Rohan Lalani
Maharaja Sayajirao University of Baroda
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Featured researches published by Rohan Lalani.
Current Pharmaceutical Design | 2015
Sushilkumar Patil; Imran Vhora; Jitendra Amrutiya; Rohan Lalani; Ambikanandan Misra
The advent of recombinant DNA technology and computational designing has fueled the emergence of proteins and peptides as a new class of modern therapeutics such as vaccines, antigens, antibodies and hormones. Demand for such therapeutics has increased recently due to their distinct pharmacodynamic characteristics of specificity of action and high potency. However, their potential clinical applications are often hindered by involvement of factors which impact their therapeutic potential negatively. Large size, low permeability, conformational fragility, immunogenicity, metabolic degradation and short half-life results in poor bioavailability and inferior efficacy. These challenges have encouraged researchers to devise strategies for effective delivery of proteins and peptides. Recent advances made in nanotechnology are being sought to overcome aforesaid problems and to offer advantages such as higher drug loading, improved stability, sustained release, amenability for non-parenteral administration and targeting through surface modifications. This review focuses on elaborating the role of nanotechnology based formulations and associated challenges in protein and peptide delivery, their clinical outlook and future perspective.
International Journal of Pharmaceutics | 2018
Priyanka Bhatt; Rohan Lalani; Imran Vhora; Sushilkumar Patil; Jitendra Amrutiya; Ambikanandan Misra; Rajashree Mashru
Combination strategy involving cyclodextrin (CD) complexation and liposomal system was investigated for Paclitaxel (PTX) to improve loading. Complexation was done using 2,6-di-O-methylbetacyclodextrin (DMβCD). Sterically stabilized double loaded PEGylated liposomes (DLPLs) containing PTX and PTX-DMβCD complex were prepared by thin film hydration. Physicochemical characterization of complex and prepared DLPLs was carried out. Cytotoxic potential, hemolytic potential and pharmacokinetics of DLPLs were tested in comparison to Taxol®. Aqueous solubility of PTX increased by almost 3 × 104 folds due to complexation with DMβCD as compared to pure drug solubility. Liposomal system was found to have 162.8 ± 4.1 nm size, zeta potential of -5.6 ± 0.14 mV and 2-fold increase in drug loading to 5.8 mol % for PTX due to double loading. DLPLs had low hemolytic potential and higher cytotoxicity on SKOV3 cells with improvement in IC50 value by 4.2 folds as compared to Taxol® at 48 h. The anti-angiogenic potential of DLPLs was confirmed by 1.33 folds lesser wound recovery in SKOV3 cells compared to Taxol®. In-vivo pharmacokinetic evaluation of DLPLs in rats substantiates improvement in circulation time, higher plasma concentration and decreased clearance rate compared to Taxol®. An efficacious system with improved loading and pharmacokinetics was formulated as potential alternative for currently marketed PTX formulation.
RSC Advances | 2016
Sushilkumar Patil; Priyanka Bhatt; Rohan Lalani; Jitendra Amrutiya; Imran Vhora; Atul Kolte; Ambikanandan Misra
Chitosan is among the few polymers with high biocompatibility and low toxicity. In the area of siRNA delivery, chitosan has been noted for its high buffer capacity in endosomal pH range. However, its applications are limited due to unfavorable physicochemical properties such as poor solubility, colloidal instability, unionized nature and weak binding with nucleic acids at physiologic pH which leads to premature release of nucleic acids, poor cell uptake and transfection. In order to overcome these limitations of chitosan, low molecular weight chitosan (LMWC) were prepared to improve its solubility and colloidal stability at physiologic pH. The obtained LMWC was conjugated with protamine to impart cationic charge and induce preferential binding with siRNA at physiologic pH. The polyplex were subjected to ionic cross-linking resulting in particle size of 143.7 nm and zeta potential of +12.8 mV. The polyplexes displayed enhanced resistance to displacement in heparin competition assay and to degradation in serum stability studies. Covalent conjugation also provided combined advantage of higher uptake due to cationic charge of protamine and endosomal escape capability of LMWC. The conjugate showed low cytotoxicity, high transfection efficiency and gene expression in vitro and were found safe in vivo.
