Volume 6, Issue 1, February Issue - 2018, Pages:87-107
|Authors: Sonu Ambwani*, Roopali Tandon, Tanuj Kumar Ambwani, Yashpal S. Malik|
|Abstract: Herbal remedies have been extensively used since times immemorial throughout the world. These have wide acceptability due to their time-tested therapeutic values and minimal side effects in contrast to modern allopathic medicines. Commonly, the herbal medicines are available in the form of crude extracts prepared in different solvent systems which might not only need large dose administration but also could be less effective in the form of conventional formulations. Moreover, available phyto-formulations do not have the ability for specific tissue target delivery in case of different chronic diseases. Oral administration of these herbal formulations is subjected to adverse pH, enzymatic degradation and ultimately poor gut absorption and bioavailability. With the advancements in biotechnology, genomics, and combinatorial chemistry, new, more potent and specific drug delivery systems have been envisaged during the last few decades. Constraints associated with conventional phytopharmaceuticals have been improved by designing and using “Nano Delivery Systems” (NDS). The foremost aim of NDS is to provide sustained drug release, site-specific action, and improved patient’s compliance. Nano herbal medicines can be used to target them to the specific site in the body which improves their selectivity, solubility, delivery, safety, effectiveness and thus reduces the need for administration of frequent large doses. Nanocarriers loaded with herbal drugs can carry the optimal amount of the drug to their site of action avoiding different obstructions such as low pH in the stomach, metabolism by liver so that the drug can circulate into the blood for a longer period of time. Phytopharmaceuticals with NDS thus would be helpful in enhancing the efficacy of herbal drugs.|
|Full Text: |
From last decade there has been a wide acceptance and public interest in natural remedies both in developing and developed countries. As per World Health Organization (WHO) “herbal medicines as finished, labeled medicinal products that contain active ingredients, aerial or underground parts of the plant or other plant material or combinations”. According to WHO reports, 80% of the populations from developing countries exploit herbal medicines for their primary health care needs (Yadav et al., 2014). Herbal ‘renaissance’ is happening all over the world due to rising concern over the safety of modern allopathic medicines. Various modern medicines are causing side effects and not able to effectively treat many of the common health conditions with increased incidences of drug resistance. Even the genesis of modern medicine is from traditional therapeutic systems (Patwardhan et al., 2004). Plants and natural products have been used since long for curative/ healing purposes in different cultures like China, Egypt, Africa, America and India. Herbal medicine, also known as “herbalism” or “botanical medicine” is a medical system based on the use of plants or plant extracts that may be taken orally or applied to the skin (Griggs, 1982). In spite of criticisms regarding certain features of herbal medicine, many pharmacologists today, recognize the potential scientific rationale of biological effects produced by these phytomedicines (Sharma et al., 2011).
Though herbal medicines are considered as dependable and affordable therapeutics, however, some problems are associated with them viz. rapid release of the herbal drug, unknown toxicity, low solubility, poor bioavailability and oral absorption, etc. (Thillaivanan & Samraj, 2014). Besides the general notion that “the herbal drugs are safe”, many pharmaco-vigilance studies have suggested that these natural drugs have frequently unknown active ingredients and thus their standardization and quality control are not an easy task (Ekor, 2013; Mathur, 2016). Delivery of herbal medicines also requires an improved delivery system for their sustained release and targeted delivery for enhanced patient compliance (Goyal et al., 2011). NDS is a new concept of drug delivery that can be helpful in surmounting the shortcomings of the traditional drug delivery systems. NDS, when employed for herbal medicine, may be helpful in enhancing the efficacy and lowering their side effects (Ansari et al., 2012). In novel phytoformulations, various nano delivery vehicles, viz., liposomes, polymeric nanoparticles, nanoemulsion, nanospheres, solid lipid nanoparticles (SLNs), are used in which phytoconstituents can be incorporated and these nanosized herbal formulations not only help in sustained release of the drug but can also eliminate the inadequacies of conventional herbal formulations (Elmowafy et al., 2013; Priprem et al., 2015). Present communication deliberates upon various nano delivery systems that could be exploited to eliminate shortcomings of conventional herbal formulations and thus can be helpful in improvement of therapeutic efficacy of phytomedicines.
