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Paenteral drug delivery
The parenteral route can refer to any administration route allowing the avoidance of the gastrointestinal tract and therefore the first-pass effect of drugs. Nevertheless, common usage more closely associates the term parenteral as being synonymous with “injectable.” The main clinical role of parenteral therapy is to administer drugs that cannot be given by the oral route, either because of their poor absorption properties or propensity to degrade in the gastrointestinal tract. The major routes of parenteral administration are intravenous, intramuscular and subcutaneous. These three routes satisfy to a large extent the four principal reasons for administering parenteral: therapy (definitive or palliative), prevention, diagnosis, and temporarily altering tissue function(s) to facilitate other forms of therapy [22]. It is estimated that 40% of all drugs administered in hospitals are in the form of an intravenous injection, since this route allows a rapid drug effect. Additional parenteral routes can also be utilized under special circumstances such as intrathecal, subconjunctival, intraocular or intra-articular routes.
Transdermal drug delivery
Transdermal delivery represents an attractive approach used to deliver drugs across the skin for systemic distribution. It involves drug transport to viable epidermal and or dermal tissue of the skin through local application. A major fraction of drug is then transported into the systemic blood circulation.
Transdermal application is a non-invasive method convenient for a variety of clinical indications [23]. It presents many advantages over the conventional oral route such as the avoidance of the first pass metabolism and a better patient compliance [24]. Nevertheless, the protective barrier nature of the skin limits the absorption of most drugs. Variety of strategies can be adopted for the enhancement of drug absorptions such as the use of penetration enhancers or drug carrier (e.g., nanoparticules) which penetrates through the skin more easily [23].
Pulmonary drug delivery
Pulmonary route of drug delivery is gaining much importance in the present day research field as it enables to target the drug delivery directly to lung for local and systemic treatment [25]. For local applications, it allows a direct access for the treatment of respiratory diseases with a rapid onset of drug action, and consequently, reduced side effects can be achieved [26][27]. Furthermore, it provides an enormous surface area and a controlled environment for systemic absorption of medications.
However, pulmonary administration presents also some drawbacks. Indeed, since the lungs are a major port of entry to the body, several barriers are present to avoid the invasion of unwanted airborne particles and to control their sterility. As a consequence, they also limit the therapeutic effectiveness of inhaled medications. The drug efficacy may therefore be affected by the delivered dose but also by the location where it is deposited in the respiratory tract. Furthermore, because of the relatively short duration of drug action, multiple daily inhalation maneuvers, ranging up to 9 times a day, can be required [5].
Nasal drug delivery
The nasal route is generally used for local diseases treatment such as nasal allergy, congestion or infections [23]. Recent years have shown that the nasal route can also be exploited for the systemic delivery of drugs. In general, among the primary targets for intranasal administration are pharmacologically active compounds with poor stability in gastrointestinal fluids, poor intestinal absorption and/or extensive hepatic first-pass elimination such as polar drugs, peptides or proteins [28].
The main advantage of the nasal route arises from the particular anatomical, physiological and histological characteristics of the nasal cavity, which provides potential for rapid drug absorption and quick onset of action. In addition, intranasal absorption avoids the gastrointestinal and hepatic presystemic metabolism, enhancing drug bioavailability in comparison with that obtained after gastrointestinal absorption [29].
Nasal administration, nevertheless, presents some disadvantages that must be considered during therapy. In addition to physicochemical properties of drugs, a variety of physiological and pathological conditions related to nasal mucosa may also influence the extent of nasal drug absorption and therapy efficacy [30]. Furthermore, the low volume of nasal cavity restricts the amount of drug formulation administrated to about 100-150 µL [31]. If nasal delivery of high doses of poorly water-soluble drugs is necessary, particular problems may appear such as irritation of mucosa.
Nanoparticles based on solid lipids
Solid lipid particles are composed of lipids and stabilizers in most cases surfactants, co-surfactants and coating materials. The ability to incorporate drugs into solid lipid nanoparticles offers a new prototype in drug delivery that could be used for secondary and tertiary levels of drug targeting. Hence, solid lipid nanoparticles hold great promise for reaching the goal of controlled and site specific drug delivery.
Those formulation ingredients are safe and under the generally recognized as safe (GRAS) status issued by the FDA [69]. Solid lipid particulate systems such as solid lipid nanoparticles (SLN), lipid microparticles (LM), nanostructured lipid carriers (NLC), lipospheres and lipid drug conjugates (LDC) have been sought as alternative carriers for therapeutic peptides, proteins and antigens due to their properties [69].
SLNs are produced by replacing the liquid lipid (oil) of an oil/water emulsion by a solid lipid or a blend of solid lipids [12]. SLNs offer unique properties such as smaller size, larger surface area, interaction of phases at the interfaces; and these properties are attractive for their ability to improve performance of nutraceuticals, pharmaceuticals and other materials [70]. SLNs present several advantages such as good biocompatibility, low toxicity, physical stability and a good delivery of lipophilic drugs. Important peptides such as cyclosporine A, insulin, calcitonin and somatostatin have been incorporated into solid lipid particles and are currently under investigation. This is one of the most popular approaches to improve oral bioavailability of poorly water soluble drugs [71].