Current Drug Metabolism | 2017
Rohan Lalani; Ambikanandan Misra; Jitendra Amrutiya; Hinal Patel; Priyanka Bhatt; Vivek Patel
BACKGROUND Protein and peptides in biological system form an important part of innate immune system and are being explored for potential use in various diseases as therapeutics. Importance of proteins and peptides as a new class of antimicrobial agents has boosted research in the field of biotechnology as potential alternative to antibiotic agents. OBJECTIVE Protein and peptides antimicrobial as a therapeutic class are structurally diverse and exhibit potent activity against microbes by various mechanisms. However, they present formidable challenge in formulation due to requirement of specific spatial configuration for their activity and stability. Thus, encapsulation of these therapeutics in various nano-systems may sustain activity along with improvement in stability. METHOD The article highlights the need for antimicrobial peptides in dermal infections along with discussion of mechanism of their action. It highlights challenges faced for dermal delivery and research carried out for their successful delivery using nano-systems. RESULTS It is widely realized that these novel classes of therapeutic agents have tremendous market potential to emerge as an alternative to conventional antibiotic agents for combating issue of multidrug resistant microbial species. Research in their delivery aspects by use of current advances made in delivery systems through use of nanoconstructs offers much needed area for exploration and achieving success. CONCLUSION As there is an urgent need for coming up with new therapeutic agents for encompassing the increased burden of microbial diseases in human population as well as their delivery challenges, research in field will give the much-needed strategic advantage against pathogenic organisms.
Therapeutic Delivery | 2018
Ankit Javia; Jitendra Amrutiya; Rohan Lalani; Vivek Patel; Priyanka Bhatt; Ambikanandan Misra
The management of wounds and burns is becoming difficult using conventional therapeutics available due to resistance development by microbes. Therefore, there is an utmost need to develop therapeutic alternatives to these agents. Antimicrobial peptides have emerged as a novel class of agents for the effective management of wounds and burns due to their potent nature along with minimal chances of resistance development against them. This article focuses on highlighting the importance of these antimicrobial peptides among the various therapeutic alternatives for burns and wounds. Further, effective delivery strategies for these agents that are being employed and investigated are reported along with an overview of the importance of these agents in the coming years.
Aaps Pharmscitech | 2018
Vivek Patel; Rohan Lalani; Denish Bardoliwala; Saikat Ghosh; Ambikanandan Misra
Partition coefficient (log P) is a key physicochemical characteristic of lipophilic drugs which plays a significant role in formulation development for oral administration. Lipid-based formulation strategies can increase lymphatic transport of these drugs and can enhance bioavailability many folds. The number of lipophilic drugs in pharmacopoeias and under discovery are continuously increasing and making the job of the formulation scientist difficult to develop suitable formulation of these drugs due to potent nature and water insolubility of these drugs. Recently, many natural and synthetic lipids are appearing in the market which are helpful in the development of lipid-based formulations of these types of drugs having enhanced solubility and bioavailability. One such reason for this enhanced bioavailability is the accessibility of the lymphatic transport as well as avoidance of first-pass effect. This review discusses the impact of lipophilicity in enhancing the intestinal lymphatic drug transport thereby reducing first-pass metabolism. The most appropriate strategy for developing a lipid-based formulation depending upon the degree of lipophilicity has been critically discussed and provides information on how to develop optimum formulation. Various formulation strategies are discussed in-depth by classifying lipid-based oral drug delivery systems with case studies of few marketed formulations with challenges and opportunities for the future of the formulations.