2 Advantages of herbal drugs
Herbal medicine based therapeutic system is the ancient form of health care system known to human civilization. Phyto-formulations may contribute immensely to the health of an individual (Mathur, 2016). An exponential increase in human population, insufficient availability of costly allopathic drugs, associated side effects and problems like multidrug resistance amongst infectious pathogens have led to the development of alternative plant-based natural medicines for a broad range of diseases (Greenwell & Rahman, 2015). Phytomedicine or phytopharmaceutical, is a complex mixture derived from plant sources that is used as a medicine or drug. Approximately 50% of the functional drugs are prepared from natural resources (Kingston, 2011).
Herbal formulations are cost effective and made up from natural ingredients that are readily metabolized in the body. Herbal preparations have been recognized for their potential curative and low side effects in comparison to other drugs (Mahima et al., 2012). Herbal drugs are reputed for treating diverse disease conditions associated with various systems like endocrine, skeletal, digestive, physiological, nervous, reproductive, respiratory and immune systems. These biological properties of herbal drugs are attributed to the biological activities of various secondary metabolites like phenolics, terpenoids (sapogenin), alkaloids, steroids etc., present in them (Mathur, 2016). Herbal products can also be used to increase the bioavailability of the medicine (Kesarwani & Gupta, 2013).
3 Constraints of herbal drugs
Many herbal formulations are crude preparations with hydrophobic phytoconstituents and thus exhibit low solubility. Several other tribulations such as low solubility, bioavailability, and oral absorption lead to reduced efficacy which can limit the use of herbal medicines (Jantarat, 2013). Till recently, phytopharmaceuticals were not preferred for development of novel formulations due to their crude combinations that lack scientific rationalization and processing difficulties (Ekor, 2013; Thillaivanan & Samraj, 2014). Most of the herbal ingredients are extracted in different solvents that may exert toxic effects. When traditional herbal formulations are administered, only a low amount of dose reaches to the site and rest of the drugs get wasted as it is distributed throughout the body depending on physicochemical and biochemical properties resulting in low therapeutic value. Another constraint of oral herbal formulations is that many ingredients of the herbal drugs may get deteriorated in the acidic pH of the stomach while some others may be metabolized in the liver so that inadequate amount of the phytopharmaceuticals may reach the blood (Yadav et al., 2011; Ansari et al., 2012). There would be either slow or no therapeutic effect if drug is not administered in the optimum quantity/ dose (minimum effective dose level). Some of the phytoconstituents derived from the natural origin have poor solubility and low bioavailability resulting in a narrow therapeutic index, thus scientists are working on drug targeting and controlled release of phytoconstituents to provide better therapeutic effect and increased patient compliance (Park, 2014).
The route of administration of the drug has a considerable impact on its effectiveness. A drug molecule needs to be given in an optimal concentration (dose) to achieve its therapeutic potential. If it is given in a smaller amount than optimal concentration, no therapeutic benefit is derived and at higher concentration, it could exhibit toxic effects (Charman et al., 1999). Due to the above-mentioned constraints and poor efficacy of the treatment of relentless diseases, multidisciplinary approaches are envisaged for tissue-specific delivery of herbal therapeutics to enhance their pharmacokinetics, pharmacodynamics, bio-recognition, and efficacy. These novel delivery methods are based on interdisciplinary inputs of polymer chemistry, pharmacology, nanotechnology, bioconjugate chemistry, etc (Charman et al., 1999).
4 Nano Delivery Systems for herbal drugs
From past two decades, nanotechnology is exploited for efficacious drug delivery and tissue-specific targeting of drug (Kumar et al., 2015). Improved drug delivery techniques help in minimizing toxic effects and achieving enhanced effectiveness which is beneficial for the patients. Important attributes pertaining to herbal remedies could be improved component solubility, enhanced bioavailability, increased absorbency, reduced herbal doses, achieving steady-state therapeutic levels of drugs and overall better compliance (Ansari et al., 2012). Some of the strategies of drug delivery are employed to cross physical barriers, viz. blood-brain barrier (BBB) or on finding alternative suitable routes for drug delivery other than the oral delivery where drug constituents can be degraded (Kumar et al., 2015). At present “Novel Drug Delivery Systems” (NDDS) are exploited mainly for allopathic medicines. However, recent emphasis has been given to employing NDDS for safe, effective and time-tested ‘ayurvedic’ herbal drug formulation that could prove to be an attractive choice in the present scenario.