Microemulsions and nanoemulsions
Microemulsions (ME) and nanoemulsions (NE) are lipid based nanocarrier systems wherein the dispersed phase could be as small as 20 nm [72]. ME and NE are isotropic mixtures of oil/water stabilized by surfactants frequently in combination with co-surfactants [3,4,41]. They have shown good dissolution properties and thermodynamic stability. The stabilizers prevent particle agglomeration and/or drug leakage. Permeation of the drug formulations is enhanced which can be exploited in transdermal delivery [41]. The capacity of ME and NE to dissolve large quantities of low soluble drugs along with their biocompatibility and ability to protect the drugs from hydrolysis and enzymatic degradation makes them ideal drug delivery vectors [73]. The major advantages of NE as drug delivery carriers include increased drug loading, enhanced drug solubility and bioavailability, reduced patient variability, controlled drug release, and protection from enzymatic degradation [74].
ME and NE have found wide applications in bioavailability enhancement and delivery through various administration routes, namely oral [75], parenteral [76], nasal [77], transdermal [78] or also ocular [79].
Hydrophilic acrylic lenses
Hydrophilic acrylic materials (Figure I. 17, c) are composed of a mixture of hydroxyethylmethacrylate (poly-HEMA) and hydrophilic acrylic monomer [134]. These lenses are cut in the dehydrated state and then hydrated and stored in solution. The water content between IOLs varies widely and can be as high as 38% [133]. Hydrophilic acrylic lenses are soft, somewhat compressible, and have excellent biocompatibility because of their hydrophilic surface. The wetting contact angle with water is lower than 50°. Most IOLs are single piece and designed for capsular bag implantation with few exceptions. Hydrophilic acrylic material is the easiest to handle and can be implanted through a very small incision (2 mm).
Silicone lenses
Silicone was the first material available for foldable IOLs. It is composed of polymers with a dialkyl or diaryl siloxane functional groups, and the simplest is polydimethylsiloxane [116]. Silicone (Figure I. 17 d) is hydrophobic with a contact angle with water of 99°, higher than that of hydrophobic acrylic materials. The refractive index is usually between 1.41 and 1.46, and the optic diameter is ranges from 5.5–6.5 mm [133]. Current models are 3 pieces with PMMA, polyvinyl difluoride (PVDF) or polyamide haptics. Because of the low refractive index, the optics is rather thick, requiring incisions larger than 3.2 mm to implant higher power lenses. These IOLs are no longer used nowadays [126].
Collamer lenses
Collamer is the name of the material used exclusively by STAAR® surgical company. The name comes from the combination of ‘collagen’ and ‘polymer’. These IOLs (Figure I. 17, e) are composed of a hydrophilic porcine collagen (<0.1%)/hydroxyethyl methacrylate copolymer with an ultraviolet-absorbing chromophore [23]. IOLs made from collamer are highly biocompatible, and easy to implant because of the softness of the material [135]. Indeed, water content is very high, at about 40%, which makes this material very soft [136].
Several methods of preparations of drug delivery systems, according to the type of IOLs presented above, were used in the literature. The preparation of drug delivery systems based on PMMA and P-HEMA IOLs was the core of our work. Those kinds of drug delivery systems have not been yet commercialized; the different past or ongoing research works dealing with the loading of IOLs will be detailed in chapter II.
Table of contents :
I. 1. Introduction
I. 2. Drug delivery systems
I. 3. Distinction between delivery systems
I. 3. 1. Distinction between delivery systems according to their physical state.
I. 3. 2. Distinction between delivery systems according to their route of administration
I. 3. 2. 1. Oral drug delivery
I. 3. 2. 2. Parenteral drug delivery
I. 3. 2. 3. Transdermal drug delivery
I. 3. 2. 4. Pulmonary drug delivery
I. 3. 2. 5. Nasal drug delivery
I. 3. 2. 6. Ocular drug delivery
1. 3. 3. Distinction between drug delivery systems according to their mechanism of drug release
I. 3. 3. 1. Immediate release
I. 3. 3. 2. Modified release
I. 3. 3. 2. 1. Delayed release
I. 3. 3. 2. 2. Extended-release
I. 3. 3. 2. 3. Pulsatile-release
I. 4. Novel drug delivery systems
I. 4. 1. Nanomaterials
I. 4. 1. 1. Polymeric nanoparticles
I. 4. 1. 2. Dendrimer nanocarriers
I. 4. 1. 3. Liposomes
I. 4. 1. 4. Nanoparticles based on solid lipids
I. 4. 1. 5. Microemulsions and nanoemulsions
I. 4. 1. 6. Carbon nanomaterials
I. 4. 1. 7. Silica materials
I. 4. 2. Ocular medical devices
I. 4. 2. 1. Microneedles
I. 4. 2. 2. In-situ gelling systems
I. 4. 2. 3. Implants
I. 4. 3. Intraocular lenses
I. 4. 3. 1. Hydrophobic acrylic lenses
I. 4. 3. 2. Hydrophilic acrylic lenses
I. 4. 3. 3. Silicone lenses
I. 4. 3. 4. Collamer lenses
I. 4. 4. Other systems
I. 5. Conclusion
References
