Exploring Novel Drug Delivery Platforms: Enhancing Efficacy and Reducing Systemic Toxicity

Novel drug delivery systems is the new system Recent advances in the understanding of pharmacokinetic & pharmacodynamic behaviour of drug have offer a more rational approach  to the development of optimal drug delivery system. the novel drug delivery systems (NDDS) are carriers which maintain the drug concentration in therapeutic range for longer period of time There are several advantages of novel drug delivery systems over conventional drug delivery.

1. Optimum therapeutic- drug concentration in the blood or in tissue may be maintained over a prolonged period of time.

2. Pre- determined release rates of extended period of time may be achieved.

3. Duration for short half- life drug may be increased.

4. By targeting the site of action, side effects may be eliminated.

5. Frequent dosing and wastage of the drug may be reduced or excluded. 6. Better patient compliance may be ensured.

Novel drug delivery systems

• Sustained- or controlled- drug delivery systems provide drug action at a pre determined rate by providing a prolonged or constant (Zero-order) release respectively, at the therapeutically effective levels in the circulation.

• Localized drug delivery devices provide drug action through spatial or temporal control of drug release (usually rate- limiting) in the vicinity of the target.

• Rate- pre-programmed drug delivery systems provide drug action by manipulating the release of drug molecules by system design which control the molecular diffusion of drug molecules.

• Targeted drug delivery provides drug action by using carries either for passive or active targeting or one base or self programmed approach, usually anchored with suitable sensory devices, which recognize their receptor at the target.

Table 1.0 Classification of sustained or controlled release system based on their rate – controlled mechanism.

                                Type of System                                     Rate control Mechanism

       
           
       
Fig 1.0: Schematic depiction of various classes of controlled release system

Reservoir- Type drug delivery system

In the reservoir- type drug delivery systems, drug is encapsulated in the drug reservoir compartment whose drug – releasing surface is covered by a rate- controlling an embryonic polymer membrane. The drug in the reservoir compartments can be drug in liquid – or solid type dispersion of drug in a liquid or solid type dispersion medium. The polymeric membrane can be fabricated from a homogeneous or heterogeneous non – porous polymeric material or semi- permeable membrane. The release of drug from this type of delivery system occurs at a nearly constant rate (Q/ t).

Ocusert

A truly continuous, controlled- release and zero – order kinetic fashion was achieved using ocusert. First marketed by Alza Corporation, California, the pilocarpine ocusert improved the non complience problems, low intra -ocular drug bioavailability and potential systemic side effect of pilocarpine. The systems consist of a pilocaroine-aliginate core of (drug) sandwiched between two transparent rate – controlling ethylene- venyl acetate co- polymerbased thin membrane. When this is placed under the upper eyelid, The pilocaroine molecules after getting dissolved in the lachrymal fluid are released through the rate controlling membranes at a pre programmed rate.

A mixture of pilocarpine and alginic acid in the drug reservoir releases the drug for almost one week. A thin membrane of ethylene venyl acetate (EVA) co polymer encloses the reservoir above and below. A retraining ring of the same material impregnated with titanium dioxide encloses the drug reservoir circumferentially (fig.1.1).

       
           
       
Novel Carrier For Controlled & Targeted Drug Delivery

As the knowledge of the molecular biology and pathophysiology of diseases has expanded, more therapeutically precised and purpose specific drug are being developed. These newly developed drugs have high potency (low therapeutic window) and required their localization of the particular site of their action. Most drugs are administrated by conventional immediate release dosage forms. They distribute freely throughout the body & accumulate the non – specific organs in an undesirable manner and thus produce adverse side effects. To reduce these slides and increased their therapeutic benefits, they should be delivered to their respective site of action, and hence suitable carrier systems becomes mandatory requirement. Various novel carriers have been developed for the purpose. Among these colloidal carriers such as liposomes, nano- particles & supra molecular system, i.e. micelles have gained more attention in the field of controlled and targeted drug delivery. Recently new carriers such as inorganic particles, liquids crystal, aquasomes, carbon nano tubes, dendrimers etc. Are also investigated for the specialized purpose. In the following section, these carriers for the same purpose are brief.

Colloidal carrier

Liposomes

Liposomes were discovered in the early 1960s by Bingham and co-workers and subsequently became the most extensive- explored drug -delivery system. Initially, through they were used to study in vitro simulated – biomembrane behaviour, subsequently, they enraged as strong therapeutic tools most notably in drug delivery and drug targeting. Structurally, liposomes are phospholipid -based colloidal vesicular structures in which hydrophilic core is entirely enclosed by membranous lipid bilayer’s. They may be classified on the basis of method of preparation, structural perameters or special function.