Delivery of pharmaceutical molecules is a process of administering it to the patient through suitable route to achieve a specific therapeutic effect. Common routes of drug delivery are per-oral (through the mouth), topical (skin), transmucosal (nasal, buccal, sublingual, vaginal, ocular and rectal) and inhalation routes. Modern phytopharmaceutical investigations can be exploited for development of NDDS based herbal drugs (Bhokare et al., 2016). NDDS includes various strategies for transporting a pharmaceutical molecule in the body to safely attain its desired curative effects which may either require its specific targeting or it might require systemic pharmacokinetics. In nutshell, NDDS are advance delivery approaches to enhance drug effectiveness by targeting the drug to the desired site, by controlling drug release to provide sustained curative effect and offer better safety (Nagavarma et al., 2012). NDDS includes carrier based drug delivery system (liposomes, niosomes, microspheres, resealed erythrocytes as drug carriers), trans-dermal Delivery Systems (sonophoresis), mucoadhesive delivery systems, supramolecular delivery systems and variable release delivery systems (osmotic pump, nanoencapsulation), etc. Due to the presence of diverse ingredients development of NDDS for herbal formulations is a challenging task (Nagavarma et al., 2012).
Nano herbal formulations can be employed for site-specific targeting of herbal medicines to enhance their selectivity, solubility, delivery, safety, and effectiveness. The nanosized drug increases their surface area thereby allowing quicker distribution in the blood and reduced toxicity while maintaining the therapeutic effects. The enhanced permeation and retention of nanoparticles (NPs) can also help to cross BBB (Kumar et al., 2015; Ganesan et al., 2017). Phyto-pharmaceuticals require a methodical strategy for efficient and sustained delivery to enhance patient acceptability and to prevent frequent drug administration. “Nano Delivery Systems” for herbal formulations can be employed for this purpose and combat limitations of herbal drugs. NDS help in enhancing therapeutic value and bioavailability and also decreasing frequent administration of herbal drugs (Govindarajan et al., 2017). Therefore, amalgamation of NDS in the traditional remedies is of vital importance for treatment of many chronic ailments like asthma, cancer, etc. (Aqil et al., 2013; Bonifácio et al., 2014; Sharma & Singh, 2014; Gunasekaran et al., 2014; Mathur, 2016). Flavonoids have shown to exhibit poor stability, bioavailability, and bioefficacy if administered through oral route (Manach et al., 2005). Due to this constraint, various bioactivities attained in vitro conditions reveal either poor or no in vivo activities. Bilia et al. (2014b) reviewed the role of NDS like nanospheres, nanocapsules, micro- and nanoemulsions, micelles, solid lipid nanoparticles and nanostructured lipid capsules, for resolving shortcomings associated with the oral delivery of flavonoids. Flavonoids displayed improved stability and absorption when administered through NDS (Dube et al., 2010; Manjili et al., 2016). It is further reported that nano-based flavonoids possess enhanced surface area, better stability and bioavailability due to receptor-mediated phagocytosis and endocytosis by specific cells (Tan et al., 2012). NDS also mediate controlled discharge of encapsulated flavonoids. Bilia et al. (2014b) concluded in their review that nanocarriers made of approved molecules referred to as “Generally Recognized as Safe” (GRAS) may be used for development of efficacious preparations of herbal functional foods, dietary supplements, and therapeutics. Different types of nanosized herbal formulations can be prepared to achieve the enhanced therapeutic potential of
Aggarwal D, Nautiyal U (2016) Ethosomes: A review. International journal of pharmaceutical and medical research 4 : 354-363.
Aisha AFA, Amin MSAM, Zhari I (2014) Preparation and characterization of nano liposomes of Orthosiphon stamineus ethanolic extract in soybean phospholipids. BMC Biotechnology 14: 23-34.
Ambwani S, Tandon R, Gupta A, Ambwani TK, Chauhan RS (2015) Nanoparticles: Utility, immuno-toxicology and ethical issues. Journal of Immunology and Immunopathology 17: 68-78.
Ambwani S, Kakade DP, Kandpal D, Arora S, Ambwani TK (2016) Cytotoxic effects of gold nanoparticles exposure employing in vitro animal cell culture system as part of nanobiosafety. AIP Conference Proceedings 1724, 020091 (2016); doi: http://dx.doi.org/10.1063/1.4945211.
