectiveness. It is well researched that herbal medicines or natural products have shown promising outcomes to strengthen immunity with antiviral potential against SARS-COV-2. AIM OF THE REVIEW: Our objective is to provide a comprehensive insight into the preventive and therapeutic effects of herbal medicines and products (Ayurvedic) for pre-and post-COVID manifestations. MATERIAL AND METHOD: The database used in the text is collected and compiled from Scopus, PubMed, Nature, Elsevier, Web of Science, bioRxiv, medRxiv, American Chemical Society, and clinicaltrials.gov up to January 2022. Articles from non-academic sources such as websites and news were also retrieved. Exploration of the studies was executed to recognize supplementary publications of research studies and systematic reviews. The keywords, such as "SARS-COV-2, coronavirus, COVID-19, herbal drugs, immunity, herbal immunomodulators, infection, herbal antiviral drugs, and WHO recommendation" were thoroughly searched. Chemical structures were drawn using the software Chemdraw Professional 15.0.0.160 (PerkinElmer Informatics, Inc.). RESULT: A plethora of literature supports that the use of herbal regimens not only strengthen immunity but can also treat SARS-COV-2 infection with minimal side effects. This review summarizes the mechanistic insights into herbal therapy engaging interferons and antibodies to boost the response against SARS-COV-2 infection, several clinical trials, and in silico studies (computational approaches) on selected natural products including, Ashwagandha, Guduchi, Yashtimadhu, Tulsi, etc. as preventive and therapeutic measures against COVID. We have also emphasized the exploitation of herbal medicine-based pharmaceutical products along with perspectives for unseen upcoming alike diseases. CONCLUSION: According to the current state of art and cutting-edge research on herbal medicines have showed a significant promise as modern COVID tools. Since vaccination cannot be purported as a long-term cure for viral infections, herbal/natural medicines can only be considered a viable alternative to current remedies, as conceived from our collected data to unroot recurring viral infections.

Tyrosine kinase inhibitors as next generation oncological therapeutics: Current strategies, limitations and future perspectives.

Protein kinases, a class of enzymes that govern various biological phenomena at a cellular level, are responsible for signal transduction in cells that regulate cellular proliferation, differentiation, and growth. Protein kinase enzyme mutation results in abnormal cell division leading to a pathological condition like cancer. Tyrosine kinase (TK) inhibitors, which helps as a potential drug candidate for the treatment of cancer, are continuously being developed. Majority of these drug candidates are being administered as conventional oral dosage form, which provides limited safety and efficacy due to non-specific delivery and uncontrolled biodistribution resulting into the adverse effects. A controlled drug delivery approach for the delivery of TK inhibitors may be a potential strategy with significant safety and efficacy profile. Novel drug delivery strategies provide target-specific drug delivery, improved pharmacokinetic behaviour, and sustained release leading to lower doses and dosing frequency with significantly reduced side effects. Along with basic aspects of tyrosine kinase, this review discusses various aspects related to the application of tyrosine kinase inhibitors in clinical oncological setting. Furthermore, the limitations/challenges and formulation advancements related to this class of candidates particularly for cancer management have been reviewed. It is expected that innovations in drug delivery approaches for TK inhibitors using novel techniques will surely provide a new insights for improved cancer treatment and patients' life quality.

Development of Nanomedicines and Nano-Similars: Recent Advances in Regulatory Landscape.

BACKGROUND: Nanopharmaceuticals serve as emerging forms of modern medicines, which include nanomedicines, nanosimilars, nanotheranostics, nanodevices, and many more. In the last two decades, a large number of nano-based products have reached the market and are being used clinically. OBJECTIVES: Unlike conventional pharmaceutical products, nanopharmaceuticals behave differently both in vitro and in vivo, and therefore, the development of their generic versions needs special attention to replicate the similar drug release pattern leading to an identical therapeutic outcome. Further, drug-device combinations and 3D products are the latest advancements in precision medicine delivery and development. METHODS: The regulatory guidelines for these products are being framed at many stages by various regulatory agencies like USFDA/EMA and still are in infancy at the moment if we look at wider perspectives and applications of nanomedicine. RESULTS: For a formulation scientist, it is much needed that well-explained and directive guidelines should be made available before leading to the development of the generic versions of these nano-cargos. CONCLUSION: Here, in this review, we have summarized the silent features of the regulatory perspectives related to nanotechnology based next generation therapeutics and diagnostics.

Nanotheranostics for Cancer Therapy and Detection: State of the Art.

Nanotheranostics, an approach of combining both diagnosis and therapy, is one of the latest advances in cancer therapy particularly. Nanocarriers designed and derived from inorganic materials such as like gold nanoparticles, silica nanoparticles, magnetic nanoparticles and carbon nanotubes have been explored for tremendous applications in this area. Similarly, nanoparticles composed of some organic material alone or in combination with inorganic nano-cargos have been developed pre-clinically and possess excellent features desired. Photothermal therapy, MRI, simultaneous imaging and delivery, and combination chemotherapy with a diagnosis are a few of the known methods exploring cancer therapy and detection at organ/tissue/molecular/sub-cellular level. This review comprises an overview of the recent reports meant for nano theranostics purposes. Targeted cancer nanotheranostics have been included for understating tumor micro-environment or cell-specific targeting approach employed. A brief account of various strategies is also included for the readers highlighting the mechanism of cancer therapy.