Nanosomes

Non – ionic surfactants vesicles (niosomes) or NSVS) are now widely studied as an alter - native to liposomes. Non -ionic surfactants vesicles results from the self- assembly of hydrated surfactants monomers. Non – ionic surfactants of wide variety of structural types have been found to be useful alternatives to phospholipids. Through the terminology suggests that distinctions exist between niosomes and liposomes of which the former is having chemical differences in the monomers units, niosomes posses physical properties, which are similar to liposomes, which are formed from phospholipids. As the name indicated, generally non- ionic surfactants vesicles are prepared by the incorporation of components containing non- ionic surfactants. However, they may also prepared with various ionic amphiphiles such as dicetylphosphate, stearylamine, etc. In order to achieve a stablevasicular suspension. It is important to identify and know the basic structural units of NSVs. while an amphiphilic head groups. The vesicles forming non-ionic compounds are mainly alkyl ether lipids. These can be broadly divided into two classes based on nature of their hydrophilic head groups, i.e. Alkyl ethers in which the hydrophilic head group consists of repeat glycerol subunits, related isomers or larger sugar molecules, and those in which the hydrophilic head group consists of repeat ethylene oxide subunits. In addition, alkyl esters, amides and fatty acids, and amino acids compounds also from vesicles. The ultimate identity of any niosomal system and hence its properties are determined by the factors listed in Fig. 1.2. It is thus obvious that all these variables must be carefully controlled in the design of a niosomal drug -delivery system.                               

Microparticles

The” microcapsules “are defined as a spherical particles with size varying from 50 nm to 2nm, containing a core substance. Microspheres are, in real sense, spherical empty particles. However, the term microcapsules & microspheres are often used interchangeably. In addition some releted terms are used as well for example, “microbeads” & “beads” are used alternatively. Sphere and spherical particles are also used for particles of large size & rigid morphology. The dried microspheres from free flowing powders .they consist of proteins or synthetic polymers, which bio degradable & ideally have a size range less than 200 ?m. The solid bio degradable microspheres bearing a drug dispensed or dissolved throughout particles matrix have potential in controlled- release of drugs. These carriers received much attention not only prolonged- release formulations but also for the carrier potential in drug targeting particularly anti- cancer drugs the tumour.

Pre-requisites for ideal micro particulate carriers are follows.

•Longer duration of action

•control of drug release

•Increase of therapeutic efficiency

•Protection of drug

•Biocompatibility

•Relative stability

•water -solubility or Dispensability

•Bioresorbability

•Targetability

•Polyvalency

Microspheres can be prepared by using any of appropriately selected method including in situ polymerization, solvent evaporation, coacervation phase separation, spray drying and spray congealing, etc., but the choice of techniques depends on the nature of the polymer used, the drug, the intended use and duration of therapy. The choice of method is depend on the following Determinants.

1. The particles size requirements.

2. The drug or the protein should not be adversely affected by the process.

3. Reproducibility of the release profile and the method.

4. No stability Problem.

5. There should be no toxic product associated with the final product.

A number of different substances both biodegradable as well as non- biodegradable have been investigated for the preparation of microspheres. These materials include the polymer of natural synthetic origin and also modified natural substances. Synthetic polymers employed as carriers materials are methyl methacrylate, acrolein, lactide, Glycolide and their co-polymers, ethylene vinyl acetate copolymer, polyanhydrides etc.

The natural polymers used for the purpose include albumin gelatin, starch, collagen & carrageenan, etc.

Applications Of Novel Drug Delivery Systems

Sustained and controlled- drug delivery

Controlled release of drug or encapsulated bioactives could be achieved using NDDS. Desired release pattern will definitely improve the pharmacokinetics and hence pharmacodynamics of drug. The controlled delivery of antibiotics in the treathment of H. Pylori via NDDS is an effective process compared to conventional one. Similarly, slow and sustained release oF drug from implants avoids regular administration of drug hence ensures patients compliance. Numerous applications of NDDS is sustained and controlled delivery of drug are enumerated. Some of them have already been discussed in preceeding sections. Deport formulations of short -acting peptides have been successfully developed using microparticle technology. Such peptides include leuprorelin acetate and triptoreline, Both lutenizing harmone releasing hormone agonist. Leuprorelin polylactided acid co-glycolide microspheres may be used as a monthly and three monthly dosage forms in the treatment of advancement prostrate cancer, endometriosis and other hormone responsive conditions. These microspheres effectively halt the progression of prostate cancer or endometeriosis in patients and are currently marketed as prostap SR. Other peptides formulated as sustained release microparticles include the angiotensin receptors- antagonist, L -158809, for the treatment of hypertension, thyrotropin releasing hormone for central nervous system stimulation, salmon calcitonin for the treatment of hypercalcemia or postmenopausal oeteoporosis and the immunosuppressant drug cyclosporin A. There are no. Of products available in the market for clinical studies as listed in Table 1.1.

        Drug                                         Indication                         Company Name