Recent Patents on Drug Delivery & Formulation | 2016
Rohan Lalani; Ambikanandan Misra; Jitendra Amrutiya; Hinal Patel; Priyanka Bhatt; Sushil K. Patil
BACKGROUND The development and progression of atherosclerosis is known to occur at a sluggish pace and the lesions remain concealed for a long duration before the factual situation of the complex atherosclerotic etiology affecting various organ gets apprehended. The root cause mainly involves an imbalance or malfunction of the cholesterol metabolizing pathway. The till date therapeutic alternatives include oral hypo-lipidemic agents along with advances made in biotechnology/tissue engineering and surgical procedures for management purpose. However, with the advent and upsurge of nanotech delivery systems, along with meticulous indulgence and identification of the causative genes in the etiology of disease have opened a new therapeutic area that has far reaching application potential for effective management of such chronic disease requiring lifelong therapy. METHODS Various genes that have implication in atherosclerosis were reviewed along with research in delivery vectors that have been employed for gene therapeutics and hurdles in successful delivery were elaborated. Relevant patents are discussed systematically to clearly support and highlight the developments made. RESULTS Patenting activity in the delivery of genes for atherosclerosis so far primarily covers use of viral vectors. With the identification of new targets, a list of candidate genes are available that can be potentially exploited for therapeutic purpose. Though the delivery of candidate genes using viral vectors has been well explored, the limitation of viral vectors have seized the much needed clinical success. Non-viral vectors can prove to be the key for conquering this limitations and offer a vast area for exploration for achieving an effective control and remission to the disease and increasing the assortment of patents as reviewed in this article. CONCLUSION In view of the many limitations in employing viral vectors for delivery, designing non-viral vectors for successful delivery of therapeutic gene in atherosclerosis should be realized and focused for effective management of the disease.
Cancer Research | 2016
Priyanka Bhatt; Rohan Lalani; Rajashree Mashru; Ambikanandan Misra
Purpose of the study was to prepare and characterize cyclodextrin-paclitaxel (CD-PTX) complex encapsulated immunoliposomes (ILs) conjugated with Fab’ fragment of anti-FSHR antibody and to determine their in vitro efficacy for cellular uptake, cytotoxicity, anti-metastatic activity and cell apoptosis on ovarian cancer (OC) cells. CD-PTX complex was formulated using Heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DMBCD) to improve aqueous solubility and liposomal loading of PTX. The complex was encapsulated in PEGylated liposomes (PLs) using reverse phase evaporation technique. ILs were prepared by covalent conjugation of Fab’ fragments of anti-FSHR antibody to functionalized PLs via thioether linkage which was confirmed by SDS-PAGE analysis. The ILs were characterized for size, zeta potential, entrapment, loading efficiency and in vitro drug release profile. ILs were also evaluated for uptake efficiency and in vitro cytotoxicity in FSHR-expressing Caov-3 OC cells. To establish anti-metastatic effect, the ILs, PLs and equal amounts of PTX solution were studied on Caov-3 cells by in vitro wound scratch assay. The effect of PTX solution, PLs and ILs on Caov-3 cell apoptosis and cell cycle was examined using FACS technique. Increased aqueous solubility of 11 mg/ml was achieved for PTX using DMBCD at molar ratio of 20 and the cytotoxic properties of CD-PTX complex was also retained similar to PTX as studied in Caov-3 cells. The PLs and ILs were found to be nanosized with optimum entrapment and improved loading efficiency of PTX. The in vitro release profiles exhibited controlled release of PTX from PLs (21.235±0.423%) and ILs (18.219±0.603%) after completion of 48 h. The IC50 values from MTT assay suggested that ILs was 3.7 and 8.1 times more cytotoxic than PLs and PTX solution respectively for Caov-3 cells after 24 h period. The ILs showed more anti-migration effect and less covered wound (39.66±5.2%) at a concentration of 3nM as compared with PTX solution (70.45±7.12%) and PLs (61.38±4.41%). After 24 h treatment no major distinction in% apoptosis was observed between PTX solution, PLs and ILs. However, after 48 h treatment, PLs and ILs respectively showed about 5.36% and 9.12% higher apoptosis when compared to PTX solution. In Caov-3 cells, after 48 h the ILs at 3nM concentration showed increased G2 phase cell arrest as compared to PLs which indicates the superiority of ILs. To conclude, ILs displayed improved intracellular uptake and enhanced cytotoxic as well as anti-metastatic effects compared to PTX solution and PLs in OC cells. The results clearly highlight the importance of FSHR as one of the prominent targets for OC therapy and also the potential of anti-FSHR Ab Fab’ conjugated nanocarriers to reduce the limitations associated with OC chemotherapy. Citation Format: Priyanka Bhatt, Rohan Lalani, Rajashree Mashru, Ambikanandan Misra. Anti-FSHR antibody Fab’ fragment conjugated immunoliposomes loaded with cyclodextrin-paclitaxel complex for improved in vitro efficacy on ovarian cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2065.
