Pharmaceutical Nanotechnology - Volume 5, Issue 3, 2017

Background: C60-fullerenes (CFs) constitute a carbon-allotropic family with cage-like fused-ring structure, comprising of 20 hexagons and 12 pentagons. Since discovery in 1985, CFs attracted the scientists from various strata for unique properties like tensile strength, nanometeric size, symmetric nature, thermal and photo conductivity, chemical tailoring opportunities and drug loading capabilities. Surprisingly, CFs are also established to possess antiviral, neuroprotective, antiinflammatory, MRI contrast and antioxidant properties. Though extensively explored for chemical modifications and therapeutic benefits, CFs and derivatives also offer immense promises in drug delivery, especially to the cancerous cells. Objective: The present review is an attempt to highlight the promises of CFs in drug delivery, esp. of anticancer agents. The review also analyzes the safety concerns of CF-based drug delivery and attempts to discuss the promises and challenges in the light of preclinical and clinical data. Methods: The raw material (research/review articles) for the manuscript was collected from Pubmed, Google scholar and Scopus and the keywords used were fullerenes, nanotechnology, nanomedicine, functionalization, safety, drug delivery and biomedical applications. Conclusion: The drug release rate controlling behavior, higher drug loading, immuno-neutrality, substantial biocompatibility, capability to bypass mononuclear phagocytic system, long circulating nature and tissue extraction by virtue of enhanced permeability and retention effect are the major promises of these nanocarriers. On the other hand, the concerns like elimination from the biological system, anticipated tissue toxicity, stability of the final product, sterility issues and commercial viability pose challenges in proper utilization of CFs as ideal drug delivery carriers. However, a few commercial products based on CFs with human safety evidences provide a ray of hope.

Background: Nanomedicine is a branch which deals with medicinal products, devices, nonbiological complex drugs and antibody-nanoparticle conjugates and general health products that are manufactured using nanotechnology. Objective: Nano-medicine provides the same efficacies as traditional medicines owing to their improved solubility and bioavailability with reduced dosages. However, there are currently safety concerns due to the difficulties related to nanomaterial characterization; this might be the reason for unawareness of such medicines among the patients. The absence of clear regulatory guidelines further complicates matters, as it makes the path to registering them with regulatory bodies difficult. However, some products have overcome these obstacles and have been registered. While there are many international initiatives to harmonize the regulatory requirements and helps the industry to determine the most important characteristics that influence in vivo product performance. Conclusion: This review focuses on the various types of nanopharmaceuticals, and developments process with strategies tailored to upcoming regulations may satisfy the patients' needs.

Background: Nifedipine is a potential therapeutic agent for the treatment of cardiovascular disturbances, although it suffers from short half-life (t1/2, 2 hr). Objective: To address the problem, we first prepared nifedipine loaded sustained release microsponges and then formulated tablets for effective clinical application and patient compliance. Method: Preparations of microsponges were carried out using different compositions of nifedipine and polymer (1:1, 1:2 and 1:3 % molar ratio) using emulsion solvent diffusion technique. Results: The microsponges with molar ratio 1:3 (formulation code: MF-3) found optimized as revealed by analyzing surface morphology, better powder flow properties (angle of repose; 28.80 ± 0.9, Hausner ratio 1.15 ± 0.2, % compressibility 15.28 ± 0.5% and higher % drug content (80 ± 1.9 %). Different batches of tablets were then formulated incorporating MF-3 microsponges and different proportions (10-50 %) of microcrystalline cellulose and starch as additives. Among tablet formulations, batch composed of 48% of MF-3, 30% of MCC, 20 % of starch and 2 % of talc (TF-33), showed 92.73 ± 2.19 % drug release during 24 hr in vitro release study in comparison to other batches including commercial formulation which was found to be released completely in 20 hr. Further, stability analysis revealed good drug retention of loaded nifedipine as well as consistent in vitro release pattern over a period of 90 days at 40°C and 75% RH. Conclusion: The microsponge tablet delivery system was found to be superior concerning the therapeutic advantage as well as manufacturing feasibility of nifedipine.

Background: The convoluted pathophysiology of brain disorders along with penetration issue of drugs to brain represents major hurdle that requires some novel therapies. The blood-brain barrier (BBB) denotes a rigid barrier for delivery of therapeutics in vivo; to overcome this barrier, intranasal delivery is an excellent strategy to deliver the drug directly to brain via olfactory and trigeminal nerve pathways that originate as olfactory neuro-epithelium in the nasal cavity and terminate in brain. Method: Kind of therapeutics like low molecular weight drugs can be delivered to the CNS via this route. In this review, we have outlined the anatomy and physiological aspect of nasal mucosa, certain hurdles, various strategies including importance of muco-adhesive polymers to increase the drug delivery and possible clinical prospects that partly contribute in intranasal drug delivery. Results: Exhaustive literature survey related to intranasal drug delivery system revealed the new strategy that circumvents the BBB, based on non-invasive concept for treating various CNS disorders. Numerous advantages like prompt effects, self-medication through wide-ranging devices, and the frequent as well protracted dosing are associated with this novel route. Conclusion: Recently few reports have proven that nasal to brain drug delivery system bypasses the BBB. This novel route is associated with targeting efficiency and less exposure of therapeutic substances to non-target site. Nevertheless, this route desires much more research into the safe transferring of therapeutics to the brain. Role of muco-adhesive polymer and surface modification with specific ligands are area of interest of researcher to explore more about this.