Ansari SH, Islam F, Sameem M (2012) Influence of nanotechnology on herbal drugs: A Review. Journal of Advanced Pharmaceutical Technology & Research 3: 142-146.
Aqil F, Munagala R, Jeyabalan J, Vadhanam MV (2013) Bioavailability of phytochemicals and its enhancement by drug delivery systems. Cancer Letters 334 : 133–141.
Arora R, Kuhad A, Kaur IP, Chopra K (2015) Curcumin loaded solid lipid nanoparticles ameliorate adjuvantinduced arthritis in rats. European Journal of Pain 19 : 940- 952 .
Bagheri L, Madadlou A, Yarmand M, Mousavi ME (2013) Nanoencapsulation of date palm pit extract in whey protein particles generated via desolvation method. Food Research International 51: 866-871.
Bakry R, Vallant M, Najam-Ul-Haq M, Rainer M, Szabo Z, Huck CW, Bonn GK (2007) Medicinal Applications of Fullerenes. International Journal of Nanomedicine 2(4): 639–649.
Balakrishnan P, Shanmugam S, Lee WS, Lee WM, Kim JO, Oh DH (2009) Formulation and in vitro assessment of minoxidil niosomes for enhanced skin delivery. International Journal of Pharmaceutics 377:1-8.
Baldissera MD, Da Silva AS, Oliveira CB, Zimmermann CE, Vaucher RA, Santos RC, Rech VC, Tonin AA, Giongo JL, Mattos CB, Koester L, Santurio JM, Monteiro SG (2013) Trypanocidal activity of the essential oils in their conventional and nanoemulsion forms: in vitro tests. Experimental Parasitology 134:356–361. doi: 10.1016/j.exppara.2013.03.035.
Belletti D, Riva G, Luppi M, Tosi G, Forni F, Vandelli MA , Ruozi B, Pederzoli F (2017) Anticancer drug-loaded quantum dots engineered polymeric nanoparticles: Diagnosis/therapy combined approach. European Journal of Pharmaceutical Sciences 107: 230-239.
Bhattacharya R, Mukherjee P (2008) Biological properties of "naked" metal nanoparticles. Advanced Drug Delivery Reviews 60: 1289-1306.
Bhattacharya S (2009) Phytosomes: Emerging strategy in delivery of herbal drugs and nutraceuticals. Pharma Times 41: 9-12.
Bhokare SG, Dongaonkar CC, Lahane SV, Salunke PB, Sawale VS, Thombare MS (2016) Herbal novel drug delivery- a review. World Journal of Pharmacy and Pharmaceutical Sciences 5 : 593-611.
Bilia AR, Guccione C, Isacchi B, Righeschi C, Firenzuoli F, Bergonzi MC (2014a) Essential oils loaded in nanosystems: A developing strategy for a successful therapeutic approach. Evidence-Based Complementary and Alternative Medicine 2014:651593. doi: 10.1155/2014/651593.
Bilia AR, Isacchi B, Righeschi C, Guccione C, Bergonzi MC (2014b) Flavonoids Loaded in Nanocarriers: An Opportunity to Increase Oral Bioavailability and Bioefficacy. Food and Nutrition Sciences 5: 1212-1227.
Bisht S, Feldmann G, Soni S, Ravi R, Karikar C, Maitra A, Maitra A (2007) Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin"): A novel strategy for human cancer therapy. Journal of Nanobiotechnology 5: 3 DOI:10.1186/1477-3155-5-3.
Bonifácio BV, Silva PB, Ramos MA, Negri KM, Bauab TM, Chorilli M (2014) Nanotechnology-based drug delivery systems and herbal medicines: A review. International Journal of Nanomedicine 1-15.
Bonner JC (2007) Lung fibrotic responses to particle exposure. Toxicologic Pathology 35: 148–153.
Campos DA, Madureira AR, Sarmento B, Gomes AM, Pintado MM (2015) Stability of bioactive solid lipid nanoparticles loaded with herbal extracts when exposed to simulated gastrointestinal tract conditions. Food Research International 78: 131-140.