Cancer Research | 2016
Rohan Lalani; Priyanka Bhatt; Mohan Rathi; Ambikanandan Misra
Aim of the study was to prepare and characterize RGD grafted PEGylated liposomes of gemcitabine (PLGs) and to evaluate its cellular uptake, in vitro anti-proliferative activity and apoptotic effect in siRNA pretreated lung cancer cells. PLGs were prepared by thin film hydration method and optimized for particle size, zeta potential and entrapment efficiency. Functionalization of liposomes was done by coupling reaction between DSPE mPEG and cRGD peptide by maleimide based reaction. Similarly, RGD grafted RRM1 siRNA liposomes were also formulated and evaluated. MTT assay was done to determine IC50 values of RGD grafted PLGs in A549 and H1299 cancer cells which were pre-treated with RGD grafted RRM1 siRNA loaded liposomes at a concentration of 50 pM of siRNA for gene silencing. DNA content analysis was done by flow cytometry using rhodamine in A549. The mode of cell death at different time and concentration was determined by FITC-AnnexineV assay in A549 cells and confocal microscopy was performed to assess the potential of RGD grafting on cellular uptake. RGD conjugated and unconjugated PLGs were found Nano sized and had negative zeta potential with entrapment of 65%. H1299 cell line showed more amount of viable cells after 48 hr as compared to A549 cells in RGD conjugated PLGs. siRNA pre-treated PLGs exposed cells showed significantly less IC50 values as compared to cells without siRNA pretreatment and non-grafted liposomes. The results showed that the RGD conjugated liposomes at the concentration of 7nM showed 46% G1 phase arrest in siRNA pretreated cells as compared to 22% G1 phase arrest without prior siRNA treatment at 16hr. Two types of mode of cell death were found during the FITC-Annexine V assay. At 24 hr, the treatment with RGD grafted PLGs resulted in 17% & 4.4% necrotic & apoptotic cell death respectively. While at equivalent drug concentration, the PLGs and drug solution showed 5.3% & 32.2% and 4.2% & 29.6% necrotic & apoptotic cell death respectively. Furthermore, the apoptosis was found to be time and concentration dependent. Results substantiate the sensitization effect by pre-exposure of siRNA in liposomal forms at Pico molar concentration along-with phagocytosis as mechanism of uptake of RGD-grafted liposomes. To conclude, prior silencing of the resistance imparting gene can manifest the effect of therapy by conferring improved sensitivity in cancer cell lines. The effect can further be augmented by employing receptor targeting peptides such as RGD. Hence, Nano-constructs of chemotherapeutic drugs conjugated with RGD can effectively target lung cancer cells and pretreatment of RRM1 siRNA can probably reduce the limitation of drug resistance associated with lung cancer chemotherapy. Citation Format: Rohan A. Lalani, Priyanka Bhatt, Mohan Rathi, Ambikanandan Misra. Improved sensitivity and in vitro efficacy of RGD grafted PEGylated gemcitabine liposomes in RRM1 siRNA pretreated cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2063.
RSC Advances | 2018
Sushilkumar Patil; Rohan Lalani; Priyanka Bhatt; Imran Vhora; Vivek Patel; Hinal Patel; Ambikanandan Misra