Background: Conventional nanofiber forming peptide amphiphiles comprise a beta sheet forming, short peptide sequence with an alkyl chain attached at one terminus. We report the selfassembly of a peptide amphiphile possessing a mid-chain located alkyl substituent (a T-shaped peptide amphiphile) into nanofiber networks. Method: Peptide synthesis was carried out using standard 9-fluorenylmethoxycarbonyl solid phase peptide synthesis protocols, followed by covalent attachment of the alkyl chains to yield target peptide amphiphiles. Self-assembly was then studied using electron microscopy and coarse-grained molecular dynamics simulations. Results: T-shaped peptide amphiphiles self-assembled into nanofibers just like linear peptide amphiphiles, but then unlike linear peptide amphiphiles, T-shaped peptide amphiphiles formed inter-fiber associations and ultimately nanofiber networks. Conclusion: Changing the position of the alkyl chain in a peptide amphiphile from the terminal end of the peptide to the middle part of the peptide, to form a T-shaped peptide amphiphile, does not disrupt the molecular interactions required for the self-assembly of the peptide amphiphiles into nanofibers.

Background: Along with the intensified use of metal nanoparticles, growing concern of their adverse outcome on human health has also expanded, indicating that this work is an integral part of nanobioscience study. Objective: The aim of this study was to evaluate varied effect of biosynthesized gold nanoparticles (AuNPs) on normal and cancerous mammalian cells. Methods: AuNP synthesized and characterized by different characterization methods, here are produced by specifically isolated Aspergillus species, which is hardly explored in precious scientific findings. These bio-synthesized AuNP are then tested by MTT assay and further confirmed by different fluorescent staining methods. Results: The AuNPs synthesized here are fairly monodispersed and uniform in shape as confirmed by the relatively tall and dominant UV spectroscopy peak at 540 nm and TEM images showing round shaped particles at a magnification of 20 and 50 nm size ranges. The crystalline powder formed peaks at 2 angles specific for AuNPs verifying their presence and FT-IR validates presence of side groups which help in stabilization of particulates. We have clearly proved that the less toxic nature of these AuNPs on mouse fibroblasts cells and comparatively elevated inhibiting effect on cancer cells at as low as 1 μg/mL concentration of AuNP. Condensation of nucleus and damage of cells seen in fluorescent images also substantiates the results. Conclusion: This conclusion is encouraging to the nanoscientists to study elaborately their system pathways which might be responsible for varied toxicity levels of these AuNPs in mammalian cells and pursue different methods in biomedical applications.

Background: Chitosan nanoparticle, a potential vehicle, is used as a hydrophilic carrier system since it can deliver drugs to specific sites and also control the drug release rate. Moreover, controlled release systems are designed to minimize systemic absorption and to achieve optimum delivery of the biologically active mesalamine to the distal small intestine and the colon. Objective: The current study investigated the development of new nanoparticulate drug delivery systems based on polyurethane-chitosan copolymers. The copolymer shows good biodegradablity and biocompatiblity properties and thus can be considered as a potential carrier for drug delivery systems. Method: In this work, Polyurethane was obtained from the condensation reaction between polypropylene glycol (PPG) as prepolymerpolyol, 1, 4-butanediol (BD) as diol, dimethylol propionic acid (DMPA) as chain extender and also isophoronediisocyanate (IPDI). The synthesized polyurethane was grafted onto the prepared chitosan through a covalent binding and preparation of nanoparticles was done further through a coprecipitation process. The particle size of the prepared samples was evaluated with dynamic light scattering (DLS) technique. Results: The obtained particle size of the samples was 80±0.05 nm. Characterization of the synthesized chitosan-polyurethane copolymer was performed by FT-IR spectroscopy, 13CNMR and 11HNMR spectroscopy. The morphology of the synthesized polyurethane-chitosan copolymers and the amount of the loaded drug were also examined using SEM images and UV-visible spectroscopy, respectively. Moreover, drug release behavior was examined in PBS (pH 7.4) at 37°C. It was concluded that the mesalamine release from polyurethane-chitosan was sustained and no initial burst release (burst effect) was observed and the percentage of mesalamine released from nanoparticles was 92.19±0.2% within 72 hrs. Conclusion: The results of the drug loaded nanoparticles showed that the drug loading process was performed successfully. As a result, polyurethane-chitosan copolymer can be a good candidate for drug delivery systems.