Cargnelutti LO, Denardi L, Boligon A (2016) A new biodegradable polymeric nanoparticle formulation containing Syzygiumcumini: Phytochemical profile, antioxidant and antifungal activity and in vivo toxicity. Industrial Crops and Products 83: 400-407.
Celia C, Cilurzo F, Trapasso F, Cosco D, Fresta M, Paolino D (2012) Ethosomes® and transfersomes containing linoleic acid: Physicochemical and technological features of topical drug delivery carriers for the potential treatment of melasma disorders. Biomedical Microdevices 14:119-130.
Cha C, Shin SR, Annabi N, Dokmeci MR, Khademhosseini A (2013) Carbon-based nanomaterials: Multi-functional Materials for Biomedical Engineering. ACS Nano 7:2891-2897.
Chan ES, Yim ZH, Phan SH, Mansa RF, Ravindra P (2010) Encapsulation of herbal aqueous extract through absorption with ca-alginate hydrogel beads. Food and Bioproducts Processing 88: 195-201.
Chandu V P, Arunachalam A, Jeganath S, Yamini K, Tharangini K, Chaitanya G (2012) Niosomes: A Novel Drug Delivery System. International Journal of Novel Trends in Pharmaceutical Sciences 2: 25-31.
Chao P, Deshmukh M, Kutscher HL, Gao D, Rajan SS, Hu P, Laskin DL, Stein S, Sinko PJ (2010) Pulmonary targeting microparticulate camptothecin delivery system: Anti-cancer evaluation in a rat orthotopic lung cancer model. Anti-Cancer Drugs 21: 10.1097/CAD.0b013e328332a322.
Charman WN, Chan HK, Finnin BC, Charman SA (1999) Drug delivery: A key factor in realising the full therapeutic potential of drugs. Drug Development Research 46:316–27.
Chaudhary H, Kohli K, Kumar V (2014) A novel nano-carrier transdermal gel against inflammation. International Journal of Pharmaceutics 465: 175-186.
Chen CYC, Wu CH (2008) Magnolol encapsulated by liposome in inhibiting smooth muscle cell proliferation. Journal of the Chinese Chemical Society 55: 517- 521.
Chen H, Chang X, Du D, Liu W, Liu J, Weng T, Yang Y, Xu H , Yang X (2006) Podophyllotoxin-loaded solid lipid nanoparticles for epidermal targeting. Journal of Controlled Release 110: 296-306.
Chen J-G, Jiang Y, Yang Zb (2012) Preparation of triptolide ethosomes. African Journal of Pharmacy and Pharmacology 6: 1341-1347.
Chen JG, Wei L, Yu J (2013) Preparation of curcumin ethosomes. African Journal of Pharmacy and Pharmacology 7: 2246-2251.
Chen Y, Lin X, Park H, Greever R (2009) Study of artemisinin nanocapsules as anticancer drug delivery systems. Nanomedicine: Nanotechnology, Biology and Medicine 5: 316-322.
Conacher M, Alexander J, Brewer JM (2000) Niosomes as immunological adjuvants. In Uchegbu IF (Ed.) “Synthetic Surfactant Vesicles” International Publishers Distributors Ltd. Singapore, Pp. 185-205.
Conte R, Marturano V, Peluso G, Calarco A, Cerruti P (2017) Recent Advances in Nanoparticle-Mediated Delivery of Anti-Inflammatory Phytocompounds. International Journal of Molecular Sciences 18: 709; doi: 10.3390/ijms18040709.
Costa DFG, Franca JR, Ribeiro TG, Kaplan MAC, Faraco AAG, Castilho RO (2013) Development and characterization of polymeric nanoparticles as Barbatimão (Stryphnodendron obovatum) standardized fraction carrier. Advances in Bioscience and Biotechnology 4: 89-92. DOI: http://dx.doi.org/10.4236/abb.2013.41013.
Crielaard BJ, Wal VD, Le HT, Bode AT, Lammers T, Hennink WE, Schiffelers RM, Fens MH, Storm G (2012) Liposomes as carriers for colchicines derived produrgs: vascular disrupting nanomedicnes with tailorable drug release kinetics. European Journal of Pharmaceutical Sciences 45: 429-435.
Datta PK, Arora S, Ambwani S (2018) Cytotoxic effect of silver nanoparticles in cancerous HeLa cells due to enhanced oxidative stress. Research Journal of Biotechnology 13: 68-74.