Dual cancer targeting using estrogen functionalized chitosan nanoparticles loaded with doxorubicin-estrone conjugate: A quality by design approach.

In this study, estrone was used as targeting functionality in chitosan nanoparticles (DoxEs-CSEsNPs) carrying doxorubicin-estrone conjugate for dual targeted intracellular delivery to breast cancer cells. Estrone was conjugated with Dox and CS and characterized by FTIR and FT-NMR spectroscopy. Dox/DoxEs containing CSEsNPs were prepared with ionic gelation method and for the effect of formulation variables a 3-factor, 3-level Box-Behnken design (BBD) was explored, which predict the responses like particle size (Y1) and percent entrapment efficiency (%EE) (Y2) when CSEs: TPP ratio (X1), sonication time (X2) and stirring speed (X3) were selected as independent variables. The Dox-CSEsNPs and DoxEs-CSEsNPs were characterized for size, shape, PDI, surface charge and thermal analysis. The drug entrapment efficiency was 66.33 ± 2.82% and 62.25 ± 2.63% for Dox-CSEsNPs and DoxEs-CSEsNPs formulation respectively. The in vitro release, haemolytic toxicity, and fluorescent microscopy studies were also assessed. Anticancer activity on the MCF-7 cell line indicated the higher potency of DoxEs-CSEsNPs as compared to Dox-CSEsNPs, DoxEs, and Dox solution. The findings are decisive for selective targeting of antineoplastic agents to the ERs, which indicate that the DoxEs loaded CSEsNPs were able to significantly improve the efficacy of Dox.

Galactosylated TPGS Micelles for Docetaxel Targeting to Hepatic Carcinoma: Development, Characterization, and Biodistribution Study.

Hepatocellular carcinoma (HCC) is a foremost type of cancer problem in which asialoglycoprotein receptors are overexpressed. In this study, asialoglycoprotein receptor-targeted nanoformulation (galactose-conjugated TPGS micelles) loaded with docetaxel (DTX) was developed to achieve its site-specific delivery for HCC therapy. The pharmaceutical characteristics like shape morphology, average particle size and zeta potential, drug entrapment efficiency, and in vitro release kinetics of developed system were evaluated. DTX-loaded galactosylated TPGS (DTX-TPGS-Gal) micelles and TPGS micelles (DTX-TPGS) were having 58.76 ± 1.82% and 54.76 ± 1.42% entrapment of the DTX, respectively. In vitro drug release behavior from micelles was controlled release. Cytotoxicitiy (IC50) of DTX-TPGS-Gal formulation on HepG2 cell lines was significantly (p ≤ 0.01) lower (6.3 ± 0.86 µg/ml) than DTX-TPGS (9.06 ± 0.82 µg/ml) and plain DTX (16.06 ± 0.98 µg/ml) indicating higher efficacy of targeted formulation. Further, in vivo biodistribution studies in animal model showed maximum drug accumulation at target site, i.e., the liver in the case of DTX-TPGS-Gal as compared with non-targeted one. It is concluded from the findings that TPGS-Gal micelles can be utilized for targeted drug delivery of cytotoxic drugs towards HCC with minimized side effects. Graphical abstract.

Solid lipid nanoparticles: a review on recent perspectives and patents.

Introduction: Solid lipid nanoparticles (SLNs) are solid core lipid nanocarriers, which can hold both hydrophilic and hydrophobic drugs. They can be made up of biocompatible ingredients and therefore are one of the preferred choices for drug delivery. Surface modifications of SLNs may further provide unique features to them like mucoadhesiveness or targeting capability.Areas covered: In this review, the authors have covered areas from the basic introduction of SLNs to its applications in controlled drug delivery. More specifically, the authors have covered patents disclosed related to the SLNs for the period 2014-2019; however, a summary of patents of 2008-2013 is also included.Expert opinion: SLNs have been explored for development of compositions/formulations with improved therapeutics or cosmetic applications or for nutraceutical applications. Targeted SLNs compositions have been patented as evidenced from the literature; however, not such types of enough SLNs formulations have been claimed for the same.

Rheumatiod Arthritis: An Updated Overview of Latest Therapy and Drug Delivery.

Rheumatoid arthritis is a severe autoimmune disorder, related to joints. It is associated with serious cartilage destruction. This causes disability and reduces the excellence of life. Numerous treatments are existed to combat this disease, however, they are not very efficient and possess severe side effects, higher doses, and frequent administration. Therefore, newer therapies are developed to overcome all these limitations. These include different monoclonal antibodies, immunoglobulins, small molecules used for immunotherapy and transgenes for gene therapy. One of the main goals of these new generation therapeutics is to address the underlying distressing biological processes by specifically targeting the causative agents with fewer systemic side effects and greater patient console. It is very fortuitous that loads of progressive investigations are going on in this field and many of them have entered into the successful clinical trial. But till date, a limited molecule has got FDA clearance and entered the market for treating this devastating disease. This review highlights the overview of conventional therapy and advancements in newer therapeutics including immunotherapy and gene therapy for rheumatoid arthritis. Further, different novel techniques for the delivery of these therapeutics of active and passive targeting are also described.