Dave V, Pareek A, Paliwal S (2012) Ethosome: A novel approach of transdermal drug delivery system. International Journal of Pharma and Bio Sciences 1:439-452.
Dayan N, Touitou E (2000) Carriers for skin delivery of trihexyphenidyl HCl: Ethosomes vs liposomes. Biomaterials 21: 1879–1885.
Dhule SS, Penfornis P, Frazier T, Walker R, Feldman J, Tan G, He J, Alb A, John V, Pochampally R (2012) Curcumin-loaded γ-cyclodextrin liposomal nanoparticles as delivery vehicles for osteosarcoma. Nanomedicine: Nanotechnology, Biology and Medicine 8: 440-451.
Dilnawaz F, Singh A, Mohanty C, Sahoo SK (2010) Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer therapy. Biomaterials 31: 3694-3706.
Dornian D, Hussein MZ, Kura AU, Fakurazi S, Shaari AH, Ahmad Z (2012) Preparation of Fe?O? magnetic nanoparticles coated with gallic acid for drug delivery. International Journal of Nanomedicine 7: 5745-756.
Dua JS, Rana AC, Bhandari AK (2012) Liposomes: Method of preparation and application. International Journal of Pharmaceutical Sciences and Research 3:14-20.
Dube A, Nicolazzo JA, Larson I (2010) Chitosan Nanoparticles Enhance the Intestinal Absorption of the Green Tea Catechins (+)-Catechin and (−)-Epigallocatechin Gallate. European Journal of Pharmaceutical Sciences 41: 219- 225.
Dwivedi P, Khatik R, Khandelwal K, Taneja I, Raju KSR, Paliwal SK, Dwivedi AK, Mishra PR (2014) Pharmacokinetics study of arteether loaded solid lipid nanoparticles: An improved oral bioavailability in rats. International Journal of Pharmaceutics 466: 321-327.
Ebrahimnezhad Z, Zarghami N, Keyhani M, Amirsaadat S, Akbarzadeh A, Rahmati M, Taheri MZ, Nejati-Koshki K (2013) Inhibition of hTERT Gene Expression by Silibinin-Loaded PLGA-PEG-Fe3O4 in T47D Breast Cancer Cell Line. Bioimpacts 3: 67-74.
Edmundson M C, Capeness M, Horsfall L (2014) Exploring the potential of metallic nanoparticles within synthetic biology. New Biotechnology 31: 572-578.
Ekambaram P, Sathali AAH, Priyanka K (2012) Solid Lipid Nanoparticles: A Review. Scientific Reviews & Chemical Communications 2: 80-102.
Ekor M (2013) The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Frontiers in Pharmacology 4: 177-186.
Elmowafy M, Viitala T, Ibrahim HM, Abu-Elyazid SK, Samy A, Kassem A (2013) Silymarin loaded liposomes for hepatic targeting: In vitro evaluation and HepG2 drug uptake. European Journal of Pharmaceutical Sciences 50:161-171.
Esmaeili A, Niknam S (2013) Characterization of nanocapsules containing Elaeagnus angustifolia L. extract prepared using an emulsion–diffusion process. Flavour and Fragrance Journal 28: 309–315.
Esmaeili A, Ebrahimzadeh M (2015) Preparation of Polyamide Nanocapsules of Aloe vera L. Delivery with In Vivo Studies. American Association of Pharmaceutical Scientists 16: 242–249.
Fatima GX, Rahul Raj S, Reshma I, Sandeep T, Shanmuganathan S, Chamundeeswari D (2014) Herbal Ethosomes - A Novel Approach in Herbal Drug Technology. American Journal of Ethnomedicine 1: 226-230.
Gadkari PV, Balaraman M (2015) Extraction of catechins from decaffeinated green tea for development of nanoemulsion using palm oil and sunflower oil based lipid carrier systems. Journal of Food Engineering 147: 14-23
Galib, Barve M, Mashru M, Jagtap C, Patgiri BJ, Prajapati PK (2011) Therapeutic potentials of metals in ancient India: A review through Charaka Samhita. Journal of Ayurveda and Integrative Medicine 2 : 55–63.
Gandhi A, Dutta A, Pal A, Bakshi P (2012) Recent trends of phytosomes for delivering herbal extract with improved bioavailability. Journal of Pharmacognosy and Phytochemistry 1: 6-14.