Transdermal Drug Delivery: Opportunities and Challenges for Controlled Delivery of Therapeutic Agents Using Nanocarriers.

BACKGROUND: Transdermal drug delivery represents an extremely attractive and innovative route across the skin owing to the possibility for achieving systemic effect of drugs. The present scenario demands a special focus on developing safe medicine with minimized toxic adverse effects related to most of the pharmacologically active agents. Transdermal drug delivery would be a focal paradigm which provides patient convenience, first-pass hepatic metabolism avoidance, local targeting and reduction in toxic effect related to various categories of drugs like, analgesics, antiinflammatory, antibiotics, antiviral, anaesthetic, anticancer etc. Even this route has challenges due to highly organized structure of skin which acts as a main barrier to penetration of drug via the skin. METHOD: Several alternative possible strategies are available which overcome these barriers, including use of penetration enhancer, eletroporation, iontophoresis and various nanotechnologically developed nanocarrier systems. The latest one includes employing liposome, dendrimers, nanoparticles, ethosome, carbon nanotube and many more to avoid associated limitations of conventional formulations. Numerous transdermal products such as Estrasorb, Diractin, VivaGel®, Daytrana®, Aczone, Sileryst® are available in the market having a novel strategy to achieve higher penetration of drugs. This encourages formulation fraternity to develop structurally deformable and stable nanocarriers as an alternative approach for controlled and reliable drug delivery across the skin barrier. DISCUSSION: In this review, we will discuss nanocarriers mediated approaches that come-up with the solutions to the different challenges towards transdermal drug delivery, its clinical importance and latest insight to research in it. CONCLUSION: The reports presented in this review confirm the wide application of nanocarriers for transdermal delivery of drug/gene.

Hyaluronic acid modified pH-sensitive liposomes for targeted intracellular delivery of doxorubicin.

CONTEXT: Surface-modified pH-sensitive liposomal system may be useful for intracellular delivery of chemotherapeutics. OBJECTIVE: Achieving site-specific targeting with over-expressed hyaluronic acid (HA) receptors along with using pH sensitive liposome carrier for intracellular drug delivery was the aim of this study. MATERIALS AND METHODS: Stealth HA-targeted pH-sensitive liposomes (SL-pH-HA) were developed and evaluated to achieve effective intracellular delivery of doxorubicin (DOX) vis-a-vis enhanced antitumor activity. RESULTS: The in vitro release studies demonstrated that the release of DOX from SL-pH-HA was pH-dependent, i.e. faster at mildly acidic pH ∼5, compared to physiological pH ∼7.4. SLpH-HA was evaluated for their cytotoxicity potential on CD44 receptor expressing MCF-7 cells. The half maximal inhibitory concentration (IC50) of SL-pH-HA and SL-HA were about 1.9 and 2.5 µM, respectively, after 48 h of incubation. The quantitative uptake study revealed higher localization of targeted liposomes in the receptor positive cells, which was further confirmed by fluorescent microscopy. The antitumor efficacy of the DOX-loaded HA-targeted pH-sensitive liposomes was also verified in a tumor xenograft mouse model. DISCUSSION: DOX was efficiently delivered to the tumor site by active targeting via HA and CD44 receptor interaction. The major side-effect of conventional DOX formulation, i.e. cardiotoxicity was also estimated by measuring serum enzyme levels of LDH and CPK and found to be minimized with developed formulation. Overall, HA targeted pH-sensitive liposomes were significantly more potent than the non-targeted liposomes in cells expressing high levels of CD44. CONCLUSION: Results strongly implies the promise of such liposomal system as an intracellular drug delivery carrier developed for potential anticancer treatment.

Nanocarriers in Improved Heparin Delivery: Recent Updates.

Heparin, a well known drug for anticoagulant therapy and prophylaxis of deep vein thrombosis and coronary syndromes, is also involved in numerous pathological processes such as inflammation, immune cell migration, tumor cell metastasis, smooth muscle cell proliferation etc. Though heparin is a clinically used anticoagulant with minimal side effects and drug interactions, its clinical use is limited due to parenteral administration. Alternatively, noninvasive delivery approaches such as oral, nasal, pulmonary or transdermal route are being explored that may deal with problems associated with parenteral heparin without compromising therapeutic benefits. For the successful noninvasive delivery of such a large drug candidate, the biological and biochemical barriers must be overcome to achieve a clinically acceptable therapeutic advantage. Nanocarriers significantly improve the pharmacokinetics and clinical effectiveness of the loaded therapeutics by either protecting them from unfavorable bioenvironment or modifying their release at the target site. Novel carriers such as liposomes, nanoparticles, dendrimers etc. have been developed to improve the bioavailability of heparin through various routes of delivery. Overall, the present review provides complete insight to the research that has been carried out for heparin delivery through various routes.