Ganesan P, Arulselvan P, Choi DK (2017) Phytobioactivecompound-based nanodelivery systems for the treatment of type 2 diabetes mellitus – current status. International Journal of Nanomedicine 12: 1097–1111.
Geetha R, Ashokkumar T, Tamilselvan S, Govindaraju K, Sadiq M (2013) Green synthesis of gold nanoparticles and their anticancer activity. Cancer Nanotechnology 4: 91-98.
Gibis M, Zeeb B, Weiss J (2014) Formation, characterization, and stability of encapsulated hibiscus extract in multilayered liposomes. Food Hydrocolloids 38: 28-39.
Gomes A, Ghosh S, Sengupta J, Datta P, Gomes A (2014) Herbonanoceuticals: A New Step towards Herbal Therapeutics. Medicinal and Aromatic Plants 3: 162. doi:10.4172/2167-0412.1000162.
González-Rodríguez ML, Rabasco AM (2011) Charged liposomes as carriers to enhance the permeation through the skin. Expert Opinion on Drug Delivery 8 : 857-871.
Govindarajan Karthivashan, Palanivel Ganesan, Shin-Young Park, Joon-Soo Kim, Dong-Kug Choi (2018) Therapeutic strategies and nano-drug delivery applications in management of ageing Alzheimer’s disease. Drug Delivery, 25:1, 307-320, DOI: 10.1080/10717544.2018.1428243.
Goyal A, Kumar S, Nagpal M, Singh I, Arora S (2011) Potential of novel drug delivery systems for herbal drugs. Indian Journal of Pharmaceutical Education and Research 45: 225-35.
Greenwell M, Rahman PKSM (2015) Medicinal Plants: Their Use in Anticancer Treatment. International Journal of Pharmaceutical Sciences and Research 6 : 4103–4112.
Griggs B (1982) Green Pharmacy: A History of Herbal Medicine. Viking Press, New York.
Gunasekaran T, Haile T, Nigusse T, Dhanaraju MD (2014). Nanotechnology: an effective tool for enhancing bioavailability and bioactivity of phytomedicine. Asian Pacific Journal of Tropical Biomedicine 4 : S1–S7.
Guterres SS, Alves MP, Pohlmann AR (2007) Polymeric Nanoparticles, Nanospheres and Nanocapsules for Cutaneous Applications. Drug Target Insights 2: 147–157.
He X, Li Q, Liu X, Wu G, Zhai G (2015) Curcumin-Loaded Lipid Cubic Liquid Crystalline Nanoparticles: Preparation, Optimization, Physicochemical Properties and Oral Absorption. Journal of Nanoscience and Nanotechnology 15: 5559-5565.
Hosseini SF, Zandi M, Rezaei M, Farahmandghavi F (2013) Two-step method for encapsulation of oregano essential oil in chitosan nanoparticles: Preparation, characterization and in vitro release study. Carbohydrate polymers 95: 50-56.
Hourani R, Kakkar A (2010) Advances in the elegance of chemistry in designing dendrimers. Macromolecular rapid communications 31: 947-974.
Husch J, Bohnet J, Fricker G, Skarke C, Artaria C, Appendino G, Schubert-Zsilavecz M, Abdel-Tawab M (2013) Enhanced absorption of boswellic acids by a lecithin delivery form (phytosome®) of boswellia extract. Fitoterapia 84: 89-98.
Iram F, Iqbal MS, Athar MM, Saeed MZ, Yasmeen A (2014) Glucoxylan-mediated green synthesis of gold and silver nanoparticles and their phyto-toxicity study. Carbohydrate Polymers 104: 29-33.
Iravani S (2011) Green synthesis of metal nanoparticles using plants. Green Chemistry 13: 2638-2650
Jadhav N, Powar T, Shinde S, Nadaf S (2014) Herbal nanoparticles: A patent review. Asian journal of Pharmaceutics 8 : 1-12.
Jain K, Kesharwani P, Gupta U, Jain N (2010) Dendrimer toxicity: Let's meet the challenge. International Journal of Pharmaceutics 394: 122-142.
Jantarat C (2013) Bioavailability Enhancement Techniques of Herbal Medicine: A Case Example of Curcumin. International Journal of Pharmacy and Pharmaceutical Sciences 5: 493-500.
Jia D, Barwal I, Thakur S, Yadav SC (2015) Methodology to nanoencapsulate hepatoprotective components from Picrorhiza kurroa as food supplement. Food Bioscience 9: 28-35.
Jiang HL, Cui YL, Qi Y (2013) Microencapsulation of rutin in chitosan-coated alginate microspheres through internal gelation technique. Advanced Materials Research 716: 433-458.
Jourghanian P, Ghaffari S, Ardjmand M, Haghighat S, Mohammadnejad M (2016) Sustained release Curcumin loaded Solid Lipid Nanoparticles. Advanced Pharmaceutical Bulletin 6 : 17-21.
Juzenas P, Chen W, Sun YP, Coelho MAN, Generalov R, Generalova N, Christensen IL (2008) Quantum dots and nanoparticles for photodynamic and radiation therapies of cancer. Advanced Drug Delivery Reviews 60: 1600-1614.
Kalele S, Gosavi S W, Urban J, Kulkarni S K (2006) Nanoshell particles: synthesis, properties and applications. Current Science 91:1038-1105.
Kalita B, Das MK, Sharma AK (2013) Novel phytosome formulations in making herbal extracts more effective. Research Journal of Pharmacy and Technology 6: 1295-1301.
Kaminskas LM, Boyd BJ, Porter CJ (2011) Dendrimer pharmacokinetics: The effect of size, structure and surface characteristics on ADME properties. Nanomedicine 6: 1063-1084.
Kannan S, Dai H, Navath RS, Balakrishnan B, Jyoti A, Janisse J, Romero R, Kannan RM (2012) Dendrimer-based postnatal therapy for neuroinflammation and cerebral palsy in a rabbit model. Science Translational Medicine 4: 130-146.
Kareparamban JA, Nikam PH, Jadhav AP, Kadam VJ (2012) Phytosome: A novel revolution in herbal drugs. International Journal of Research in Pharmacy and Chemistry 2: 299-310.
Karimi N, Ghanbarzadeh M, Hamishehkar H, Pezeshki A, Mostafayi H , Gholian MM (2015) Phytosome as novel delivery system for nutraceutical materials. International Journal of Current Microbiology and Applied Sciences 4: 152-159.
Kesarwani K, Gupta R (2013) Bioavailability enhancers of herbal origin: An overview. Asian Pacific Journal Of Tropical Biomedicine 3: 253-266.
Khan A, Shukla Y, Kalra N, Alam M, Ahmad MG, Hakim SR, Owais M (2007) Potential of diallyl sulfide bearing pH-sensitive liposomes in chemoprevention against DMBA-induced skin papilloma. Molecular Medicine 13: 443-451.
Kingston DGI (2011) Modern natural products drug discovery and its relevance to biodiversity conservation. Journal of Natural Products 74:496–511.
Krausz AE, Adler BL, Cabral V, Navati M, Doerner J, Charafeddine RA (2015) Curcumin-encapsulated nanoparticles as innovative antimicrobial and wound healing agent. Nanomedicine 11:195-206 doi: 10.1016/j.nano.2014.09.004.
Krug HF, Wick P (2011) Nanotoxicology: an interdisciplinary challenge. Angewandte Chemie International Edition 50: 1260-1278.
Kumar AB, Habbu P, Thimmasetty L, Hullatti P, Kumar RS (2017) Phytosomes as Novel Drug Delivery System for Herbal Medicine – Systematic Reviews in Pharmacy 8: 5-7.
Kumar K, Rai AK (2012) Evaluation of ant-inflammatory and anti-arthritic activities of floating microsphere of herbal drug. International Research Journal of Pharmacy 3 : 186-193.
Kumar KP, Radhika P, Sivakumar T (2010) Ethosomes-a priority in transdermal drug delivery. International Journal of Advances in Pharmaceutical Sciences 1: 111-121.
Kumar P, Kulkarni PK, Srivastava AA (2015) Pharmaceutical application of nanoparticles in drug delivery system. Journal of Chemical and Pharmaceutical Research 7: 703-712.
Kumbhani J, Tank C, Upadhyay J, Darshit R, Nirali T, Hetal S (2016) Nanoparticle: A Promising carrier for Novel Drug Delivery. International Journal of Pharma Research & Review 5 : 27-40.